You are on page 1of 100

The physician may use the recommendations
confidently in caring for most patients, and is meant to
guide practices that meet the needs of patients in most but
not all circumstances. The ultimate decision must be made
by the Filipino physician and patient together, and should
not be a replacement for clinical judgment.

2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines iii

The following organizations are represented:

Voting panel:
PHA-Council on Preventive Cardiology, Council on Coronary Artery
Disease and Council on Hypertension

Philippine Society of Hypertension

Manila Doctors Hospital

Philippine Lipid & Atherosclerosis Society

Philippine College of Physicians

Food and Nutrition Research Institute –
Department of Science and Technology

Department of Health – Republic of the Philippines

Nutritionists-Dietitians Association of the Philippines

Philippine Medical Association

Las Piñas District Hospital

Philippine Society of Endocrinology, Diabetes and Metabolism

Nonvoting panel:
Philippine Health Insurance Corporation

Past Presidents and the Directors of the PHA and the offices of the
PHA President, the PHA Vice President and the PHA Treasurer

Matawaran. Te. MD Jude Erric L. MD Alex T. Oliva. MD Raul L. MD Secretary. DPA. MD Steering committee Las Piñas General Hospital Leandro C. Philippine Heart Association PHA Council on Coronary Artery Disease Helen Ong-Garcia. MD Philippine Academy of Family Physicians Technical Research Committee Cecilia Cristina Santos-Acuin. MD Elmer Jasper B. MD (PSEMD) Leisa Jeanne Rave C. MD Philippines Felix Eduardo R. Pestaño. RND. Reganit. MD Chair Philippine Society of Endocrinology. Cinco. Janetth B. Cheng. MD Adela Jamorabo-Ruiz. MD Philippine Lipid and Atherosclerosis Society Past Presidents. MD Raymund Paul C. MD PHA Council on Hypertension Vice President. Bongosia. MD Charmaine A. MD Facilitator to the Technical Research Philippine Medical Association Committee Ignacia G. Toledo Deborah Ignacia D. MD Camilo G. Granada. Leus. Diabetes and Metabolism Adriel E. MD Nutritionists-Dietitians Association of the Noemi S. MD Co-chair Non Voting Panelists Members Bien J. Matawaran. MD Paul Ferdinand M. MD Aurelia G. MSc Chair Food and Nutrition Research Institute – Department of Science and Technology Members Imelda V. Abanilla. MD Bien J. Abanilla. MD Department of Health Cecilia A.iv 2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines Voting Panelists Nannette R. Ona. Philippine Heart Association Bernadette S. MD Federick C. Gobenciong. Sison. Elisa D. Philippine Heart Association Victor L. Llanes. Baello. Gloria. Philippine Heart Association Council on Preventive Cardiology Elmer M. Jimeno. Fajardo. MD (PHA) . MD Albert Atilano. Guerrero. PhD Raymond V. Halasan. MD Philippine College of Physicians Chairman. Rey. MD Lourdes Ella Gonzalez-Santos. MD Treasurer. Reyes. Merino. MD President. Philippine Heart Association Manila Doctors Hospital Eugenio B. Punzalan. Duante. MD Rosa Allyn-Sy. Philippine Heart Association Frederick Philip B. MD Ma. MD Ms. Lazaro. Lapitan. MD (PLAS) Philippine Health Insurance Corporation Joel M. MD Carmela N. MD Jorge A. Angus. MD Jane Villaseñor-Andaman. Jr. Philippine Heart Association Romeo U. MD Orlando R. Bugarin. Serrano. MD PHA Council on Preventive Cardiology Directors. Caole-Ang. Junia. MD Joel M. MD Adriel E. MSN. RMT. Guerrero.

D.D.D. Noemi S.D. Elmer Jasper B. Philippine Heart Association Council on Preventive Cardiology Lourdes Ella Gonzalez-Santos.D. Raymond V. Deborah Ignacia D. Jimeno. M. Llanes. Oliva. M.D. M.D. Ona. Technical Research Committee Felix Eduardo R. Caole-Ang.D. Cinco.D. M. M.D. M. Chair. M. Facilitator to the Technical Research Committee . Cecilia A. Pestaño. Members. Jude Erric L. M.2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines 1 2015 Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines Adriel E. M. Technical Research Committee Imelda V. Chairman. Guerrero. M. Punzalan.

should statins be given? CQ6 Among individuals with ASCVD. should fibrates be given as an alternative to statins? CQ7 Among patients with acute coronary syndrome (ACS). should statins be recommended? CQ4 Among diabetic individuals without ASCVD. smoking cessation. weight management.2 2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines CLINICAL QUESTIONS CQ1 Among patients diagnosed to have dyslipidemia. should statin therapy be given? CQ8 Among patients with established ASCVD or diabetes. should lifestyle modifications (i.. should lipid profile determination be done? CQ9 Among patients with ASCVD. should lipid profile determination be done? Among patients without ASCVD but with multiple risk factors. should fibrates be recommended as an alternative to statin therapy? CQ5 Among patients with established ASCVD. should statin therapy be given? CQ3 Among diabetic individuals without ASCVD. should omega-fatty acids be given as an alternative to statin treatment? . regardless of their present morbid condition or risk profile.e. regular physical activity and adequate blood pressure monitoring and control) be advised to reduce overall CV risk? CQ2 Among non-diabetics without ASCVD but with multiple risk factors.

.............................. 22 Summary of Evidence................ 22 Statement 2........................................................................................ 27 Statement 5........... 19 Summary of Evidence........................................................................................................................................................ 13 Clinical Question 1.................................................. 20 Statement 1........................ 20 Summary of Evidence....................................................................................... 9 Epidemiology of Dyslipidemia in the Philippines........................................................................................ 5 Methods................. 19 Use of Electronic Cigarrettes as Alternative to Cigarrette Smoking and as a smoking cessation aid........................................................... 21 Exercise Prescription.................................................3 Exercise.........................................................................................................................................................2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines 3 CONTENTS Background....................................... 6 Clinical Outcomes..................................................................... 27 .................................................................... 24 Clinical Question 3................................................ 9 Consensus Building..................................................................... 10 CPG CQs and Recommendations.............. 27 Summary of Evidence................................................................... 25 Recommendation from Other Guidelines.................... 26 Clinical Question 4................................................................................................................................................... 18 Statement 1.................................................................................................. 25 Summary of Evidence..................................................... 27 Statement 4................................................. 25 Statement 3........................................................................................ 13 Statement 1........................... 6 Literature Search........... 23 Comparison with Other Guidelines.......... 21 Clinical Question 2....................................................... 14 Summary of Evidence.................. 8 Formulation of Recommendations.......................... 27 Clinical Question 5.............................. 7 Data Analysis...................1 Diet.....................................................2 Smoking Cessation.................................................................................................. 6 Clinical Questions................................................... 14 Addressing Malnutrition................................................................... 5 Scope of the guidelines....................................

............................................................... 30 Clinical Question 6.............................. 37 Statin-induced Myopathy............................................................................................. 42 Summary of the Evidence.................................................................................................................... 40 Statement 9............................ 48 References............... 41 Summary of Evidence. 45 HDL Lowering Therapies.......................................................................................... 45 Combination Therapies............................................................................................................. 33 Lipid Determination in Secondary Prevention............................................................. 42 Comparison with Other Guidelines.................................... 37 Clinical Question 9... 30 Comparison with Other Guidelines...................... 45 Summary of the Evidence............... 41 Use of Fibrates on Diabetic Individuals without Established ASCVD............ 31 Comparison with Other Guidelines.................................................... 40 Non-statin Therapy....................................... 31 Statement 6.................................................................. 43 Use of Omega-3 Fatty Acid.................................... 31 Clinical Question 7............................................................................................................................................................................................................................................................................................... 47 Conclusions...........................................4 2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines Statin Treatment Goal..................................... 31 Summary of Evidence........................... 74 .................................................................... 47 Limitations of the guidelines.................................................. 41 Use of Fibrates in Non-Diabetic Individuals with Established ASCVD..................... 35 Monitoring for Adverse Drug Reactions............................................................................................................................................................................ 33 Statement 8............................................................................. 55 Appendix 2: GRADE Pro Tables..... 35 Lipid Determination in Primary Prevention................................................ 34 Lipid Monitoring in Patients with Familial Hypercholesterolemia........... 31 Statement 7............................................... 32 Clinical Question 8......................................................................................................... 34 Lipid Monitoring in Diabetics in Primary Prevention............................... 48 Appendix 1: Included Studies........................................................ 47 Future Lipid Lowering Therapies......

and is meant to guide practices that meet the needs of patients in most but not all circumstances. Primary prevention refers to interventions in patients without prior coronary heart disease (CHD) or other clinical atherosclerotic cardiovascular disease (ASCVD)..e. The ultimate decision must be made by the Filipino physician and patient together. and the Philippine Society of Endocrinology. hypertension. familial hypercholesterolemia [an elevated cholesterol level > 190 mg/dL. Together with a panel of experts. the presence of xanthomas and a family history of premature cardiovascular disease]2. collaborated to develop the 2015 Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines (2015 CPG). the Philippine Lipid and Atherosclerosis Society. smoking. and Metabolism. This may influence standards and national policies for optimal patient care and cardiovascular health. and laboratory . The physician may use the recommendations confidently in caring for most patients. Primary prevention of CV events targets individuals who are considered to be at-risk including those with diabetes mellitus (DM) or multiple risk factors (i. advanced age. and should not be a replacement for clinical judgment.2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines 5 BACKGROUND The Philippine Heart Association. SCOPE OF THE GUIDELINES The scope of this CPG includes current statistics on the prevalence of dyslipidemia in our setting. and recommendations for the treatment of dyslipidemia for the prevention of CV events and mortality in Filipinos. A panel of experts in the fields of dyslipidemia. male gender. coronary artery bypass surgery or stroke before the age of 55 years in male relatives or before 65 years of age in female relatives]1. recommendations on screening and monitoring using lipid profile determination. body mass index [BMI]> 25 kg/m2. family history of premature CHD[first-degree relatives with fatal or non- fatal myocardial infarction. identification of groups at risk for cardiovascular (CV) events which will be targeted for prevention and treatment. endocrinology and clinical epidemiology were assembled to comprise the technical research committee (TRC) tasked to review available clinical evidence on dyslipidemia management. Diabetes. These guidelines are meant to update the 2005 Clinical Practice Guidelines on the Management of Dyslipidemia in the Philippines (2005 CPG). The main objective for this document is to develop clinical guidelines in the management of Filipino patients who are diagnosed with elevated cholesterol. the TRC developed specific recommendations regarding the treatment of dyslipidemia among various risk groups. coronary angioplasty. cardiology.

whenever possible. pertaining to the above 9 clinical questions. Secondary prevention refers to interventions in patients with known ASCVD in order to prevent another CV event. and left ventricular hypertrophy. To formulate the nutrition recommendations. is an update based on the combined .6 2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines findings of microalbuminuria. the Work Group used randomized controlled trials (RCTs). transient ischemic attack. intervention and outcomes for each clinical question. This CPG evaluated major classes of only locally available medications. and clinical peripheral arterial disease (PAD). and targets those with prior CHD. with the use of electronic search engines and manual search. and systematic reviews of studies carried out in adults (≥18 years of age) with or without established coronary heart disease/CVD and with or without risk factors for coronary heart disease/ CVD. Furthermore. proteinuria. nine (9) clinical questions (CQs) were prioritized and were used to provide the guidelines for the 2015 CPG (Table 1). and defined the criteria for eligible studies. the current guideline generally used the same methods as the earlier document. Several of these CQs were updates from the 2005 CPG. focusing on those that are widely used in practice. LITERATURE SEARCH The TRC searched for all published studies. clinical questions that were most relevant to clinical practice were identified. Unpublished data were also retrieved. METHODS The TRC initially reviewed the recommendations in the 2005 CPG and proposed clinical questions to be answered by the 2015 CPG. carotid artery disease. as well as the applicability of recommendations to local clinical scenarios. menopausal status. in particular. both local and international. Clinical question (CQ) 1. stroke. meta-analyses. The TRC has also identified those with acute coronary syndrome (ACS) as an important at-risk group for which a separate recommendation has been made. CLINICAL QUESTIONS The TRC developed an initial set of questions based on their expertise and from the 2005 CPG. and/or those that would provide the most benefit in terms of CV risk reduction. and diagnosed with elevated blood cholesterol. which is a significant update from the 2005 CPG. The TRC specified the population. In order to update the 2005 CPG. From the initial document.

should fibrates be given as an alternative to statins? CQ7 Among patients with acute coronary syndrome (ACS). This question still referred to the reduction in overall CV risk. should fibrates be recommended as an alternative to statin therapy? CQ5 Among patients with established ASCVD. should statin therapy be given? CQ8 Among patients with established ASCVD or diabetes. should statins be recommended? CQ4 Among diabetic individuals without ASCVD.e. smoking cessation. Assessment. CLINICAL OUTCOMES Various clinical outcomes were rated and ranked using the Grades of Recommendation.2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines 7 Statements 1 to 3 of the 2005 CPG. weight management. should omega-fatty acids be given as an alternative to statin treatment? . low-cholesterol diet.e. Other CQs are also updates from the previous guideline. Development and Evaluation (GRADE) categories of importance. regular physical activity and adequate blood pressure monitoring and control) be advised to reduce overall CV risk? CQ2 Among non-diabetics without ASCVD but with multiple risk factors. Critical appraisal of evidence was divided according to intervention (i. Clinical Questions Clinical Questions CQ1 Among patients diagnosed to have dyslipidemia.. should statin therapy be given? CQ3 Among diabetic individuals without ASCVD. should lipid profile determination be done? Among patients without ASCVD but with multiple risk factors. should statins be given? CQ6 Among individuals with ASCVD. and physical activity). Clinical Questions 8 and 9 are newly added and were deemed relevant based on the prevailing local practice of statin of high risk patients with acute coronary syndrome. The clinical outcomes were rated numerically Table 1. should lifestyle modifications (i.. low-fat. smoking cessation. should lipid profile determination be done? CQ9 Among patients with ASCVD. The use of omega 3 fatty acid is also relevant as this has been used as secondary prevention among patients with or without diabetes mellitus. regardless of their present morbid condition or risk profile.

8 2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines

on a 1-to-9 scale following the GRADE categories, where a score of
7-9 is critical; 4 -6 important; and 1- 3, of limited importance. According
to GRADE, ranking outcomes by their relative importance can help to
focus attention on those outcomes that are considered most important
and help to resolve or clarify disagreements.
The TRC designated the following outcomes to be CRITICAL with
a score of 9:
• Total mortality
• Cardiovascular deaths;
• Fatal and non-fatal myocardial infarction and
• Stroke or cerebrovascular disease.
Cardiovascular events was ranked as CRITICAL with a Score of
7. Coronary revascularization was assigned to be an IMPORTANT
outcome with a GRADE PRO Score of 6. Additional important outcomes
were added when deemed necessary for the particular clinical scenario
(e.g., angina in ACS).
Data on these six outcomes were extracted from the retrieved
studies.

DATA ANALYSIS
The extracted data from retrieved studies were pooled and analyzed
using the GRADE-PRO software. The quality of evidence and risks of
biases were also evaluated using GRADE-PRO. Evidence quality and
risk of bias were based on:
• Study design;
• Study limitations – These could include lack of allocation
concealment; lack of blinding particularly for subjective outcomes;
losses to follow-up; failure to adhere to an intention to treat analysis;
stopping early for benefit; failure to report outcomes;
• Study inconsistencies – Widely varying effects or study
heterogeneity;
• Indirectness of evidence – Applicability of the study to the
specific clinical question based on various study characteristics (e.g.,
ethnicity, choice of comparators, etc.);
• Study imprecision – Few included patients or reported events;
and,
• Other identified limiting characteristics.
Standardized summary of evidence tables was used to present the
quality of the evidence and key results in a transparent and reproducible
fashion. These are presented in the subsequent sections.
To aid in quantifying treatment effect, numbers-needed-to-treat
(NNTs) were reported in interventions with significant benefit to specific

2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines 9

Table 2. Criteria for recommendation
Quality of Outcome NNT Recommendation
Evidence
High Critical Low Strongly Recommend
Moderate Critical Low Recommend
Moderate Important Low May Recommend
Low Critical or High or not Do not recommend
important significant

outcomes. By convention, NNTs are adjusted to the local prevalence
of disease and outcomes. According to the 2008 National Nutrition
and Health Survey, the prevalence of CHD in the Philippines was
1.1%.2 This is around a third of the reported prevalence in the United
States. However, the TRC believes that the local prevalence could be
underestimated, since the NNHES definition of CHD was a diagnosis by
a physician or nurse (e.g., from a previous heart attack). Furthermore,
should a Filipino patient experience acute coronary syndrome (ACS)
and was admitted to a tertiary hospital, the mortality rate as reported by
the ACS registry is 7.8%, which is only slightly higher than the mortality
reported in the United States (6.3%).3,4 Hence, the NNTs from Western
studies were not adjusted, under the assumption that local prevalence
rates and mortality rates were not significantly different from Western
countries.

FORMULATION OF RECOMMENDATIONS
Recommendations based on the 9 clinical questions were
formulated, taking into account the following results in each summary of
evidence table (Table 2):5
• Quality of evidence for each outcome;
• Treatment effect for each outcome; and,
• Relative importance of outcomes.
With regard to the recommendation on the use of lipid profile
determination, draft recommendations were formulated so as to
facilitate the implementation of the therapeutic interventions (e.g.,
lifestyle modification, statins, and non-statins) recommended in these
2015 CPG.

CONSENSUS BUILDING
Draft recommendations were written and presented to the
members of the TRC and were subsequently modified. These guideline
recommendations were then subjected to external review by a panel

10 2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines

Table 3. Trends of Lipid Profiles of Filipinos Based on NNHeS Data
Lipid parameter Prevalence, %
2003 2008 2013
Borderline (200-239 mg/dL) to High 33.5% 41.6% 46.9%
( > 240 mg/dL) Total Cholesterol

Bordeline (130-159) to high (≥ 160 43.2% 43.2% 47.2%
mg/dL) LDL-Cholesterol

HDL-C < 40 mg/dL 54.2% 64.1% 71.3%
Elevated Triglyceride ≥ 150 mg/dL 30% 46.5% 38.6%
Reconstructed from the 2003, 2008 and 2013 FNRI NNHES data
* Based on ATP-III cut –off values

of experts representing local stakeholders in the care of dyslipidemia.
During the panel meetings, the process of guideline development and the
method for consensus building was first presented. The clinical questions
were presented to the expert panel for feedback and modification.
Subsequently, the members of the TRC presented the questions, the
answers to the question (recommendations) based on the summary of
the evidence and the GRADE table of appraisal. Comparison of the
recommendations with other guidelines was provided if applicable.
The expert panel then voted on the recommendations. Any proposed
changes to the recommendation were also voted on after thorough
discussion. The results of the panel meetings are presented here as the
final recommendations.

EPIDEMIOLOGY OF DYSLIPIDEMIA IN THE PHILIPPINES
Diseases of the heart and vascular system made up 33.0% of all
deaths in the Philippines according to the World Health Organization-
Non Communicable Diseases (WHO-NCD) Country Profiles 2014.6
Historically, based on our national surveys conducted, the prevalence of
dyslipidemia continues to increase as seen in Table 3.
In the 2008 National Nutrition and Health Survey Group (NNHeS)
report, the prevalence of coronary artery disease (CAD) in the Philippines
was 1.3%.2 The peak prevalence was noted at age group 60-69 where
5% of this age group had coronary disease. The prevalence of CAD in
rural areas was 1.0% and 1.7% in the urban areas. Moreover, based
on the ACS registry as of 2013, diabetes is considered as the second
highest risk factor among patients with acute coronary syndrome.3 The
prevalence of diabetes mellitus increased significantly from 4.8 in 2008
to 5.4 in 2013 (p=0.0336).

2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines 11 The NNHeS is a nationwide survey conducted every 5 years by the Food and Nutrition Research Institute of the Department of Science and Technology. The latest survey was conducted in 2013 and the results revealed that the overall prevalence of high total cholesterol (defined as greater than 240 mg/dL) among adults aged 20 years and above was at 46. Prevalence of high total cholesterol (>240 mg/dL) among adult Filipinos by age group Figure 2. Prevalence of high LDL-C (>160 mg/dL) among adult Filipinos by age group .8% (Figure 1). Philippine Society of Hypertension and the Philippine Heart Association. As part of the NNHeS.2%. Figure 1. with an age distribution similar to that of total cholesterol (Figure 2).9%.6% to 61.6%) higher than the national average. data on the prevalence of risk factors for non-communicable diseases are gathered. All other age groups older than this also had a prevalence ranging from 54. The overall prevalence of high LDL-C (defined as greater than 160 mg/dL) was at 47. in partnership with several government agencies and non-governmental organizations such as the Philippine Lipid and Atherosclerosis Society.7 The age group of 40-49 years was the lowest age group to have an overall prevalence (50.

• 5. the prevalence of borderline (150-190 mg/dL) to very high triglycerides (>400 mg/dL) was 38.3%. the age group of 40-49 was where the prevalence of high triglycerides began to exceed the national average (Figure 4). Finally.4% for diabetes (defined as a fasting blood sugar of at least 126 mg/dL) accelerating at age 40-49 years and peaking at age 60-69 years. The prevalences of other risk factors were as follows: • 6. • 22. Figure 3.8% for obesity (defined as a BMI of 30 or higher) and peaking at age 40-45 years. Prevalence of low HDL-C (<40 for males and <50 mg/dL for females) among adult Filipinos by age group Figure 4.6%. respectively) was very high at 71.12 2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines The overall prevalence of low HDL-C (defined as less than 40 and 50 mg/dL for males and females.3% for hypertension (defined as a systolic BP of at least 140 or a diastolic BP of at least 90) accelerating at age 40-49 years. with a relatively even age distribution (Figure 3). Prevalence of borderline (150-190 mg/dL) to very high triglycerides (>400 mg/dL) among adult Filipinos by age group . Again.

Thus. Clinical Question 1 CQ1. The TRC recommends that patients with dyslipidemia should undertake lifestyle modification regardless of their risk profile. with an inverted distribution peaking at ages 20-29 years. such as proper diet and exercise. . Six of the clinical questions were retained to answer the clinical questions. exercise and smoking. CPG CQs and Recommendations The abovementioned nine clinical questions were screened. However. there were issues on clinical questions on non-statin therapies (CQs 4. risk factors tend to surpass the national averages at the age group of 40-49 years. should lifestyle modification (i.2% for insufficient physical activity.. weight management. who are on maximally-tolerated statins and are not yet on goal. Among patients diagnosed to have dyslipidemia. Statements were constructed to answer the clinical questions and were presented to the voting panel. and 70 years and above. The panel decided which of the statements would be applicable to the Filipino dyslipidemia patients. making individuals in this age group an important lower threshold for preventive care.2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines 13 • 25. and. The section on non-statin treatment would serve as a guide for clinicians in managing their patients. researched and analyzed by the TRC. respectively.4% for smoking. has been repeatedly emphasized and been given increasing attention because of their relation to cardiovascular disease. • 45. The TRC and the voting panel decided to provide a section on the use of non-statin therapy despite the lack of clinical data. regular physical activity and adequate blood pressure monitoring and control) be advised to reduce overall CV risk? The importance of lifestyle modifications.6 and 9) so no statements were made. with a relatively even age distribution.e. the 2015 CPG has nine clinical questions but only six statements. Recommendations on adequate blood pressure control and weight loss are already documented in the guidelines of the Philippine Society of Hypertension (PSH) and Philippine Association in the Study of Overweight and Obesity (PASOO). As a general trend. smoking cessation. regardless of their present morbid condition or risk profile. Specific recommendations for this clinical question are on diet.

EMBASE. peripheral vascular events. and unplanned cardiovascular interventions like angioplasty and bypass surgery. and atrial fibrillation. and there .14 2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines Statement 1. Combined cardiovascular events included any of the following: cardiovascular deaths.770 participants. a low- fat. Validation and appraisal of the meta-analysis showed that this was of moderate methodological quality (Appendix Table 1). is RECOMMENDED. A modified fat diet aimed to include 30% or more energy from total fats. and reduce and modify fat intake. compared to a usual diet type of control. and at least partially replace the energy lost with carbohydrates (simple or complex). It included randomized controlled trials that are of high quality evidence. at any risk for cardiovascular risk. especially those with established atherosclerotic cardiovascular disease (ASCVD). cardiovascular morbidity from non-fatal myocardial infarction. Primary outcomes were total and cardiovascular mortality and combined cardiovascular events. low cholesterol diet. CVRCT Registry. The meta- analysis included randomized controlled trials that enrolled adults (18 years old or older.012 titles and abstracts which were initially scanned for review. protein or fruit and vegetables. which included 60 comparison arms and 71. of which a total of 48 randomized controlled trials were included in the review.1 Diet For individuals at any level of cardiovascular risk. pregnant or lactating were excluded in the studies. A low fat diet aimed to reduce fat intake to less than 30% energy from fat. CAB Abstracts. SIGLE. and included higher levels of mono-unsaturated or poly- unsaturated fats than the “usual diet”. stroke. heart failure. These interventions included an intention to reduce total fat intake. Low cholesterol was pegged at 150 mg/1000 kcal. The meta-analysis did a comprehensive search of articles published from March 1998 up to June 2010 using the Cochrane Library. such as would be expected to result in improvement of serum lipid profile. no upper age limit). Summary of Evidence The basis for reducing or modifying fat in the diet was an updated meta-analysis of forty-eight (48) randomized controlled trials8. There were no other large clinical trials that were published from 2010 onwards that could be included in this review. MEDLINE. The search resulted in 22. although those who were acutely ill. rich in fruits and vegetables. Participants were of any gender. modify fat intake. bibliographies and experts. angina. The intervention was reduction or modification of dietary fat or cholesterol.

reducing them by 14% (relative risk 0. This was given a grade of moderate because some of the studies included in the review did not report any cardiovascular events. Ten of the comparison arms included only people at high risk for cardiovascular disease. 95% CI 0.84-1.00. 1. 627 participants.04. The protective effect was seen in patients who continue to modify their diet over at least two years. I2=0%. is protective from the development of the composite outcome of major cardiovascular events. 14 only women.2 to -1. The importance of this result should allow physicians to give dietary advice of reduction of saturated fats to patients who are at high risk of cardiovascular disease and should be stressed that this should be a sustained pattern of eating. but not in women or in combined studies of men and women. through reduction and/or modification of dietary fat. reduction or modification of fat diets showed no statistically significant effects on overall mortality (RR 0. there was no clear effect on serum HDL . Studies in community settings also reduced cardiovascular events if given the low fat/modified fat diet. 2. 95% CI 0. I2 0%) and fasting serum triglycerides (MD -23. and 30 comparison arms were both men and women. Generally.86. I2=0. the quality of the evidence ranged from moderate to high. the quality of the evidence for two outcomes were graded low as some of the clinical trials included in the analysis were not blinded with different levels of attention and support to the intervention group.9 mg/dL. The studies in the meta-analysis also showed a modest reduction in the serum total cholesterol (mean difference=-10. Reduction of dietary saturated fats.The intervention reduced the CV events in men.978 participants. serum LDL cholesterol (mean difference=-8.609 participants and I2 of 50%.2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines 15 is certainty in the benefits of the treatment arms and control arms. However. n=65. However.98. 95% CI -13.94. n=71.96) based on 24 comparison arms with 65. and 33 at low risk. It was also noted that there were fewer than 1.54.93-1.1 mg/dL.1. 218 participants.000 events in total so there is limited power to estimate the effect. 95% CI -18. I2 0%). Three studies were conducted in Australia/ New Zealand. I2 51%).1 mg/dL. For the primary outcomes. and one study was conducted in the Middle East.0%.04.131 participants.77 to 0. However. 4292 deaths) or cardiovascular mortality (RR 0. Sixteen comparisons included only men. None of the randomized controlled trials were done on Filipinos as subjects. with Caucasians comprising most of the study subjects. 95% CI -46. 17 were at moderate risk.5 to -3. 95% CI 0. there was no cost analysis study conducted in the analysis and there were questions of directness to our population.9 to -0. Most of the studies were conducted in North America.790 participants.407 cardiovascular deaths) compared to usual diet.

particularly heart healthy diets. The International Atherosclerotic Society10 released a position paper recommending a reduction of saturated fat in the diet to <7%. It was advised in the FNRI food pyramid to increase fat intake by adding .04) Fatal and non. the Food and Nutrition Research Institute (FNRI) has developed a food pyramid.1. However. The latest guidelines from the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines9 emphasized that lifestyle modification.89.98 NS (0.86 (0.94 NS Deaths (0.11) Cardiovascular Moderate 7 2867/37402 2020/28106 0. Based on the food pyramid. the trials showed no clear benefit on overall mortality and cardiovascular mortality.93. Reduction or modification of dietary fat may be protective of cardiovascular events.85.16 2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines Table 4. decreasing trans fat by 1%.77.1.96) Revascularization Moderate 6 NS NS NS NS cholesterol.11 Simple Dietary Plan for Fat Modification In the Philippines. which is a simple and easy to follow daily eating guide and is based on the daily food intake of Filipinos. and dietary cholesterol to < 200 mg/day of the daily total calorie intake. remains a critical component of health promotion atherosclerotic cardiovascular disease. NS and nonfatal) 1. High 9 1174/37280 894/27611 0. both prior to and in concert with the use of cholesterol-lowering therapy.1. accounting for the low calorie intake. 209 events 0. and triglycerides. with a decrease in levels of total and LDL cholesterol. Table 4 summarizes the results of the review and the relevant outcomes.99 (0. A comprehensive list of food menu was published in the 2005 Philippine Practice Guidelines.04) Cardiovascular High 9 774/37840 633/28138 0. This is similar to the recommendations of the National Institute for Health and Care Excellence of the United Kingdom 2014.11) Strokes (Fatal High 9 683/34790 457/25063 0.9 NS fatal MI (0.72. Summary of evidence on the effects of dietary modification Outcome Evidence Relative Overall Overall Relative NNT Quality Importance Control Rate Treatment Risk Rate Total Mortality High 9 2404/40957 1888/30833 0. the total fat intake is only 15% of the total caloric intake.

kamote. the FNRI released a simpler version of the food pyramid.2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines 17 margarine or butter in the diet. It is advised that half of the plate is composed of green leafy vegetables and one serving of fruit per meal.500 calories per day. Figure 5.200 to 1. which they termed as “Pinggang Pinoy”or “Pinoy Plate” (Figure 5 and Table 5). and distributing foods proportionally among the food groups provides approximately 1. gabi.. and some of the invisible oils found in fruits and nuts. kamoteng kahoy. ubi) . It serves as a reminder to Filipinos on how to fill up their plates properly. It used a science-based approach with the best scientific evidence and compliments and supplements the food pyramid of the FNRI. Guide to serving portions Rice and alternatives 1 serving of any of the following: • 1 cup cooked rice • 4 pcs of pandesal (17 g each) • 4 slices of loaf bread (17 g each) • 1 cup of cooked macaroni or spaghetti noodles • 1 piece of root crop (e. A nine-inch plate is advised. Pinggang Pinoy Table 5. In 2014. 4 to 6 servings are encouraged per day.g. For fruits.

where the prevalence can exceed 70%.g.. watermelon. even among adults. of small fish (e. Data from the Food and Agriculture Organization reported that 17% of Filipino adults are underweight for age. beef or pork) • 1 pc.. kaymito) OR • 1 slice of big fruit (e. Of small chicken leg or 1 matchbox size of chicken breast • 1 matchbox size of meat (e.. galunggong) • 1 pc. banana.13 Malnutrition in these patients . of small chicken egg Vegetables • ¾ to 1 cup of cooked or raw vegetables Fruits 1 serving of any of the following: • 1 medium-sized fruit (e.. dalanghita.12 Malnutrition is also a major problem among certain patient subgroups.18 2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines Fish and alternatives Two servings of any of the following: • 1 pc. papaya) Water and beverages 8 or more glasses of water daily Addressing Malnutrition Malnutrition due to low caloric and low protein intake is an important public health problem in the Philippines.g.g. such a chronically ill patients.g.

All three trials looked at primary prevention outcomes. Therefore.14-16 The interventional group had an intensive treatment program for smoking cessation. RR 0. Generally. 0. The clinical trials included in the CPG are seen in the appendix. and acute major CV events (N=18. Only one trial looked at secondary outcomes such as MI and stroke. which include behavior modification and may use devices such as nicotine gum or patches. MRFIT and OSLO study included men with multiple risk factors.5). and the former outcome showed a trend in favor of cigarette cessation. regardless of nutritional status. In underweight patients. when accurate dietary advice is sought.1%) are overweight or obese.85 [95% CI 0. Statistically significant results are seen in the total mortality (N=18. Two clinical trials. majority of the caloric intake comes from carbohydrates and proteins to ensure low fat intake. Dietary advice should ensure that patients. Two of the studies looked at multiple risk factors. it is important to perform an overall assessment of nutritional status in patients when advising about dietary changes. The studies were all .99)]. while the last one also included respiratory and cancer outcomes. Table 6 summarizes the review and relevant outcomes. do not predispose the patient to caloric and protein malnutrition.355 clinical trials on smoking cessation but.76.90 [95% CI 0.82. cigarette smoking cessation is STRONGLY RECOMMENDED.2 Smoking Cessation For individuals at any level of cardiovascular risk. only three (3) trials had relevant outcomes and were thus included.023.0%) adults have chronic energy deficiency (CED. such as diet and smoking cessation. the quality of the evidence is moderate with the downgrade due to the question of directness. Summary of Evidence Randomized controlled trials on smoking cessation and their effect on cardiovascular morbidity and mortality were included in the review for this recommendation.023. A referral to a nutritionist or dietitian is recommended in all patients.2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines 19 adversely diminish outcomes. RR 0. while the Lung Health Research Study Group had both men and women in the study. while three out of ten (31. Data from NNHeS showed that one out of ten (10. BMI <18. even those with evidence of cardiovascular disease. The GRADE balance sheet seen in the appendix combines the appraisal of the studies included in the guideline recommendation with the outcomes. There was a trend towards benefit of cigarette cessation in CV mortality. Statement 1. There are 1. 0.95).

the health effects of these devices are not known considering the lack of studies. Thus. 1. adequate exercise is RECOMMENDED.99] 1000 (9. 1. However.791 0.90 [0.866 1. total cigarette smoking cessation is recommended to patients with all levels of CV risk factors.76. and Asians. In conclusion.82.92 [0. Exercise For individuals at any level of cardiovascular risk. while carcinogens and other toxic chemicals at low levels were detected in the vapors. Statement 1.76.8) Cardiovascular 2 fewer per 2 16.07] myocardial infarction Cardiovascular 10 fewer than 3 18.20 2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines Table 6. PCCP does not support the use of these devices as smoking alternatives or cessation aids until long-term efficacy and safety data have been reported.866 0.95] events 1000 (100) Stroke NS 1 12.81] done in Caucasian populations.80. 1.92 [0.023 0.023 0.79. .20 [0. 95% CI) 102 fewer per Total Mortality 3 18. 0.17 Furthermore. These products deliver doses of nicotine or non-nicotine vapors to the respiratory system without the need for combustion of tobacco. in particular Filipinos were not part in these trials.12] deaths 1000 (500) Fatal and nonfatal NS 1 12. Summary of evidence on the effects of smoking cessation Outcome Studies Participants Effect Estimate NNT (RR. a position statement issued by the Philippine College of Chest Physicians (PCCP) highlighted that there is profound lack of evidence on the effectiveness of electronic cigarettes as a tool or aid to smoking cessation. Use of electronic cigarettes as alternative to cigarette smoking and as a smoking cessation aid Electronic cigarettes are a form of Electronic Nicotine Delivery Device. 0.3.85 [0.

to high-intensity exercise per week.17] Summary of Evidence Literature review revealed 48 articles that evaluated the benefit of exercise on the risk of cardiovascular outcomes. The lack of randomized controlled trials was mostly attributed to poor long-term adherence to exercise programs. triglycerides by 0. and increase HDL-C by 0. the Chengdu trial. exercise of approximately 150 minutes of moderate.23%.305 0. Additionally.05] Cardiovascular 2 5.305 0.88 [0.18-22 In general. Thus. 150 minutes per week should be cumulated from around five sessions per week with . with an NNT of 48.62. Summary of evidence on the effects of exercise Outcome Studies Participants Effect Estimate NNT (RR.2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines 21 Table 7.29 [0. One way to achieve this is to explain that the time allotted per week should be split into several exercise sessions. Thus. only a few studies evaluated hard cardiovascular outcomes.305 0.45%.75 [0. the STENO2 trial. these studies recommended approximately 150 minutes of moderate. 1. In this case.09] mortality MACE 2 5. Pooled analysis revealed that such an exercise regimen reduced major acute coronary events by 25%. 95% CI) All cause mortality 2 6. 0.02%. Mostly were observational and cohort studies. Furthermore. Exercise prescription Compliance is one of the major difficulties when prescribing exercise to patients. and the study by Fowler and colleagues (2002). 0. 1.67.85. and non-fatal myocardial infarction by 71% (Table 7). exercise was found to marginally reduce LDL-C by 0. 1.86. It is important to highlight that consistency and regularity are important so that exercise becomes an integral part of a patient’s lifestyle.76] 7 infarction Stroke 2 5.to high- intensity exercise per week is recommended in individuals to improve patients’ outcomes.95 [0.11.027 0. only four studies were included in the analysis: the LOOK Ahead trial.97 [0.91] 48 Non-fatal myocardial 1 160 0. Quality of evidence for the important outcome of major adverse cardiovascular events was moderate.

statins are RECOMMENDED for the prevention of cardiovascular events. should statin therapy be given? This clinical question aims to give guidance to the use of cholesterol- lowering treatment for primary prevention in patients with several cardiovascular risk factors.22 2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines a duration of 30 minutes. Examples of exercises may include swimming. Furthermore. smoker. they should not be experiencing symptoms such as chest pain. Among non-diabetics without ASCVD but with multiple risk factors. proteinuria. However. *Risk factors are: male sex. cycling. postmenopausal women. Clinical Question 2 CQ 2. and left ventricular hypertrophy. If assessment reveals that a patient is physically incapable of safely performing moderate to intense exercise. hypertension. but may be inadequate in intensity as the patient becomes physically stronger. microalbuminuria. physical activity may be integrated into their daily routine. sports activities. or dizziness/syncope. dancing. A general rule is that they should have difficulty speaking during the exercise. Slow exercises such as yoga or tai chi may improve strength and flexibility. These risk factors were identified based on the clinical trials reviewed for the CPG. stair-climbing. brisk walking. without atherosclerotic cardiovascular disease. It is important to specify that the patient should exert moderate to intense activity during exercise. such as climbing of stairs or brisk walking. refer the patient for physical rehabilitation and strengthening to a qualified physiatrist. and supervised aerobic exercise programs. *Patients who fulfill the criteria for the diagnosis of familial hypercholesterolemia (see statement 6 on screening and lipid monitoring for familial hypercholesterolemia) should be initiated therapy for aggressive LDL-C lowering . This will also ensure that the exercise sessions do not interfere with a person’s daily routines. Statement 2 For non-diabetic individuals aged ≥ 45 years with LDL-C ≥ 130 mg/ dL AND ≥ 2 risk factors*. family history of premature CHD. The physician should assess the functional capacity and overall risk of patients before prescribing exercise. BMI > 25 kg/m2. jogging. difficulty of breathing. at the same time.

myocardial infarction (MI) by 39%. All the outcomes were deemed critically important except for coronary revascularization. respectively. The average reductions in TC and LDL. the incidence of a myocardial infarction increased as well. These trials enrolled mostly men with at least 1 other risk factor. the TRC agreed that if an individual has 2 or more risk factors. Lipid profile determination was repeated after 3 months and was done yearly until the end of these studies. stroke by 26%. All of these trials either used total cholesterol (TC) and/or LDL-C as part of their inclusion criteria.23-29 Trials whose entry criteria included the presence of diabetes mellitus were evaluated in a different subgroup. Even if MEGA and ASCOT-LLT. with the exception of the MEGA study.30 Therefore. statins in individuals without ASCVD showed a significant reduction in all-cause mortality by 19%. cardiovascular death by 33%. which were 168 mg/dl for TC and 94 mg/dL for LDL-C. The quality of evidence was mostly moderate owing to indirectness in the enrolled population which mostly included Caucasians. which enrolled Japanese patients (Appendix 1 Table 1. with a minimal number of diabetics evenly distributed in both arms (with the exception of the MEGA and ASCOT-LLT which have 21% and 24% diabetics. A total of 7 RCTs were included. respectively) (Appendix 1. which have a modest number of diabetics. which was important since it is an outcome least likely to happen if these . cardiovascular (CV) events by 27% and coronary revascularization by 29% (Table 8).4). were excluded from the analysis.4). as the number of risk factor increases in an individual.C in the clinical trials were 20% and 29%. The average age of the trial participants was 58 years old with a range of 44 -71 years of age. The evidence on cardiovascular events as an outcome was graded as low due to its issue of inconsistency with a large I2 of 59% (this could be due to CV events being a secondary outcome in all the trials with the exception of AFCAPS/TexCAPS). statin is recommended due to the fact that there were significant reductions in the pre-specified outcomes. all of these outcomes remained significant. with the lowest levels seen in the JUPITER trial. Based on the INTERHEART study. As for the desired outcomes.2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines 23 Summary of evidence Randomized controlled trials (RCT) evaluating statins in individuals without atherosclerotic cardiovascular disease (ASCVD) with at least a minimum duration of one-year follow-up were reviewed for this clinical question.

24 2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines

Table 8. Summary of Evidence on Treatment Effects of Statins in
Primary Prevention.
Outcome Studies Total Effect Estimate NNT
Participants (RR, 95% CI)
Total Mortality 4 42,534 0.81 (0.72-0.90) 167
CV death 7 50,450 0.67 (0.57, 0.79) 250
MI 7 50,450 0.61 (0.54, 0.70) 111
Stroke 6 43,845 0.74 (0.63, 0.88) 250
Cardiovascular 4 42,544 0.73 (0.67, 0.79) 56
events
Coronary 4 49,586 0.71 (0.65, 0.78) 100
Revascularization

individuals were treated optimally.
The TRC and Voting Panel decided to implement LDL-C and age
cut-offs to better target patients who have no evidence of atherosclerotic
disease but would benefit from statin therapy.
The LDL-C level chosen was from the ASCOTT-LLT trial, where
patients had a mean LDL-C of 131.3 mg/dL to represent patients
at higher risk of development of cardiovascular outcomes in light of
additional risk factors.
The recommended cut-off age of 45 years old was on the basis of the
epidemiology of dyslipidemia among Filipinos and the age consideration
of patients in the different primary prevention trials appraised. Forty-five
years was decided to be the representative age at which patients with
multiple risk factors for development of atherosclerotic cardiovascular
disease would benefit from statin therapy.
Lastly, the primary prevention trials on statins only included patients
with at least 2 risk factors. The TRC was not able to find data on patients
with one or no risk factors. Hence, the TRC recommendations only
encompass patients with 2 or more risk factors. It should be emphasized
that although the TRC has no recommendations for patients > 45 years
with less than 2 risk factors, individuals in this group are still eligible for
lifestyle interventions, as discussed in the previous section.
Thus, the use of statins for primary prevention of ASCVD is
recommended for patients aged 45 years and above with 2 or more risk
factors.

Comparison with other guidelines
The 2014 ACC/AHA guidelines recommend the initiation of statin

2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines 25

therapy for primary prevention in the following patient groups: 1)
individuals ≥21 years of age with LDL-C ≥190 mg/dL to achieve at least
a 50% LCL-C reduction; 2) all diabetic patients; and 3) patients with
more than 7.5% risk for development of ASCVD based on the ACC/AHA
cardiovascular risk calculator (provided with the published guidelines).9
In contrast, the 2011 ESC guidelines recommend the use of statins to
treat hypercholesterolemia to a level dictated by the patient’s calculated
risk score using the Systematic Coronary Risk Evaluation (ESC SCORE)
risk charts.31 Unfortunately, there is no local risk scoring that has been
developed for Filipinos to determine the risk for development of ASCVD,
and studies on the applicability of other risk scoring systems on Filipinos
have not been done.

Clinical Question 3
CQ 3. Among diabetic individuals without ASCVD, should statins be
recommended?

Statement 3
For diabetic individuals without evidence of atherosclerosis
(ASCVD), statins are RECOMMENDED for primary prevention of
cardiovascular events.

Summary of the evidence
Evidence on the use of statins for primary prevention of
cardiovascular outcomes were derived from 8 different clinical trials. In
the original guideline published in 2005, only 5 studies were included;
this has been updated in the current recommendation.
Of the eight studies that were included, five were sub-studies from
a larger group of individuals who had no previous cardiovascular events
(AFCAPS/TEXCAPS, ALLHAT-LLA, ASCOT-LLA, PROSPER, MEGA)
while the other three were primarily studies done on individuals with
diabetes (ASPEN, CARDS, HPS).25,26,32-37 Whenever a study involved
a combination of patients for primary and secondary prevention, then
only the data for primary prevention was obtained and analyzed (e.g.,
ASPEN).
Appendix 1 Table 1.4 summarizes the characteristics of the studies
that were included in this review. Different statins of various daily doses
were used including lovastatin 20-40 mg, pravastatin 10-20 and 40 mg,
atorvastatin 10 mg, and simvastatin 40 mg. The baseline lipid values
also varied across the studies with the mean baseline total cholesterol
ranging from 195 +31 to 227 +33.8 mg/dL; and the baseline mean
LDL-C ranging from around 115 +26.6 mg/dL to a high of 150 +31 mg/

26 2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines

Table 9. Summary of Evidence on Treatment Effects of STATINS in
Diabetic Individuals without ASCVD
Outcome Studies Participants Effect Estimate NNT
(RR, 95% CI)
Total Mortality 1 2,837 0.73 (0.53,1.010) Ns
Fatal CHD/CV death 3 7,544 0.98 (0.68, 1.41) Ns
Fatal & Nonfatal MI 4 27,810 0.73 (0.64, 0.83) 100
Stroke 4 27,810 0.75 (0.63, 0.89) 200
Cardiovascular 8 16,095 0.78 (0.70, 0.86) 45
events
Coronary 3 25,783 0.84 (0.73, 0.97) 200
revascularization

dL. The studies included both genders, and the age range for most of the
studies is from 45 to late 70’s, with the PROSPER study being specific
for elderly 70-82 years.
Table 9 summarizes the results of the review and the relevant
outcomes. Statistically significant results are seen from the outcomes of
fatal and nonfatal MI (N=27,810, RR 0.73 [0.64, 0.83]), stroke (N=27,810,
RR 0.75 [0.63, 0.89]), acute major CV events (MACE) (N= 16,095,
RR=0.78 [0.70, 0.86]) and coronary revascularization (N=25,783, RR=
0.84 [0.73, 0.97]). A trend to benefit is seen for the outcomes of total
mortality, and CV death. Significant impact on clinical outcomes was
achieved using even low to moderate intensity statins.
The GRADE balance sheet combines the appraisal of the studies
included in the guideline recommendation with the outcomes. Generally,
the quality of the evidence is moderate with the downgrade due to
the question of directness. The studies were all done in Caucasian
populations and Asians, and in particular Filipinos were not included in
the samples that were included in these trials. Likewise, 5 out of the
8 studies were subgroup analysis of diabetic individuals from a larger
group of individuals with no previous cardiovascular events.
Thus, the recommendation is only moderate for the use of statins for
primary prevention in diabetic individuals without ASCVD.

Recommendation from other guidelines
Other guidelines have similar recommendations but add on a layer
of risk on top of diabetes mellitus. For example, the Canadian Diabetes
Association guidelines recommend statin therapy for diabetic individuals
with an indication for lipid-lowering therapy.38 The American Diabetes

and 6% had left ventricular hypertrophy. The recommendations in this local guideline is to give statin therapy for ALL adult diabetic individuals for primary prevention especially among those with Type 2 diabetes mellitus. should fibrates be recommended as an alternative to statin therapy? Statement 4 See section on non-statin therapy Clinical Question 5 CQ5. should statins be given? Statement 5 For patients with established atherosclerotic cardiovascular disease (ASCVD). as well as various CV risk factors are prevalent even among newly diagnosed diabetics. and 80% of all subjects had LDL-c of at least 100 mg/dL.39. or for those who are at least 40 years old and with additional CV risk factors (total of 3 risk factors: > 40 years old.2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines 27 Association on the other hand recommends high-intensity statin for patients of all ages with diabetes and overt CVD. It is silent though for diabetic individuals who are less than age 40. Clinical Question 4 CQ 4. Among diabetic patients without ASCVD.39 Those who have diabetes and are aged 40-75 years old should consider using moderate-intensity statins. For example. Hypertension was found in 42% of individuals with a mean BP of 144/88 mm Hg. 3% had ischemic changes. Summary of the evidence Evidence on the use of statins for the secondary prevention of cardiovascular outcomes were derived from 18 clinical trials comparing statins against placebo in secondary prevention populations. The justification for this recommendation is the frequent observation that both macrovascular and microvascular complications.45 The electrocardiographic findings showed that 2% had myocardial infarcts. with another 38% with elevated triglyceride of at least 150 mg/dL. the CANDI Manila study among newly diagnosed adults with type 2 diabetes mellitus (mean age of 50 years) demonstrated a high prevalence of diabetic complications and CV risk factors. without regard for age nor duration of diabetes. diabetes and another CV risk factor).41-59 . statin therapy is RECOMMENDED. Among patients with established ASCVD.

75) and stroke (RR 0.78 (0.166 0. 95% CI 0.67. The baseline lipid levels in the included studies varied.91) 16 CV Events Myocardial 5 1.78.091 0.53 – 1.87. 95% CI 0.67 (0.5mg/dL. pravastatin 20 to 40 mg.351 0.91) 67 Mortality CV death 14 59.73 (0.84). cardiovascular mortality (RR 0. 95% CI 0.66 – 0. Summary of Evidence on treatment effect of statins for secondary prevention Outcome Studies Total Effect Estimate NNT Participants (RR. and simvastatin 10 to 40 mg. 95% CI) General population All cause 15 60.78 (0. For those with DM.79 – 0.75- 0.33. to 83 for stroke (Table 10).28 2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines Table 10.85 (0.0 mg/dL to 387. .87 (0.00) NS infarction Stroke 5 2.91).70. 95% CI 0.79. fluvastatin 80 mg.14) NS mortality Five studies assessed the use of statins for secondary prevention in individuals with type 2 diabetes.75) 45 infarction Stroke 11 52.49 – 0. statin therapy is recommended. myocardial infarction (RR 0.79 (0.90) (Table 10).79 – 0. which includes the following statins.66-0.90) 37 All-cause 5 707 0.84) 62 Myocardial 13 54.5 summarizes the characteristics of the studies that were included in this current guideline.83-0.84) 83 Patients with diabetes Major Adverse 5 4.370 0.72 – 0. Statin preparations available locally were the only ones included in the review. with the mean baseline LDL-C ranging from 199.75 – 0.72-0. in patients with ASCVD. The studies included both genders.91) and stroke (RR 0. Hence. statistically significant results are seen for the outcomes of MACE (RR 0.3+39.60-63 Appendix 1 Table 1. atorvastatin 10 to 80 mg.426 0. 95% CI 0.83 – 0.53 – 1.70 (0.84).018 0.49 – 0.949 0. with NNTs ranging from 45 for myocardial infarction.85. 95% CI 0. Statin treatment in those with ASCVD resulted in a statistically significant reduction in the critical outcomes of total mortality (RR 0.1+73.

Analysis of the evidence on high-intensity vs moderate intensity statin therapy using GRADE Pro showed that the quality of evidence is moderate. J Formos Med Assoc 2002(superscript 67). TNT (2005) and IDEAL (2005) clinical trials. The evidence was able to show a net benefit favoring high-intensity statin therapy in reducing the critical outcome of myocardial infarction (RR 0.2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines 29 Table 11. There are some evidences that Asians may require a lesser *According to a study by Wu.8) that compared varying statin regimens: Armitage et al (2010). and less on the drug dose used. Ator 20 mg can reduce LDL by 42. Evidence on the appropriate statin intensity for secondary prevention in individuals with ASCVD were obtained from 4 trials (Appendix 2 Table 2.30% Fluvastatin 20-40 mg Pravastatin 5-40 mg Simvastatin 10 mg Moderate intensity 31% . Phase Z of the A-Z trial(2004). Circulation The GRADE balance sheet for the appraisal of evidence on the use of statins in secondary prevention among patients with ASCVD and DM showed that the quality of evidence is moderate for both subgroups. Filipinos where not well represented in the clinical trials. particularly Filipinos.40% Atorvastatin 10 mg Fluvastatin 80 mg Rosuvastatin 5-10 mg Simvastatin 20-40 mg High intensity >40% Atorvastatin 20*-80 mg Rosuvastatin 20-40 mg Note: Modified from Stone et al: 2013 ACC/AHA guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults.5% in Asians. 95% CI 0. Heterogeneity of pooled studies also resulted in serious inconsistencies and a further downgrade of the evidence. including Filipinos .78-0. Statin treatment intensity Treatment intensity % LDL-C reduction Drug regimen Low intensity 20% . It should be emphasized that the definition of statin treatment intensity rests on the degree of LDL-C reduction. compared to low intensity statins which reduces LDL-C by 20- 30%. High intensity statins reduce LDL-C by >40%.63-66 These abovementioned studies compared high intensity (atorvastatin 80 mg or simvastatin 80 mg) to medium intensity (atorvastatin 10 mg or simvastatin 20 mg) statins. Asians. et al. with quality downgrade due to the question of directness.92).85. were not well-represented in these trials. The studies included were all performed on Caucasian populations. and were mostly done in Caucasians. with the quality downgrade resulting from questions of directness. This updated guideline recommends that high-intensity statin therapy be used in secondary prevention of patients diagnosed with ASCVD.

68 Treatment is focused on achieving target serum lipid levels.9 Moderate- intensity statin therapy is indicated only in those who cannot tolerate high-intensity statin therapy. reduced LDL-C levels by 34. and using high dose statins may lead to higher risk of developing adverse drug reactions.g.31 The 2012 Canadian Cardiovascular Society guidelines likewise recommend statins for those with high risk (e. however..8% and 42. as adapted by some international guidelines. and dose is adjusted accordingly to this end. . Needless to say. The 2011 European Society of Cardiology (ESC) guidelines on dyslipidemia recommend statins at the highest tolerable dose as part of the interventions for patients with very high cardiovascular risk.30 2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines dose to achieve target LDL-C goals. Statin Treatment Goal In general.67 Thus. including those with established cardiovascular disease. there is a need to conduct a bigger clinical trial for Filipino patients. On the other hand. unless contraindicated. that physicians use appropriate statin dose that will achieve the needed treatment reduction goal but will also minimize the risk of adverse events. the 2015 CPG recommends a 30% or greater reduction in LDL-C for appropriate treatment goal with statin therapy. Comparison with other guidelines Several international guidelines have their own recommendations for managing patients with established ASCVD.vs high-intensity statin therapy have shown a dose- dependent response in terms of benefit in the reduction of adverse outcomes. However. the sample size is small. a treatment goal LDL-C level of < 70 mg/dL may be recommended. the 2013 American Heart Association/American College of Cardiology (AHA/ ACC) guidelines recommend that high-intensity statin therapy should be initiated or continued as first-line therapy in those 75 years of age or younger who have clinical ASCVD. for purposes in clinical practice. those with clinical vascular disease or those with Framingham Heart Risk score >20%).5% respectively. Judicious use of statins after consideration of benefits and risks is recommended for those with clinical ASCVD aged over 75 years. as trials on moderate. we also recommend to individualize treatment in patients who may develop intolerance to high dose statins. One trial looking at the efficacy of simvastatin and atorvastatin 20 mg once daily. which included Filipinos. The TRC decided to retain the table on statin intensity to be used for Filipino patients for secondary prevention (Table 11) and LDL-C reduction as applicable to our population.

This new guideline statement focuses on the timing of initiation (or continuation) of statin therapy among patients diagnosed with acute coronary syndrome (ACS). ten trials were adjudicated to be included in the analysis of initiation of statins falling within the first 5 days after an acute coronary event and that total mortality. major cardiovascular events. and stroke are reported. and FACS.69-77 Table 12 summarizes the results of the review and the relevant outcomes. PACT. PTT. when initiated early within 5 days of ACS. These ten trials are A to Z.2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines 31 Clinical Question 6 CQ 6. early high-intensity statin therapy is RECOMMENDED and should be continued when already on statin therapy. cardiovascular death. myocardial infarction. should fibrates be given as an alternative to statins? Statement 6 See section on Non-statin therapies. MIRACL.64. LAMIL. should statin therapy be given? Statement 7 For individuals with acute coronary syndrome. Early intervention is advocated to optimize recovery and minimize complications. A trend to benefit was seen for the outcomes of non-fatal myocardial infarction and revascularization. LIPS. cardiovascular deaths. Among randomized controlled trials on early statin therapy for acute coronary syndrome. stroke and major cardiovascular events. PAIS. Among patients with ASCVD. Clinical Question 7 CQ7. ESTABLISH. The adage “time is muscle” is based on the principle of the necessity for immediate action during the golden period in which myocardial ischemic damage is still potentially reversible or myocyte necrosis can still be contained and much of the myocardium in the ischemic penumbra can still be salvaged. results in fewer total deaths. CV death. Statistically significant results are seen from the outcomes of total mortality. Summary of Evidence Timing of therapy is critical among patients with acute coronary syndrome. with a . Among patients with acute coronary syndrome (ACS). This pooled analysis shows that statins. Musashi-AMI. revascularization. stroke and major cardiovascular events.

the quality of evidence was low due to downgrading for directness and inconsistency (I2=60).70 (0.58-0.88 (0.08 NS Stroke 10 13.94) 110 CV death 8 10. i.50-0. Summary of Evidence in the use of statins in Acute Coronary Syndrome Outcome Studies Participants Effect Estimate NNT (95% CI) Total Mortality 10 13.74 (0. and Filipinos were not well represented.94) 43 event Revascularization 10 13. The quality of evidence of some studies is moderate based on the GRADE Pro Evidence Table (Appendix 2 Table 2.707 0.95 (0.99) 227 Cardiovascular 10 13. Considering the severity of acute coronary syndrome and the dose-dependent effect of statins.80 (0. Thus.86-1.11) with the downgrade due to the question of directness.707 0. For non-fatal myocardial infarction and revascularization. Comparison with other guidelines Published guidelines on the diagnosis and management of acute coronary syndrome incorporate general assertions with respect to the temporal aspects of statin therapy.67-0.707 0. the quality of the studies was low due to the question of directness and imprecision (wide confidence interval). In the 2014 version of the Philippine Heart Association Clinical Practice Guidelines for the Diagnosis and Management of Patients with Coronary Artery Disease.465 0. starting statins is strongly recommended for all patients with Non-ST elevation acute coronary syndrome. The Musashi-AMI and ESTABLISH trials were carried out in a Japanese population.94) 125 Non Fatal Mi 10 13. high-intensity is recommended in this extremely high-risk group.06) NS trend towards reduction of myocardial infarction.707 0. and revascularization.81-1.93 (0.e. For major cardiovascular events.32 2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines Table 12. three statements were made: 1) high-dose statins are recommended during the first 24 hours of admission.82-0.78 For those with ST Elevation Acute Coronary Syndrome. these studies included Caucasians. statin therapy is recommended with low to moderate level of evidence for improving critical outcomes.707 0. in patients with atherosclerotic cardiovascular disease. 2) atorvastatin or rosuvastatin are recommended during the early phase of therapy up .

the use of lipid profile for screening is RECOMMENDED. initiation or continuation of high- intensity statin therapy is a class I recommendation but with Level of Evidence B. * Risk factors are: male. Comparing the local guidelines to the 2014 AHA/ACC Guideline for the Management of Patients With Non–ST-Elevation Acute Coronary Syndromes. initiation or continuation of high-intensity statins is a Class I Recommendation with Level of Evidence A. should lipid profile determination be done? Statements 8 For individuals with evidence of ACSVD or diabetes.80 These aforementioned guidelines are congruent and clearly advocate for the early initiation or maintenance of statin therapy across the spectrum of acute coronary syndrome. For individuals without evidence of ASCVD but aged > 45 years AND with 2 or more risk factors*. and 3) high-dose rosuvastatin (20 to 40 mg) or atorvastatin (40 to 80 mg) therapy is recommended before emergency percutaneous coronary intervention. Among patients with established ASCVD or diabetes. should lipid profile determination be done? Among patients without ASCVD but with multiple risk factors. postmenopausal women. the use of the lipid profile is RECOMMENDED for monitoring of treatment response since ALL patients with ASCVD should be on lipid-lowering therapy. monitoring the response to both pharmacologic and non-pharmacologic therapy should be carried out in order to determine the magnitude of treatment response and if the goal of treatment is achieved. microalbuminuria. family history of premature CHD**. the use of lipid profile for monitoring of treatment response is RECOMMENDED. Clinical Questions 8 CQ8. For individuals on lipid-lowering therapy. Aside from identifying these populations. **Patients who fulfill the criteria for the diagnosis of familial hypercholesterolemia (see section on screening for familial hypercholesterolemia) should be initiated therapy for aggressive LDL-C lowering It is essential to identify populations at risk and population to whom treatment is recommended. smoker. and left ventricular hypertrophy. hypertension.2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines 33 to at least four weeks. proteinuria. .79 In the 2013 ACC/AHA Guideline for the Management of ST-Elevation Myocardial Infarction. BMI > 25 kg/m2.

In the five studies involving diabetics with ASCVD.000 individuals for the significant beneficial outcomes were 5 for stroke and coronary revascularization. In the trials. screening may not be necessary to commence treatment in this subset of patients. Table 2). 11 for stroke. 27 for stroke and 32 for all-cause mortality. The time to achieve target levels based on the trials ranged from 1 to 8 years. stroke and all-cause mortality. Lipid monitoring in diabetics in primary prevention The use of statins versus placebo was beneficial in the prevention of a critical outcome of fatal and nonfatal MI and four important outcomes. reduction of critical and important outcomes is achieved with use of statins. 10 for fatal and nonfatal MI and 21 for MACE. the use of statins versus placebo was beneficial for four critical outcomes. The NNTs per 1. The NNTs per 1. The role of the lipid profile lies in its ability to determine the percent reduction or the level of LDL achieved after six weeks of treatment to 3-6 months thereafter. similar to patients with ASCVD. namely: stroke. the use of statins versus placebo was beneficial in the prevention of the following critical outcomes. regardless of lipid levels.37 Use of fibrates was not recommended. stroke and cardiovascular death. namely: major cardiovascular events. Since treatment is recommended among patients with ASCVD with or without diabetes. myocardial infarction.34 2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines Lipid determination in secondary prevention In the different clinical trials presented among secondary prevention population (see CQ5). respectively. since regardless of lipid levels and age.000 individuals for the significant beneficial outcomes were 62 for major cardiovascular events. The NNTs per 1. 39 for myocardial infarction.000 individuals for the significant beneficial outcomes were 15 for total mortality. namely: total mortality. acute major CV event (MACE) and coronary revascularization. and 2) to determine the triglyceride level since it is an indirect measure of the adequacy . monitoring of lipid levels should be monitored for two reasons. myocardial infarction.6 mg/dL. lipid profile determination is not necessary for screening but for monitoring therapeutic response since ALL patients should already be on treatment. 22 for MI and 16 for CV death (Section 6. namely: 1) to determine the direction and magnitude of treatment response. The range of diabetic individuals treated for statins was from 45 to 82 years (PROSPER study). However. However. The significant reduction of the outcomes mentioned was achieved after 1 to 5 years of treatment with statins. the treatment commenced with lowest mean baseline total cholesterol and lowest mean baseline LDL-cholesterol were 195 +31 mg/dL and 115 +26.

2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines 35 glycemic control and typically. although wide ranges have been reported). Statins can then be increased to the maximal dose tolerated. so early detection is deemed crucial for the initiation of aggressive lipid-lowering therapy once diagnosis is made. and 11 for coronary . Several guidelines provide the standard diagnostic criteria for patients with FH namely the Dutch Lipid Network Criteria (DLN). 9 for myocardial infarction. 5 for cardiovascular death. stroke. For practical applicability in our setting. the Simon Broome Register (SBR) and the Make Early Diagnosis to Prevent Early Deaths (MEDPED) project.000 individuals for the significant beneficial outcomes were six for all-cause mortality. the lipid profile should be carried out initally as screening (patients with FH have LDL-C levels > 190 mg/dL) then subsequently for monitoring treatment response since ALL patients with FH shoud be on aggressive LDL-C lowering therapy. In the seven different clinical trials included among primary prevention population. 18 for cardiovascular events. Lipid monitoring in patients with Familial Hypercholesterolemia Familial hypercholesterolemia (FH) is an autosomal dominant disorder of a mutation in the low-density lipoprotein receptor (LDL-R) gene resulting in elevated LDL-C levels (typically. The NNTs per 1. cardiovascular death. cardiovascular events and coronary revascularization. the problem with the use of DLN criteria is the limited availability of genetic testing. the DLN criteria (Table 13) should be used since it relies heavily on clinical history and physical exam findings. improvements in the glycemic control can also lead to improvements in the triglyceride level.82 Affected individuals are at increased risk for cardiovascular events and premature coronary artery disease.83 Due to the high cardiovascular risk of these patients. namely all-cause mortality. the use of statins versus placebo was beneficial in the prevention of the following critical outcomes. If the repeat levels are still below the desired reductions or LDL-C level. Lipid determination in primary prevention For individuals without evidence of ASCVD who are ≥ 45 years old and with 2 or more risk factors. a level above 190 mg/dL should raise clinical suspicion. the use of lipid profile for screening is recommended. It has a prevalence of 1 in 500 Caucasians but currenty there are no true estimates of people diagnosed with FH in Asia. myocardial infarction. However.81 To date there is only one study involving Filipinos. 4 for stroke. intensification of lifestyle modification and pharmacologic therapy is warranted.

Apo B.5) 8 LDL-C 250 – 329 mg/dL (6.4) 5 LDL-C 190 – 249 mg/dL (5.36 2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines Table 13. Dutch Lipid Network criteria on the diagnosis of heterozygous familial hypercholesterolemia83 CRITERIA POINTS Family history First-degree relative with known premature* coronary and 1 vascular disease. OR First-degree relative with known LDL-C level above the 95th percentile First-degree relative with tendinous xanthomata and/or arcus 2 cornealis OR Children aged less than 18 years with LDL-C level above the 95th percentile Clinical history Patient with premature* coronary artery disease 2 Patient with premature* cerebral or peripheral vascular disease 1 Physical examination Tendinous xanthomata 6 Arcus cornealis prior to age 45 years 4 Cholesterol levels mg/dl (mmol/liter) LDL-C > 330 mg/dL (>8.9) 1 DNA analysis Functional mutation in the LDLR. low density lipoprotein cholesterol. All the trials included in the analysis used total cholesterol (TC) and/or LDL-C as part of the inclusion criteria. proprotein convertase subtilisin/kexin type 9. with the . familial hypercholesterolemia. apo B or PCSK9 gene 8 Diagnosis (diagnosis is based on the total number of points obtained) Definite Familial Hypercholesterolemia >8 Probable Familial Hypercholesterolemia 6-8 Possible Familial Hypercholesterolemia 3-5 Unlikely Familial Hypercholesterolemia <3 * Premature: < 55 years in men.0–6. PCSK9.4) 3 LDL-C 155 – 189 mg/dL (4. revascularization. low density lipoprotein receptor. < 60 years in women LDL-C. LDLR. apolipoprotein B. FH.0–4.5–8.

should testing reveal elevations in transaminase levels during the course of statin therapy. myopathies. based on the trials. or rhabdomyolysis (Table 14).29 The range of LDL-C in the trials was 108 to 192 mg/ dLwith a mean 155 mg/dL. myopathies and elevations of liver function tests. and the approximate age in which treatment was likewise started was at least 45 years old. Figure 6 outlines a proposed algorithm for the screening and treatment of patients. monitoring of lipid profile after 3 months of treatment is also recommended to determine achievement of treatment goals. To guide clinicians. Monitoring for adverse drug reactions Long-term treatment of dyslipidemia may bring about concerns for adverse drug reactions such as myalgias. the LDL-C levels of Filipinos having acute myocardial infarction was low and a percentage of them were already on statin treatment— this may imply a residual risk. In the trials on primary prevention.84 Serial liver function test monitoring in asymptomatic individuals are not recommended. In patients at risk for development of statin myopathies. Lastly. Lipid profile determination was done after 3 months of treatment and yearly thereafter. determination of lipid profile as a screening tool is necessary to determine baseline levels and to determine who among patients without ASCVD will benefit from statin treatment. Moreover.3 Since the lowest LDL-C level in which treatment was commenced approximated 135 mg/dL. baseline creatine phosphokinase and subsequent monitoring should only be performed when symptoms are present. The average age of patients in the trials was 58 years old (range: 44-71 years). .9 to 5 years) for benefit to be achieved. myositis. Statin-induced Myopathy Statin myopathies are classified as either myalgias. In the ACS registry conducted by the Philippine Heart Association. lipid profile determination is also needed to monitor treatment response. Baseline measurement of hepatic transaminase levels (alanine and aspartate aminotransferase) should be performed before initiation of statin therapy in patients at risk for developing liver injury. However. the average reduction of TC and LDL-C was 20% and 29% respectively with a minimum duration of 1 year (range: 1.2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines 37 lowest TC and LDL-C levels of 168 mg/dL and 94 mg/dL coming from the JUPITER trial. the recommended course of action is outlined in Figure 7.

1 and 0.e.) This risk seems to exist only in those with risk factors for diabetes. lipid profile is used for screening and monitoring of effect of treatment. left ventricular hypertrophy and post menopausal women ** The guideline recommends high intensity dose of statins to reach target ** Treatment goal is to reduce LDL-C by >30%. BMI 25 kg/m2. smoker. family history of premature coronary heart disease. hypertension > 140/90 mmHg. or < 70 mg/dl Note: If the patient is suspected or considered to have Familial Hypercholesterolemia (FH) based on the Dutch Lipid Network score. Finally. around 0. proteinuria. Continuation of statin therapy is recommended Figure 6. .. statins use is associated with a very modest excess risk of new-onset diabetes (i.38 2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines The TRC recommends a localized management algorithm for statin- treated patients with muscle symptoms (Figure 8). respectively. Screening and treatment algorithm for the management of dyslipidemia Legend: * Risk factors: male.3 excess cases per 100 individuals treated for 1 year with moderate-intensity and high-intensity statin therapy.

creatine kinase. FDA. NHLBI. Classification of statin myopathies Myalgia Myopathy Myositis Rhabdomyolysis ACC/AHA Focal or Muscle Severe muscle NHLBI diffuse muscle Any disease of pain damage with aches or muscle with CK damage to weakness with elevation another organ normal CK (i. kidney) and NLA CK > 10 x ULN Myalgia with US FDA CK > 10x ULN CK >50x ULN + organ damage ACC/AHA. ULN. and Blood Institute. CK. Figure 7.e.. AST – aspartate aminotransferase. upper limit of normal. National Heart.2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines 39 Table 14. National Lipid Association. ULN – upper limit of normal . Lung. Food and Drug Administration. American College of Cardiology/American Heart Association. Algorithm for Patients who are on Statins with Elevated Liver Enzymes Legend ALT – alanine aminotransferase. NLA.

should omega-fatty acids be given as an alternative to statin treatment? Statement 9 See Section on Non-statin therapy .40 2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines *If symptoms recur after multiple statin use at multiple dosing. The lowest NNT to achieve benefits from statins is 43 compared with a NNH (harm) of around 250. may use non-statin therapy (fibrates or ezetimibe) Figure 8. Algorithm for Statin-induced Myopathy in these patients due to their increased risk of ASCVD.85 Clinical Question 9 Among patients with ASCVD.

22% of both fenofibrate and placebo arms have prior cardiovascular diseases. In this update.65. 1.1% in the placebo group.90 (0. This is the only outcome reported under the specific subgroup of patients with ASCVD (Table 15). fibrates are NOT RECOMMENDED as an alternative to statins. 0.88 In the 2006 guidelines.6. 1.80 (0. 1. 0. 95% CI) Total Mortality 2 2926 0.76 (0.97]) and cardiovascular events (OR 0.02) Stroke 1 2531 0. CHD death and revascularization. In the LOCAT study.86.79 (0.88]) among 2. In VA-HIT.77 [95% CI 0. a HDL-C of 40 mg/dL or less. Summary of study outcomes for the use of fibrates versus placebo among individuals with ASCVD Outcome Studies Participants Effect Estimate NNT (RR. bezafibrate study was not included because it is not locally available. . the authors reported cardiovascular event rates of 25.89 (0. 1. no mortality was noted during the study for either arm. 1. Summary of Evidence The evidence on fibrates was taken mainly from the Veteran’s Affairs High-density lipoprotein Intervention Trial (VA-HIT) and a subgroup of patients with pre-existing ASCVD in the Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (FIELD) study. the study on bezafibrate was included in the analysis. In the FIELD study. There was no effect on all-cause mortality. 0.80. Among these patients.2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines 41 Table 15.15) death Nonfatal MI 1 2531 0. stroke.08) Fatal CHD/CV 1 4662 0.73 [95% CI 0.61.61.87 The LOCAT study also contributed a small number of patients.08) revascularization Non-statin Therapy Use of Fibrates in non-diabetic individuals with established ASCVD Among patients with established ASCVD.5% in the fenofibrate group and 25.93 (0. gemfibrozil reduced nonfatal myocardial infarction (OR 0.07) Coronary 1 2531 0.55.69.97) 34 CHD death 1 2531 0.531 men with coronary heart disease.76. and an LDL-C level of 140 mg/dL or less.

In the review of literature.86. DAIS (2001). given the very low quality of evidence. Thus.2Hence. which was not one of the outcomes that were included in this guideline. A second downgrade was given for indirectness since the populations included were not statin-intolerant patients. the full data set was also reported. The studies were all done in Caucasian populations and Asians.89-92 In the original guideline published in 2006. only 2 studies were included. since these were purely secondary prevention trials. the quality of the evidence is low with the downgrade due to the question of directness. 48% of the study subjects also had a history of CV disease whose data could not be extracted apart from the main trial results. fibrates are not recommended as an alternative to statin therapy in patients with established ASCVD. Summary of the evidence Evidence on the use of fibrates for primary prevention of cardiovascular outcomes were derived from 4 different clinical trials: the SENDCAP (1998). For FIELD.87. and in particular Filipinos were not included in the samples that were included in these trials. DAIS (2001). there were two other trials on the use of fibrates among diabetic individuals: the BIP (2000) and VA-HIT (2002).42 2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines The GRADE Pro balance sheet (Appendix 2 Table 2. Use of Fibrates on diabetic individuals without established ASCVD For diabetic individuals without evidence of ASCVD. only three trials were included in the analysis: SENDCAP (1998). this statement updates the previous recommendations. HHS study was excluded not only because it had a very small subgroup of patients with diabetes (N= 135. In the end. Data from the primary prevention aspect of the trial could not be separated from the rest of the subjects and hence. representing 3% of the total number of volunteers) but also because it reported a composite outcome of myocardial infarction and CV death. and FIELD (2005). was reported as a combined total of all patients with and without history of CV disease. Two of the four trials (FIELD and DAIS) are combined primary and secondary prevention studies on diabetic individuals. fibrates are NOT RECOMMENDED as an alternative to statin for the primary prevention of cardiovascular events. they were not included in the meta-analysis nor the GRADE PRO review. FIELD (2005) and HHS (1987). 22% of the trial subjects had a history of previous cardiovascular disease. Generally.93 However.For DAIS. .10) shows the quality assessment of the evidence on the use of fibrates in secondary prevention.

stroke or CVD.795 RR 1.1 (0.4%) for the treatment (gemfibrozil) group and 8/76 (10. Until more data are available.0. It was only for the composite outcome of MACE where there was a small.377 1.377 1. 95% CI) Total Mortality 3 10.94 to 1. Summary of Evidence on the use of Fibrates Among Diabetic Individuals.85 (0.377 RR 0. there appears to be no evidence to recommend routinely adding fibrates to statins once LDL-cholesterol goals have been reached.09 (0. None of the trials involved Asians specifically Filipinos. based on the lack of a Filipino population (applicability) and the inclusion of small studies (DAIS and SENDCAP) that contributed to imprecision. Of the six outcomes that were considered (total mortality. It may be considered among men with high baseline TG and low HDL-C once LDL-C has been reached.85 (0. Comparison with other guidelines The recommendations for the use of fibrates in this guideline are similar to other guidelines. CV deaths.98) and NNT of 100. coronary revascularization and major adverse cardiovascular events).09 (0.87 to 1. The outcomes of fatal and non-fatal MI. GRADE PRO evaluation of evidence quality for each outcome (Appendix 2 Table 2. Outcome Studies Participants Effect Estimate NNT (RR. statistically significant result in favor of fibrates with an RR 0.37) NS Stroke 1 9.32.2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines 43 Table 16.9) showed that the quality of evidence for the significant outcome was low.73.73 to 0. as well as coronary revascularization were not investigated by the fibrate trials. in that the principal drug for the primary .5%) for the placebo group for a RR of 0. The pooled data for each of 3 of the single outcomes (total mortality. Thus. only four were investigated as outcomes by the clinical trials on fibrates. for primary prevention in diabetic individuals without ASCVD.4) NS Major Adverse 3 10.26) NS Cardiac mortality 3 10.98) 100 Cardiovascular Events Data from the HHS revealed that the incidence of the combined outcome of MI and cardiac death is 2/59 (3. fibrates are not recommended.86 to 1. fatal and non-fatal MI. CV deaths and Stroke) did not show any statistically significant results in favor of fibrates (Table 16).

19 (0. fibrates and nicotinic acid) may be used to achieve the LDL-C targets.65. and an optional target of < 70 mg/dL for diabetics without previous CV events but who may be high risk for CV outcomes because of established CAD. Fatal and non-fatal MI.371 0. For individuals not at LDL-C target despite statin therapy as described.45) Major 3 8.388 0. this is however. The Canadian Diabetes Association (CDA) recommends the use of statins as first line therapy to achieve an LDL goal of < 2.0 mmol/L.44 2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines Table 17.99) 62 Fatal CHD/CV 2 12.710 0.84. The CDA further states that in patients achieving target LDL-C with statin therapy. 1. and coronary vascularization was not collected separately as an outcome among the clinical trials on fibrates.0 mmol/L (approximately 880 mg/dL) to prevent pancreatitis (in some guidelines even for TG > 500 mg/dl). and strokes or cerebrovascular disease based on moderate quality data. but this was based on low quality evidence. cardiovascular deaths. a combination of statin therapy with second-line agents (which may include bile acid sequestrants. 1. Thus.79. fibrates for primary prevention among diabetic individuals without prior ASCVD is not recommended since no statistically significant effect was found for the critical outcomes of total mortality. Summary of Evidence in the use of PUFA among Individuals with ASCVD Outcome Studies Participants Effect Estimate NNT (RR. .08) death Stroke 3 15. the routine addition of fibrates or niacin for the sole purpose of further reducing cardiovascular risk should not be used (Grade A Level 1A).211 1. The statin dose should be optimized to reach the LDL goal of less than 100 mg/ dL for most diabetic individuals. fibrates may be given among diabetic individuals as primary treatment when the TG > 10.38 Similar to other people.501 0.91 (0.17) Coronary 1 2. It was only for major adverse cardiovascular events (MACE) that is a composite outcome where a small statistically significant effect of fibrates was found. 0. 1. 1.82 (0.87 (0.20) revascularization prevention of cardiovascular outcomes should be statins. a Grade D recommendation based on the consensus of their panel of experts.63.97. cholesterol absorption inhibitors. 95% CI) Total Mortality 4 15.97 (0.

97. 1.70.45]) and revascularization (RR 0. nonfatal MI (0. the IMPROVE-IT.12) shows the quality assessment of the evidence on the use of PUFA in secondary prevention. PUFA is not recommended for the secondary prevention of cardiovascular events. but there was no effect on CV deaths (0.19 [0. and in particular Filipinos were not included in the samples that were included in these trials. fibrates) and a statin may allow for a greater degree of LDL-C reduction and results in achievement of goal attainment for primary and secondary prevention.17].13]). 1. demonstrated that the combination of 40 mg of ezetimibe and 10 mg of simvastatin in patients hospitalized for acute coronary syndrome may be beneficial.65. 1.96. 1. stroke (1.95 Two studies also included patients taking statins but the population from both intervention and placebo groups are comparable and did not significantly affect the heterogeneity and most of the outcomes. In the GISSI HF study. A recently published trial on the use of the combination of ezetimibe plus statin treatment. but data pertaining to this specific population is not available in the study. Thus.82 [0.91 [0.0.99]).63.99 Included . Combination Therapies The TRC and the voting panel are in agreement that combination therapy of a non-statin therapy (eg: omega 3 FA.94.84. Generally. 1. The studies were all done in Caucasian populations and Asians.89 [0.97 Two of the five RCTs are open label studies.2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines 45 Use of Omega-3 Fatty Acid For patients with evidence of ASCVD.20]).87 [0. 50% of heart failure causes are ischemic.94-98 Studies included were randomized controlled trials comparing PUFA of at least 1 g versus placebo for secondary prevention of cardiovascular events. due to the low quality of evidence.79.96 All-cause mortality was decreased by PUFA (RR 0. The GRADE PRO balance sheet (Appendix 2 Table 2. poly-unsaturated fatty acid (PUFA) or omega 3 fatty acid is NOT RECOMMENDED as an alternative to statins for the secondary prevention of cardiovascular events. MACE (0. the quality of the evidence is low with the downgrade due to the question of risk of bias and directness. thus increasing the risk of bias.08]). ezetimibe. Summary of the evidence The evidence was taken from pooled analysis of five studies.97 [0.

The ACCORD Lipid trial showed that there is no evidence to administer fenofibrate to be routinely added to a statin for the treatment of dyslipidemia in patients with type 2 diabetes mellitus. The combination of niacin and statin was investigated in two clinical trials. patients on the combination reached a mean LDL-C of 53. The issue on combining fibrates and statins is answered directly by the ACCORD lipid trial. nonfatal stroke.7% vs 34. unstable angina requiring rehospitalization.016). or death from cardiovascular causes with the mean follow- up was 4. or 50 to 125 mg/dL if not on lipid-lowering therapy. nonfatal myocardial infarction.46 2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines patients had an LDL-C of 50 to 100 mg/dL if on lipid-lowering therapy. p=0.7% risk reduction in the primary endpoint of combined outcome of cardiovascular death.7%. the combination of ezetimibe and simvastatin may provide marginal benefit in post ACS patients. adding fenofibrates to statin may have a possible benefit for patients with both high baseline triglyceride level and a low baseline level of HDL cholesterol. patients on the combination therapy had a 3.7 mg/dL vs 69. Both clinical trials showed no benefit in combination therapy of niacin and statin.100. The pre-specified subgroup analysis showed heterogeneity in the treatment effect according to sex. Lipid-lowering Effect of Non-statin therapies that are Available in the Philippines Non-statin % Change in % Change in % Change in therapy Triglycerides LDL-C HDL-C Fibrates 20%-50% decrease 5%-20% decrease 10%-20% decrease Omega-3 20%-50% decrease 5%-10% increase 1%-23% increase fatty acids Ezetimibe 0-7%% decrease 18% decrease 1%-1% increase . coronary revascularization (≥30 days after randomization). However.101 however. After the 7-year follow- up. NNT was 50. the TRC recommendation is to attempt LDL-C reduction using statin therapy first.001). these were not appraised by the TRC. Based on this new data from the trial.5 mg/dL in those on simvastatin alone (p<0. with a benefit for men and possible harm for women. since the drug is not available in the Philippines. The primary outcome was the first occurrence of nonfatal myocardial infarction. If the patient cannot attain the LDL-C goal Table 18. Furthermore. the AIM-HIGH and HPS2 THRIVE trials.7 years.41 This study randomly assigned 5518 patients with type 2 diabetes who were being treated with open-label simvastatin to receive either masked fenofibrate or placebo. Therefore. or nonfatal stroke (32.

the TRC is in agreement that the value of HDL-C has yet to be answered by clinical trial evidence and there is no recommendation to target a particular level to confer reduction in CV risk.102 The pleiotropic effects of HDL exist independent of HDL-C mass (measured as HDL cholesterol in lipid profile). resulted in a comprehensive set of evidence based clinical recommendations.104 For selected patients with severe hypercholesterolemia. however. Limitations of the Guidelines Several limitations were encountered during the process of creating the 2015 CPG. if left untreated. improved endothelial functions and improved insulin sensitivity. Upcoming treatments such as Proprotein convertase subtilisin kexin 9 inhibitors (PCSK9 inhibitors) and mipomersen are promising therapies that if proven safe. Until such testing becomes available to determine functionality of HDL-C. Future Lipid lowering therapies Patients with severe hypercholesterolemia with LDL-C levels of > 190 mg/dl. The clinical trials analyzed . Thus. HDL lowering therapies The controversy between HDL cholesterol and CVD continues to exist. As seen in the NNHeS data above. antioxidative functions. Filipinos have very low levels of HDL-C and raising the levels may lead to a decrease of ASCVD. clinical trials of high dose niacin. we did not consider data from poor quality RCTs ad observational studies.103. However. as HDL exert several functions in the body such as anti-inflammatory effects. then other locally available therapies may be combined. may make treatment goal for cholesterol levels attainable to these types of patients.2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines 47 recommended by the 2015 Guideline with statin monotherapy either because of an intolerance to the necessary dose of statin.102 These pleiotropic effects might lead to clinically significant improvements in the cardiovascular health of patients. HDL-C may not be the right biomarker to reflect HDL-C function. may have markedly increased risk of ASCVD. Table 18 shows the estimated effect of currently available non-statin therapies on lipid parameters. LDL apheresis may also be considered.102 Thus. The evidence obtained from the trials only involved randomized controlled trials and some meta-analyses. omega-3 fatty acids or Cholesteryl ester transferase protein (CETP) inhibition did not improve CV outcomes despite significantly increasing HDL-C. This approach. Plasma levels of HDL-C is inversely related with the incidence of coronary heart disease.

The presence of generic statin medications in the Philippines has allowed patients to be prescribed with medications with less problems on compliance and adherence to treatment. Fernandez MBD. Stoehr E. Kunz Regina. References: 1. The updated 2015 CPG is designed to be a guide for clinicians in managing dyslipidemia for the Filipino patient. Lopez EA. Trends in presenting characteristics and hospital mortality among patients with ST elevation and non-ST elevation myocardial infarction in the National Registry of Myocardial Infarction from 1990 to 2006. 4.Food and Nutrition Research Institute. Gibson CM. 2008. Am Heart J. compared to the previous one.42. Circulation. thus analysis and grading of evidence were downgraded.org/images/8thNNSResultsNCD. Punzalan FER. Chandra-Strobos N. 2008 National Nutrition and Health Survey Group (NNHS) report. This. Oxman Andrew D. 2007.156(6):102 5. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. Because of this.who. Budoff MJ. Available at: http://www. et al. Burden of selected risk factors to non-communicable diseases (NCDs) among Filipino adults. both for diabetic and non-diabetic patients. 6. Accessed 15 August 2015. Canto JG. most statements are only RECOMMENDED.pdf. Peterson ED. should not replace sound clinical judgment by doctors and the ultimate decision for treatment should involve both clinician and the patient. WHO Country Profiles (Philippines).336:924.pdf. 2008. Nasir K. Phil J Cardiol 2013. Wong NDm et al. BMJ 2008. French WJ.2 year Results. CONCLUSIONS Six clinical statements were made by the TRC and the recommendations revolve around the holistic management of dyslipidemia. We hope in the future that more clinical trials be made with Filipino patients as subjects. Available at: http://philheart. 3. Gore JM. The issue on cost were not included in the present guidelines. Lifestyle modification should be recommended to all patients regardless of their CVD risk. . Caole-Ang IV. 2.48 2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines do not involve Filipino patients. Falck-YtterYngve. Family History of Premature Coronary Heart Disease and Coronary Artery Calcification Multi-Ethnic Study of Atherosclerosis (MESA). The simplified algorithm was provided to serve as a quick reference in the management of clinicians. Reyes EB. Alonso-Coello Pablo. 116: 619-626. High intensity statins are recommended to lower LDL-C by > 30% or < 70 mg/dl in the primary and secondary prevention of ASCVD. Abanilla JM. Philippine Heart Association-Acute Coronary Syndrome Registry. however. Frederick PD. Abola MTB. Taguig: Food and Nutrition Research Institute.int/nmh/ countries/phl_en. Pollack CV Jr. Rogers WJ. Yaneza LO. Vist Gunn E. Guyatt Gordon H. Ornato JP. Steering Committee Members for the Philippine Heart Association-Acute Coronary Syndrome (PHA-ACS) Registry. 2014.

Lipid Modification: cardiovascular risk assessment and the modification of blood lipids for the primary and secondary prevention of cardiovascular disease. Philippine College of Chest Physicians. Food and Agriculture Organization. Cochrane Database Syst Rev. 2002.2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines 49 7. Stamler J. et al. Circulation 1995. Stone. Kuopio Atherosclerosis Prevention Study (KAPS): A Population- Based Primary Preventive Trial of the Effect of LDL Lowering on Atherosclerotic Progression in Carotid and Femoral Arteries. Jamrozik K. 14. 11. Position Statement on Electronic Cigarettes (E-cigarettes) and Electronic Nicotine Delivery Devices. Improving maximum walking distance in early peripheral arterial disease: randomised controlled trial. Dans AL. NJ et al. Anthonisen. 142 (4):233-239. N Engl J Med 2003. Sit JW. J Clin Lipidol 2013. 2012 May 16.stm. Aust J Physiother. 9. Norman P. Wong TK. Reduced or modified dietary fat for preventing cardiovascular disease. Roberts FG. Larsen N. Burden of Malnutrition in a Tertiary Care Hospital in Baguio City. Salonen R. SAGE Open July-Sept 2013:1–7. Intensified multifactorial intervention in patients with type 2 diabetes mellitus and microalbuminuria: the Steno type 2 randomised study. Duante CA. Sy RG.5:CD002137. 8. 16. Wing RR.353:617 –622 20. Parving H-H. NEJM 1995. Preventive Medicine 1985. N Engl J Med. Nutrition country profiles (Philippines). Abelardo NS. Journal of the American Heart Association.369(2):145-54. 279(20): 1615-1622. Downs JR. Lancet 1999. Summerbell CD. 23. 12. Hooper L. JAMA 1998 May 27. et al. 26. August 2012: 1. Sills D. Allen Y. Multiple Risk Factor Intervention Trial Revisited: A New Perspective Based on Nonfatal and Fatal Composite Endpoints. Pedersen O. Look AHEAD Research Group. et al. 10. 15.5 Year Mortality: A Randomized Controlled Trial. Vedel P. 17. 21. 2013 Jul 11.org/ag/AGN/nutrition/PHL_en.92:1758-64. Prevention of coronary and stroke events with atorvastatin in . An International Atherosclerosis Society Position Paper: Global recommendations for the management of dyslipidemia. Vedel P. Punzalan FE. Primary Prevention of Acute Coronary Events With Lovastatin in Men and Women With Average Cholesterol Levels Results of AFCAPS/TexCAPS. Gæde P. for the West of Scotland Coronary Prevention Study group. A nurse-led cardiac rehabilitation programme improves health behaviours and cardiac physiological risk parameters: evidence from Chengdu.7: 561-565. J Clin Nurs. Paz-Pacheco E. 18.348:383–393. 25.. Sever PS. Brancati FL. Shepherd J. 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults. The Oslo Study: Diet and Antismoking Device. Jiang X. During the Trial. 2005. Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. Holme I.48(4):269-75. 19.16:3-6. Available at: http://www. Parving HH. 13. Accessed 15 August 2015. Dominguez JR. Thompson R. 2007 Oct. et al. Morales DD. Jensen GVH. China. Fowler B. Moore HJ. Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. Nicholas et al in behalf of the Lung Health Study Research Group. Coronary and Cardiovascular. 2012. 1-7. 14: 279-292. et al. Circulation. Philipp J Chest Dis 2015. for the AFCAPS/TexCAPS Research Group. Grundy SM on behalf of the Expert Dyslipidemia Panel. Wilkinson E.33:1301-7. 24.. Prevalence of atherosclerosis-related risk factors and diseases in the Philippines.22(5):440-7. et al. et al. Bolin P. National Institute for Health and Care Excellence of the United Kingdom 2014. The effects of a Smoking Intervention on 14. J Epidemiol. JAMA February 14. Davey Smith G.fao.16(10):1886-97. 22. Pedersen O. Gæde P.

. Yusuf S. Ridker PM. 39. 28. J. . 31.361:2005-2016. Eur Heart J. Jimeno CA. The Lancet 2003 Apr 5. for the JUPITER Study Group. Can J Diabetes.359(21):2195-2207 30. Nakamura H. NEJM 2008. Santiago D.364(9438):937-952. Heart Protection Study Collaborative Group. on behalf of the CARDS investigators. Lancet June 14.364:685-696. 27. Primary prevention of cardiovascular disease with pravastatin in Japan (MEGA Study): a prospective randomised controlled trial.288 (23): 2998-3007. 2011 Jul. 47: 99-105. ESC Committee for Practice Guidelines (CPG) 2008-2010 and 2010-2012 Committees. Lancet August 21.37Suppl 1:S110-6.110:2809-16. A Prospective Study of Pravastatin in the Elderly at Risk (PROSPER). Hegele RA.360:685-696. Lancet September 30. Lantion-Ang FL. 29. JAMA December 18. Dyslipidemia.32(14):1769-818. in the Anglo-Scandinavian Cardiac Outcomes Trial—Lipid Lowering Arm (ASCOT-LLA): a multicenter randomised controlled trial. 38. Lancet 2002. Complications and cardiovascular risk factors among newly-diagnosed type 2 diabetics in Manila. The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Hypertensive Patients Randomized to Pravastatin vs Usual CareThe Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT). 36. Primary prevention of cardiovascular disease with pravastatin in Japan (MEGA Study): a prospective randomised controlled trial. for the MEGA Study Group. for the MEGA Study Group. American Diabetes Association. 2013. 29(7):1478–1485. Reiner Z. 2002. Nakamura H. for the Prevention of Renal and Vascular Endstage Disease Intervention Trial (PREVEND IT) Investigators.368:1155–63. et al. 2013 Apr. European Association for Cardiovascular Prevention & Rehabilitation. Rosuvastatin to Prevent Vascular Events in Men and Women with Elevated C-Reactive Protein. Catapano AL. Shepherd J. 2004. Knopp RH. ESC/EAS Guidelines for the management of dyslipidaemias: the Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS).368:1155–63. 33. Lancet September 30. Diabetes Care. 2006. Mancini GB. Standards of medical care in diabetes—2013. for the PROSPER Study Group. Phil. Leiter LA. Circulation 2004. Efficacy and Safety of Atorvastatin in the Prevention of Cardiovascular End Points in Subjects With Type 2 Diabetes: The Atorvastatin Study for Prevention of Coronary Heart Disease Endpoints in Non-Insulin-Dependent Diabetes Mellitus (ASPEN).36(suppl 1):S11-S66. Sy H. Colhoun HM. Arroyo M. et al. Diabetes Care July 2006. et al. et al. 37. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Major Outcomes in Moderately Hypercholesterolemic. et al. on behalf of the ASPEN Study Group. Internal Medicine. 2003. MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomised placebo controlled trial. et al.. et al. See J. Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. 2009.361(9364):1149-58. et al. Fojas MC. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicenter randomised placebo-controlled trial. Effects of Fosinopril and Pravastatin on Cardiovascular Events in Subjects With Microalbuminuria.50 2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines hypertensive patients who have average or lower-than-average cholesterol concentrations.. Laurel A. 35. 32. Lancet 2004. 2006. 40. 34. et al. Asselbergs FW.

Teo KK. Shukla A. 2002. Tandon N. Peto R et al. Bogousslavsky J. Rutherford JD. Ellis SG. Atorvastatin improves left ventricular systolic function and serum markers of inflammation in nonischemic heart failure. Italian Heart Journal. The effect of fluvastatin on cardiac events in patients with symptomatic coronary artery disease during one year of treatment. Sleight P. New England Journal of Medicine. High.362:1563-74. European Heart Journal. Lerakis S. Treatment with atorvastatin to the National Cholesterol Educational Program goal vs ‘usual’ care in secondary coronary heart disease prevention. Mir MQS. N Engl J Med 2010. Ludwig M. Espeland MA. Jain A. 2005. 144(1):263-270. Fluvastatin treatment after first PCI. 45. 46. 2000. The GREek Atorvastatin and Coronary-heart-disease Evaluation (GREACE) study. American Journal of Cardiology. Clinical outcomes in managed-care patients with coronary heart disease treated aggressively in lipid-lowering disease management clinics: the alliance study. Koren MJ. Cholesterol and Recurrent Events Trial investigators. Sola S. Schwandt P. Armitage J. Atherosclerosis. Sharma MK. Randomized trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Mancini GB. 50. 47(2):332-337. 2003. Symeonidis AN. 344(8934):1383- 1389. Long-term . Buller CE. 47. Parish S. Prevention of atherosclerosis progression using atorvastatin in normolipidemic coronary artery disease patients . 55. 76(9):54C-59C. 1995.dose atorvastatin after stroke or transient ischemic attack.A controlled randomized trial. Current Medical Research & Opinion. Journal of the American College of Cardiology. 18(4):220-228. MRC/BHF Heart Protection Study of cholesterol-lowering therapy and of antioxidant vitamin supplementation in a wide range of patients at increased risk of coronary heart disease death: Early safety and efficacy experience. New England Journal of Medicine. Riegger G. 51. New England Journal of Medicine. PLAC I investigation. Rosman HS. Cole TG et al. Goldstein LB. 339(19):1349-1357. 1999. Crouse Iii JR. Lancet. III. Journal of the American College of Cardiology. 52. The ACCORD Study Group. 42. Lemos PA. Burton JR. Catellier D. 1999.2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines 51 41. 44. Widimsky J. 44(9):1772-1779. 56. Park JS. Pitt B. Effects of Combination Lipid Therapy in Type 2 Diabetes Mellitus. Papageorgiou AA. McGovern ME. Meade T. 49. Mercouris BR. 2006. 1995. 1998. Plante S. Hunninghake DB. Byington RP. 54. Pravastatin. 335(14):1001-1009. 1994.II). Bond MG. Collins R. Athyros VG. 2004. Basayannis EO et al. Sacks FM. 48. Rudolph AE et al. Amarenco P. lipids. 1996. 53. 26(5):1133-1139. Pfeffer MA. 20(9):12. 43. Weidinger G et al. Moye LA. Tymchak W et al. The Long- Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. Results of the low-dose (20 mg) pravastatin GISSI Prevenzione trial in 4271 patients with recent myocardial infarction: do stopped trials contribute to overall knowledge? GISSI Prevenzione Investigators (Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico). Furberg CD. Rouleau JL. Abletshauser C. 1(12):810-820. Khan BV. Goel PK. Callahan A. Pravastatin limitation of atherosclerosis in the coronary arteries (PLAC I): reduction in atherosclerosis progression and clinical events. Athyrou VV. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cardiology Review. and atherosclerosis in the carotid arteries (PLAC.15. Serruys PW. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. Indian Heart Journal. 355(6):549-559. 2006. 57(6):675-680. Journal of the American College of Cardiology. Hennerici M. 20(10):725-741.

Yamada T. 59. Faergeman O. High-dose atorvastatin vs usual-dose simvastatin for secondary prevention after myocardial infarction: the IDEAL study: a randomized controlled trial. Morita T. Sleigh P. Am Heart J.064 survivors of myocardial infarction: a double-blind randomised trial. Kawaguchi A. 67. Kastelein JJ. JAMA. White HD et al. 61. Armitage J. Sacks FM. Grundy SM. Moye ́ LA. (2003) Secondary prevention of cardiovascular events with long-term pravastatin in patients with diabetes or impaired fasting glucose: results from the LIPID trial. Bowman L. Circulation. 66. Kirby A. et al. Simes LA. Parish S. Fox KA. Wu CC. LaRosa JC. Tanphaichitr V. 101: 478-487. Can J Cardiol. 376(9753):1658-1669. 102(15):1748-1754. 352(14):1425-1435. Blazing MA. New England Journal of Medicine. et al. (1997) Cholesterol lowering with simvastatin improves prognosis of diabetic patients with coronary heart disease. Haynes R et al. Collins R. 294(19):2437-2445. Circulation 98: 2513–2519. 2001. Gregory G. et al. Colquhoun D. Armitage J. Goldberg RB. Lee YT. Three-year follow-up results of angiographic intervention trial using an HMG-CoA reductase inhibitor to evaluate retardation of obstructive multiple atheroma (ATHEROMA) study. Tan ATT. Pedersen TR. 2004;148(1). Effect of Pravastatin Compared With Placebo Initiated Within 24 Hours of Onset of Acute Myocardial Infarction or Unstable Angina: The Pravastatin in Acute Coronary Treatment (PACT) Trial. Lancet. Keech A. Nobuyoshi M. Barter P. 70. de Lemos JA. Kioka H. Intensive lowering of LDL cholesterol with 80 mg versus 20 mg simvastatin daily in 12. Bulbulia R. Suyono S. Pyra ̈la ̈ K. Holme I et al. Anderson TJ. Diabetes Care 26: 2713–2721. Lancet 361: 2005–2016. 62. JAMA. Yamamoto A. Wallendszus K. 2004. The Care Investigators. Comparing the efficacy and safety of Atorvastatin and Simvastatin in Asians with elevated low density lipoprotein cholesterol – A multinational multicenter double blind study.52 2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines effects of cholesterol lowering and angiotensin-converting enzyme inhibition on coronary atherosclerosis: The Simvastatin/Enalapril Coronary Atherosclerosis Trial (SCAT).29(2):151-67. 2000. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. Wiviott SD. Thompson PL. et al. 60. 153(6):1055. Pedersen TR. Schwartz. 2005. 64. Tsukamoto Y et al. PhD.285:1711-1718. Howard BV. Olsson AG. et al. Best J. JAMA. Mellies MJ. 292(11):1307-1316. 2005. 2005. 63. 68. MD. 58. American Heart Journal. Yokoi H. Circulation Journal. Faergeman O. 2013 Feb. Waters DD. Kjekshus J. Lewis EF. 2010. Sy RG. Olsson AG. Long-term effect of atorvastatin on neurohumoral activation and cardiac function in patients with chronic heart failure: A prospective randomized controlled study. Peto R (2003) MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial. Diabetes Care 20: 614–620. 69(8):875-883. Mitsudo K. Node K. Mine T. Tikkanen MJ. Early intensive vs a delayed conservative simvastatin strategy in patients with acute coronary syndromes: phase Z of the A to Z trial. Effects of Atorvastatin on Early Recurrent Ischemic Events in Acute Coronary Syndromes The MIRACL Study: A Randomized Controlled Trial. Shear C. 2007. J Formos Med Assoc 2002. (1998) Cardiovascular events and their reduction with pravastatin in diabetic and glucose- intolerant myocardial infarction survivors with average cholesterol levels: subgroup analyses in the cholesterol and recurrent events (CARE) trial. . 65. 2012 update of the Canadian Cardiovascular Society guidelines for the diagnosis and treatment of dyslipidemia for the prevention of cardiovascular disease in the adult. Rahimi K. A subgroup analysis of the Scandinavian Simvastatin Survival Study (4S). Fruchart JC et al. 69. 57.

Circulation. Allan GM. Statin-induced diabetes: too sweet a deal? Can Fam Physician. 86.100(Suppl 1):I–303. placebo- controlled trial (the FACS-trial). Rubins HB. et al. Humphries SE. NEJM 1999.59(7):e311. 73. The FIELD study investigators. Amsterdam EA. et al. Livy A.110(9):1061-8. 83. 82. 2010 May 25. Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: consensus statement of the European Atherosclerosis Society. 2014 PHA Clinical Practice Guidelines for Diagnosis and Management of coronary artery disease. Sato H.350:1495-504. Ascheim DD.1(1): 22-31. 1997.366:1849–61. Int J Clin Pract. 75. 84. Shimada K. Alan D. et al. 2013. J Am Coll Cardiol. Kurata T. O’Gara PT. Sy RG. Den Hartog FR. Okazaki S. et al.61(4):e78-140. et al. 2004 Aug 31. Wenger NK. Kultursay H.34:3478-3490a. Evrengul H. JAMA.64(24):e139-228. 2002. Cannon CP. 74. Blanckaert N. OMICS Res 2011. Kesteloot H. double-blind. Macaya C. Acta Cardiol. 2014 Dec 23.11:61. Lesaffre E. J Atherosclerosis Thrombosis 2005. Low-Density Lipoprotein Receptor (LDL-R) Gene Mutations Among Filipinos with Familial Hypercholesterolemia. 2014 AHA/ACC Guideline for the Management of Patients with Non-ST-Elevation Acute Coronary Syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Yokoyama T.Early statin treatment in patients with acute coronary syndrome: demonstration of the beneficial effect on atherosclerotic lesions by serial volumetric intravascular ultrasound analysis during half a year after coronary event: the ESTABLISH Study. .287:3215–22. et al. Society for Cardiovascular Angiography and Interventions.341:410-8. Intensive versus Moderate Lipid Lowering with Statins after Acute Coronary Syndromes. Fluvastatin in the first-line therapy of acute coronary syndrome: results of the multicenter. Schaafsma HJ. N Engl J Med 2004. Eur Heart J. J Am Coll Cardiol.Trials. Van Kalmthout PM. Can L. Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group. Fye CL. 81. Circulation.12(5):276-283. Effects on long-term fenofibrate therapy on cardiovascular events in 9795 in the people with type 2 diabetes mellitus (the FIELD study): randomized controlled trial.Gemfibrozil for the secondary prevention of coronary heart disease in men with low levelsof high- density lipoprotein cholesterol. Lancet 2005. Time course of serum lipids and apolipoproteins after acute myocardial infarction: modification by pravastatin. 2014. 78. Fluvastatin for prevention of cardiac events following successful first percutaneous coronary intervention: a randomized controlled trial. Anderson JW. Approach to the Patient Who Is Intolerant of Statin Therapy. Collins D. American College of Emergency Physicians. Nordestgaard BG. Lye SH. 72. Robins SJ. Familial Hypercholesterolemia in Asia: A Review. 76. The short term results of combined use of pravastatin with thrombolytic therapy in acute myocardial infarction. 85. 79. Brindis RG. Kushner FG. Elam MB. 77. et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Daida H. Turkoglu C. 2001. Punzalan FE. Van Loenhout TT. Miyauchi K. Verheugt FW. randomized. 1999. Kayikcioglu M. et al. OstadalP. Rila H.55(5):300-4. 87. Vejvoda J. de Feyter P. Claeys G. Chapman MJ. Turgeon R. Santos RS. Eckel R. Pravastatin in acute ischaemic syndromes: results of a randomised placebo-controlled trial. 2013 Jan 29. 2013 Jul. J Clin Endocrinol Metab 2010.2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines 53 71.52(2):107-16. 80.95(5):2015–2022. Pasig: Philippine Heart Association. Serruys PW. (Abst 1586).

89. 317(20): 1237–45.372(25):2387-97. IMPROVE-IT Investigators. N Engl J Med.341:c6273. Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes. Mänttäri M. Management of hypercholesterolemia for prevention of atherosclerotic cardiovascular disease: focus on the potential role of recombinant anti-PCSK9 monoclonal antibodies. N Engl J Med 1987. Calò L. et al. De Geest B.102:21–7. Verma DR. Mary’s. Lancet 2001. 7 (3 Suppl): S16-S10. Lancet 2008. Circulation 2000. S et al. N Engl J Med 2014. Manninen V. 93. BMJ 2010. double-blind. 103. The Effect of Dietary ω-3 Fatty Acids on Coronary Atherosclerosis: A Randomized.21(4):641–8. Bianconi L. P. Galan. Curr Mol Med. a randomized study. Kesse-Guyot. Cannon CP. Effect of fenofibrate on progression of coronary artery disease in type 2 diabetes: the Diabetes Atherosclerosis Intervention Study. 102. Czernichow. The HPS2-THRIVE Collaborative Group. Diamond JR. Kothny W. Emerging LDL Therapies: mipomersen antisense oligonucleotide therapy in the management of hypercholesterolemia. placebo- controlled trial. changes in risk factors. Elkeles RS. Niacin in Patients with Low HDL Cholesterol Levels Receiving Intensive Statin Therapy. 14 (4): 481-503. et al. Gordts SC.372:1223-30. Koskinen P. Toth LL. Ealing. JACC 2005. et al. Effect of n-3 polyunsaturated fatty acids in patients with chronic heart failure (the GISSI-HF trial): a randomised. Cardiovascular outcomes in type 2 diabetes. Northwick Park Diabetes Cardiovascular Disease Prevention (SENDCAP) Study. 
 104. Helsinki Heart Study: primary prevention trial with gemfibrozil in middle-aged men with dyslipidemia Safety of treatment.15(7):820–5.130(7):554-562. Brinton EA. 371:203-212. 94. A double-blind placebo-controlled study of bezafibrate: the St. J. Diabetes Atherosclerosis Intervention Study (DAIS) investigators. Coronary heart disease incidence in NIDDM patients in the Helsinki Heart Study. et al. 2014 May. Poulter C. Colivicchi F.45(10):1723-8. 91.54 2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines 88.15:86–101. von Schacky C. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Prevention of the angiographic progression of coronary and vein- graft atherosclerosis by gemfibrozil after coronary bypass surgery in men with low levels of HDL cholesterol. Effects of Extended-Release Niacin with Laropiprant in High-Risk Patients. Haapa K. Frick MH. et al. The BIP Study Group. E. 92. 90. The AIM-HIGH Investigators. Elo O. 99. . Muthuramu I. Diabetes Care 1992. Placebo-Controlled Trial. Giugliano RP. Controlled Trial. Circulation 1997. Double-Blind. Diabetes Care 1998. 96. et al.96:2137-43. 2014. Annals of Internal Medicine 1999. 101. 98. Lopid Coronary Angiography Trial (LOCAT) Study Group. A Randomized. Frick MH. 365:2255-2267. Effects of B vitamins and omega 3 fatty acids on cardiovascular diseases: a randomised placebo controlled trial. Secondary prevention by raising HDL-C cholesterol and reducing triglycerides in patients with coronary artery disease – the Bezafibrate Infarction Prevention (BIP) study. 2015 Jun 18. and incidence of coronary heart disease. GISSI-HF investigators. Blazing MA. GISSI PREVENZIONE Investigators. 97.357:905–10. Lancet 1999. N-3 Fatty Acids for the Prevention of Atrial Fibrillation After Coronary Artery Bypass Surgery. Singh N. 95. Pleiotropic effects of HDL: towards new therapeutic areas of HDL-targeted interventions. Angerer P. Rev Cardiovasc Med. of Clin. Lipidology 2013.354:447–55. N Engl J Med 2011. 100. et al.

2007 controlled trial obese people diet vs modified metabolic risk. total controlled trial men with mild modified fat vs mortalit hypercholesterolemia usual diet
 Black 1994 Randomized 133 people with non. their first MI dietary advice
 CV deaths. CV mortality. total MI. total men and women aged and non-fatal 30-50 MI. total and HDL cholesterol beFIT 1997 Randomized 409 women and Reduced and Lipids. serum dysplasia diet cholesterol. Reduced fat Incidence of controlled trial melanoma skin cancer intake vs usual actinic keratosis diet and non- melanoma skin cancer. diet vs usual cardiovascular non-obese Caucasian diet
 mortality. stroke. LDL and HDL cholesterol Azadbakht Randomized 100 overweight and Reduced fat Weight. CV mortality . weight. controlled trial recently recovered from intake vs. total MI BDIT Pilot Randomized 295 women with Reduced fat Dietary Studies 1996 controlled trial mammographic intake vs usual fat. 1990 controlled trial hypercholesterolaemic. cancer deaths Ball 1965 Randomized 252 men who have Reduced fat Reinfarction. stroke. total mortality.1 Characteristics of included studies/substudies on diet modification Study/Year Methods Participants Interventions Outcomes Anderson Randomized 107 moderately Reduced fat Total mortality. total mortality.2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines 55 Appendix 1. death. non-fatal MI. fat diet total mortality. BMI. MACE. total. Included Studies Table 1. cancer diagnoses.

total MI. cancer deaths and diagnoses CARMEN MS Randomized 23 people with at Reduced fat vs Weight. stroke. heart failure. usual diet CV mortality. controlled trial cholesterol >6. body sub-study controlled trial least 3 risk factors for usual diet composition. 
 total mortality. 2001 controlled trial with stage I or II breast usual diet total mortality. total mortality. body 2000 controlled trial people. cancer deaths. 2002 metabolic syndrome lipids. lipids
. total controlled trial hyperlipidaemia and usual diet mortality high risk of CVD .56 2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines Study/Year Methods Participants Interventions Outcomes Boyd 1988 Randomized 21 women with severe Reduced fat vs Mastopathy controlled trial cyclical mastopathy for usual diet symptoms. non-fatal MI DO IT 2006 Randomized 249 patients with Reduced fat vs CVD. cancer deaths and diagnoses. total years and non-fatal MI. controlled trial from an MI modified fat vs reinfarction. cancer deaths DART 1989 Randomized 2033 men recovering Reduced and Mortality. PVD Curzio 1989 Randomized 135 hypertensives with Unclear Blood pressure. total mortality. CV mortality. stroke. cancer deaths CARMEN Randomized 290 healthy overweight Reduced fat vs Weight. CV mortality. non-fatal MI. lipids
. cancer over the past 2 CV deaths. CV mortality. MACE. at least 5 years plasma hormone and lipids. CV deaths BRIDGES Randomized 106 women diagnosed Reduced fat vs Diet and BMI
.5mmol/L weight. total mortality. BMI 26-34 usual diet composition.

CV mortality. CV mortality. least 8% of body weight weight. stroke. total and non- fatal MI Due Low vs Randomized 100 young overweight Reduced CVD risk. 2008 controlled trial adults who had lost at usual diet diabetes risk. total mortality. total mortality. total and non- fatal MI Due Mod fat Randomized 77 young overweight Modified fat vs CVD risk. stroke. total taking ursodeoxycholic mortality acid Houtsmuller Randomized 102 adults with newly Modified fat vs Progression 1979 controlled trial diagnosed diabetes usual diet
 of diabetic retinopathy. total mortality. total MI. cancer deaths and diagnoses. total MI. total and non- fatal MI Dullaart 1992 Randomized 38 Type I diabetics Modified fat vs Albuminuria controlled trial with elevated urinary usual fat and serum albumin lipoproteins. non-fatal MI. 2008 controlled trial adults who had lost at usual diet
 diabetes risk. total MI. stroke. least 8% of body weight modified fat weight. stroke. total MI and angina . least 8% of body weight weight. CV mortality.2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines 57 Study/Year Methods Participants Interventions Outcomes Due Low fat Randomized 73 young overweight Reduced fat vs CVD risk. cancer deaths and diagnoses. total mortality. CV mortality. cancer deaths Frenkiel 1986 Randomized 36 people with Modified fat vs Bile acid controlled trial radiolucent gallstones average diet kinetics. Mod 2008 controlled trial adults who had lost at fat intake vs diabetes risk. cancer deaths and diagnoses.

CV mortality. total and non- fatal MI. testosterone CV mortality. lipids. cancer deaths Ley 2004 Randomized 176 people with Reduced fat vs Lipids. CV balanced diet mortality. CV mortality. ventricular overload . total nutritionally mortality. ventricular fibrillation. cancer diagnoses. intolerance or high total mortality. controlled trial insulin-resistant women vs Modified fat lipids. non-fatal and total MI. stroke. stroke. glucose. non fatal MI. total mortality. cancer deaths and diagnoses McKeown. women with above usual diet
 wellbeing. diet to achieve cancer deaths fat goals
 MeDiet 2002 Randomized 112 healthy Reduced and Breast cancer. Randomized 201 people after 4-monthly Recurrence Eyssen 1994 controlled trial adenomatous colorectal counseling to of neoplastic polypectomy encourage a polyps. vs monthly cancer counseling on diagnoses. cancer deaths McAuley 2005 Randomized 62 overweight and Reduced fat Weight loss. controlled trial postmenopausal modified fat vs weight. stroke. median serum total mortality. normal blood glucose CV death. controlled trial BMI >25 usual diet
 CV risk factors. total diet
 mortality.58 2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines Study/Year Methods Participants Interventions Outcomes Lean 1997 Randomized 110 healthy women. stroke. controlled trial impaired glucose usual diet
 blood pressure. total MI. Reduced fat vs Weight loss. cardiovascular deaths.

total Coron men controlled trial men living in a mental diet vs. anti-oxidative capacity. stroke. total Coron women controlled trial women living in a diet vs.664 institutionalised Modified fat MI. stroke. usual mortality. MI. total mortality. CV mortality. one CVD risk factor cancer diagnoses (no events). total MI
 Moy 2001 Randomized 267 middle-aged Reduced fat Dietary intake. controlled trial siblings of people with intake vs. total MI
 Minnesota Randomized 4.2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines 59 Study/Year Methods Participants Interventions Outcomes Minnesota Randomized 4. total mortality. stroke. cancer deaths. total mortality . cancer diagnoses and deaths NDHS Randomized 224 men living in a Modified fat vs Lipid levels Faribault 1968 controlled trial mental health institute usual diet
 and dietary assessment.393 institutionalised Modified fat MI. 1989 mental hospital diet
 sudden deaths. stroke. CV mortality. usual total mortality. vitamin controlled trial aged 20-55 usual diet and fatty acid intake. cancer deaths. 1989 hospital diet
 sudden deaths. cancer deaths. usual mortality. with at least diet
 CV mortality. total and non- fatal MI MRC 1968 Randomized 395 men who have Modified fat vs MI or sudden controlled trial survived a first MI usual diet
 death. total and non-fatal MI
 MSFAT 1997 Randomized 240 healthy people Reduced fat vs Weight. CV mortality. early CHD. CV mortality.

stroke. CV mortality. CV mortality. total or non-fatal MI. usual assessment. total mortality. cancer diagnoses and deaths . cancer diagnoses. peripheral vascular events NDHS Open Randomized 782 men Modified fat Lipid levels 1st mod 1968 controlled trial diet vs.60 2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines Study/Year Methods Participants Interventions Outcomes NDHS Open Randomized 436 men Reduced and Lipid levels 1st L&M 1968 controlled trial modified fat and dietary diet vs. peripheral vascular events Nutrition & Randomized 122 pre-menopausal Reduced fat vs Body weight. diet total mortality. total and non-fatal MI
 NDHS Open Randomized 431 men Modified fat vs Lipid levels 2nd Mod 1968 controlled trial usual diet
 and dietary assessment. total and non-fatal MI
 NDHS Open Randomized 489 men Reduced and Lipid levels 2nd L&M 1968 controlled trial modified fat vs and dietary usual diet
 assessment
. total or non-fatal MI. CV mortality. non-fatal and total MI. cancer diagnoses. CV mortality. CV mortality. usual and dietary diet assessment
. Breast Health controlled trial women at increased usual diet dietary risk of breast cancer compliance
. total mortality.

cancer diagnoses and deaths Oslo Diet. diabetes. cancer diagnoses. stroke. 2003 controlled trial optimal BP or stage 1 usual diet
 total mortality. non- fatal and total MI. total and non-fatal MI
 Rivellese 1994 Randomized 63 adults with primary Reduced fat Metabolic controlled trial hyperlipoproteinaemia vs Modified fat effects. total mortality. total mortality. 1996 polyp of the large bowel prostate cancer.2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines 61 Study/Year Methods Participants Interventions Outcomes Ole Study Randomized 30 moderately obese Reduced fat vs Body weight. glucose. CV mortality. total and non-fatal MI . non-fatal and total MI. 2002 controlled trial healthy men usual diet
 body fat. Retinopathy controlled trial non-insulin dependant and modified total mortality 1978 diabetics dietary fat vs average diet
 Polyp Randomized 2079 people with at Low fat vs Recurrence Prevention controlled trial least one adenomatous usual diet of polyps. cancer deaths. stroke. Randomized 412 men with previous Modified fat Coronary Heart 1966 controlled trial MI diet vs control
 heart disease morbidity and mortality. insulin
. stroke. hypertension cardiovascular mortality. cancer diagnoses PREMIER Randomized 537 adults with above Reduced fat vs Blood pressure. CV mortality. stroke
 Oxford Randomized 498 newly diagnosed Reduced Retinopathy. total diet mortality. removed total mortality. lipids.

Reduced and Lipids and & Mod 1995 controlled trial 60 with serum total modified fat vs blood pressure
. stroke. non- fatal MI. angina. cholesterol levels 6. Reduced fat vs Lipids and Fat 1995 controlled trial 60 with serum total usual diet blood pressure
. controlled trial risk of breast cancer usual diet
 cancer diagnosis . CV diet mortality. cholesterol levels total mortality 6.62 2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines Study/Year Methods Participants Interventions Outcomes Rose 1965 Randomized 53 men with angina or Modified fat vs. cholesterol levels total mortality 6. CV diet mortality.0mmol/L Seppelt 1996 Randomized 70 women with BMI Reduced fat vs Weight. cancer deaths and cancer diagnoses
 Sarkkinen Fat Randomized 78 people aged 30. cholesterol levels usual diet total mortality 6.5-8.0mmol/L Sarkkinen Red Randomized 78 people aged 30. Reduced fat vs Lipids and vs Mod 1995 controlled trial 60 with serum total modified fat blood pressure
. CV mortality. cardiovascular deaths. total mortality 8. total controlled trial 24-29 usual diet mortality. controlled trial following MI usual diet
 total mortality. cancer deaths Simon 1997 Randomized 194 women with a high Reduced fat vs Total mortality.5-8. total protein 2009 controlled trial obese adults vs Modified fat mortality.5-8. total protein 2009 controlled trial obese adults vs Modified fat mortality.0 mmol/L Sarkkinen Red Randomized 78 people aged 30. Modified fat vs Lipids and Mod 1995 controlled trial 60 with serum total usual diet
 blood pressure
.5. CV mortality. stroke Sacks high Randomized 403 overweight or Reduced fat Weight. total and non-fatal MI. Cardiac events.0mmol/L Sarkkinen Red Randomized 81 people aged 30. cancer deaths and cancer diagnoses
 Sacks low Randomized 408 overweight or Reduced fat Weight.

total and non-fatal MI Veterans Randomized 844 men living at the Modified fat vs. non-fatal MI. stroke. total mortality THIS DIET Randomized 101 people following a Low fat vs Mortality and 2008 controlled trial first MI modified fat morbidity
. Centre (USA) CV mortality.112 women with Reduced fat Total mortality. total MI STARS 1992 Randomized 60 men with Reduced and Angiography
. stroke. CV mortality. diet
 CV mortality. cancer diagnoses and deaths. total MI WHEL 2007 Randomized 3. CV mortality . controlled trial previously treated early intake vs usual invasive breast breast cancer diet
 cancer. angiography diet vs usual CV mortality. CV mortality. cancer deaths. diet
 cancer deaths. controlled trial angina referred for modified fat total mortality. cancer deaths. Total mortality. Admin 1969 controlled trial Veterans Administration usual diet heart disease. total MI
 Strychar 2009 Randomized 32 people with well Reduced fat Triglycerides controlled trial controlled type I vs Modified fat and other CVD diabetes mellitus diet risk factors. Randomized 458 men with previous Modified fat Cardiovascular Heart 1978 controlled trial MI diet vs usual mortality and diet
 morbidity. usual total mortality.2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines 63 Study/Year Methods Participants Interventions Outcomes Sondergaard Randomized 131 people with IHD Reduced and Endothelial 2003 controlled trial plus total cholesterol at modified fat function
. stroke. cancer diagnoses. stroke. least 5mmol/L intake vs. cancer deaths and diagnoses Sydney Diet. total mortality.

437 women with Reduced fat Dietary fat controlled trial localised re-sected intake vs. stroke. cancer diagnoses . cancer diagnoses. baseline cardiovascular events.277 post-menopausal Reduced fat vs. diabetes.835 post. total breast cancer diet
 cholesterol. diabetes. CVD at baseline other cancers. cancer deaths. CV mortality. 2006 controlled trial women aged 50-79 with usual diet total mortality. Breast cancer. cancer deaths. total mortality. stroke. Reduced fat vs. CV mortality. CVD 2006 controlled trial menopausal women usual diet total mortality. usual intake. cancer diagnoses.64 2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines Study/Year Methods Participants Interventions Outcomes WHI with CVD Randomized 2. weight and waist. Breast cancer. cardiovascular events. non-fatal MI WHI without Randomized 58. non-fatal MI WINS 2006 Randomized 2. aged 50-79 with CVD at other cancers.

nonfatal type 2 diabetes loss through myocardial to participate decreased infarction.a combined infarction. Summary of Clinical Trials for Smoking Cessation Clinical Trials Methods Participants Intervention Outcomes Lung Health Randomized 5. nonfatal myocardial infarction. Study Program controlled trial smoking COPD. stroke community-based intervention of cessation of smoking and increased physical activity. CV Death program versus usual care MRFIT Randomized 12. BP and smoking cessation OSLO Study Randomized 1232 high risk diet and Total mortality. lung cessation cancer. CV deaths Oslo men cessation Table 1. Summary of Clinical Trials on Exercise Clinical Trials Methods Participants Intervention Outcomes LOOK Ahead Randomized 5. program revascularization aimed at and total mortality lowering serum cholesterol. controlled trial multifactor Fatal and nonfatal intervention MI. .2.2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines 65 Table 1. trial arterial disease walking” regime myocardial .3. caloric intake and nonfatal stroke. CV deaths trial Oslo men Fowler et Randomized 882 men with A “stop smoking Maximum al/2002 controlled early peripheral and keep walking distance. CV controlled middle-aged cessation Events. or increased physical hospitalization for activity angina (composite) STENO2 Randomized 160 diabetic Stepwise Composite of controlled patients with implementation of death from trial microalbuminuria exercise program cardiovascular causes. revascularization.145 overweight Intensive lifestyle Death from controlled or obese intervention that cardiovascular trial patients with promoted weight causes. CV controlled trial middle-aged smoking Events.866 men In-depth CV mortality. nonfatal stroke. stroke.887 patients Intensive Total mortality. Chengdu trial Randomized 1232 high risk diet and smoking Total mortality. and amputation.

4. total cholesterol Intervention: 40 mg TC – 200. mg of lovastatin TC – 184 (17%) Unstable angina total cholesterol 4-65-6. body mass index < 32 kg/m2.0 mmol/L.52 mmol/L.8 (22%) IMT of carotid and controlled Trials < 8. fasting LDL Intervention: 40 mg TC .16 mmol/L for men.é 12% revascularization no serious ECG abnormalities according 5 years Any death to Minnesota code 1 (pathologic Q waves). TC/ HDL ratio >6 Coronary heart disease Intervention: 20-40 mg of lovastatin mortality Control: placebo Coronary revascularization Cardiovascular events Coronary events 2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines . and no history of myocardial infarction or other serious illness. Control: placebo LDL-C 115 (24%) Sudden cardiac death 4. Follow – up: 5 years TG – 143 Cardiovascular HDL-C ≤ 1.0 mmol/L. men aged 45-73 years old.Table 1.5-fold the laboratory upper normal Stroke limit Coronary revascularization AFCAPS/ Randomized 6605 participants. LDL-C > 4. HDL-C ≤ 1.36. LDL-C 3. arrhythmia such as atrial fibrillation. aged 45-64 years old.91 mmol/L.82 mmol/L.ê 20% Non-fatal MI 1995 controlled Trial cholesterol level of at least 4 mmol/L during the of pravastatin LDL-C ê 26% CHD death second and third visits. Intervention: 20-40 After 1 year Fatal and non-fatal MI TexCAPS 1998 controlled Trials postmenopausal women aged 55-73 years old.5 Myocardial infarction [ALT] and aspartate aminotransferase [AST]) not Follow-up: 3 years TG – 132. Follow-up: TG . Summary of Clinical Trials in the Use of Statins in Primary Prevention 66 Study/Year Method Participants Intervention Outcomes WOSCOPS Randomized 6595 men. although men with stable angina who had not been hospitalized within the previous 12 months KAPS 1995 Randomized 447 men.25 mmol/L.5 mmol/L and one value of ≤6.7 Cardiac death exceeding 1.3 (31%) femoral arteries and liver enzymes (alanine aminotransferase Control: placebo HDL-C 42. of pravastatin LDL-C 131. with at least one value Control: placebo HDL-C é 5% Coronary of ≥4. triglyceride ≤ HDL-C 39 mortality 4.22 mmol/L for women.

ratio of TC/ HDL ≥6. Intervention: 40 mg After 4 years Cardiovascular 2004 controlled Trial persistent microalbuminuria (a urinary albumin of pravastatin TC – 185. 3866 intervention). aged step I diet plus 20 TC – 208. type 2 DM.2 Angina I diet TG – 107 Stroke Follow-up: 5 years Sudden cardiac death 2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines Coronary revascularization JUPITER 2008 Randomized 17. or 5. total HDL-C 50. 55 years or older.7 (24%) Myocardial infarction urine sample and a concentration of 15 to 300 and/ or myocardial mg/24 hours in 2 24-hour urine samples at least Follow-up: 4 years ischemia once). not currently Follow-up: 3.4 (23%) myocardial infarction 5. PAD. blood pressure 160/100 mm Hg and no Heart failure use of antihypertensive medication.98 mmol/L Control: NCEP step HDL-C 62.5 mmol/L or lower. or treated HPN (SBP Control: placebo LDL-C 88 (34%) CHD ≥140 mmHg or DBP ≥90mmHg or both). other specified abnormalities on ECG. with Intervention: 10 mg After 3 years Primary: 2003 controlled Trials either untreated HPN (SBP ≥160 mmHg or DBP of atorvastatin TC – 161. LDL-C <3. and a total Peripheral vascular cholesterol level 8.5 years TG – 116. male sex.Study/Year Method Participants Intervention Outcomes ASCOT-LLT Randomized 10.6 mmol/L of rosuvastatin LDL-C 55 (49%) Non-fatal stroke Control: placebo HDL-C 50 Hospitalization for Follow-up: 1.0 mmol/L in disease case of previous myocardial infarction. triglyceride <5.99 unstable angina Coronary 67 revascularization Cardiovascular mortality . at least 3 CV risk factors (LVH. MEGA 2006 Randomized 7832 Japanese men and post-menopausal Intervention: NCEP After 9 years Coronary heart disease controlled Trial women (3966 control. smoking.9 (14%) Fatal and non-fatal 40-70 years old. 305 participants.9 years TG.0 mmol/L.802 participants.69-6. premature family history of CHD PREVEND IT Randomized 864 participants. total cholesterol concentration mg of pravastatin LDL-C 122.8 taking statin or fibrate. previous stroke or TIA. microalbuminuria or proteinuria.4 mmol/L.3 (17%) mortality concentration 10 mg/L in 1 early morning spot Control: placebo LDL-C 119. and no Stroke use of lipid-lowering medication.2 cholesterol of 6. aged 28-75 years old. aged 40-79 years old.4 (24%) Non-fatal MI and fatal ≥100 mmHg or both). hsCRP Intervention: 20 mg After 4 years Non-fatal MI controlled Trial ≥ 2 mg/L.

1 years GISSI.512 Low-intensity statin Pravastatin 40 mg 4. 200669 Randomized Controlled Trial 54 High-intensity statin Atorvastatin 20 mg 54 1 year .5 months (ALLIANCE)61 Lemos et al.9 years (SPARCL)58 Athyros et al. 68 Study Name Method Intervention Intervention Comparison group (N) Follow-up group (N) Intervention details Trials on individuals with ASCVD 4S. 1999 Randomized Controlled Trial 10.502 6. 1996 Randomized Controlled Trial 2.4 years statin LIPID. 2002 Randomized Controlled Trial 800 High-intensity statin Atorvastatin 20 mg 800 Mean 3 years (GREACE)59 Byington et al.365 High-intensity statin Atorvastatin 80 mg 2.078 5 years (CARE)66 Shepherd et al.221 Medium-intensity Simvastatin 20 mg 2.269 Medium-intensity Simvastatin 40 mg 10. 2002 Randomized Controlled Trial 2. 199455 Randomized Controlled Trial 2.081 Low-intensity statin Pravastatin 40 mg 2. 199856 Randomized Controlled Trial 4.133 Mean 23 months Amarenco et al.913 Mean 3.2 years (PROSPER)67 Shukla et al.217 High-intensity statin Atorvastatin 80 mg 1. 200057 Randomized Controlled Trial 2. 200568 Randomized Controlled Trial 75 Medium-intensity Atorvastatin 10 mg 75 1 years statin 2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines Sola et al. 1995 Randomized Controlled Trial 75 Low-intensity statin Pravastatin 40 mg 76 3 years (PLAC II)60 Koren et al. 2006 Randomized Controlled Trial 2.366 Median 4.138 Low-intensity statin Pravastatin 20 mg 2.5 Summary of Clinical Trials in the Use of Statins in Secondary Prevention.267 5 years (HPS)63 statin Pitt et al. 2004 Randomized Controlled Trial 1.223 5. 2003 Randomized Controlled Trial 844 Medium-intensity Fluvastatin 80 mg 833 3-4 years (LIPS)62 statin Meade et al.225 Mean 51.891 Low-intensity statin Pravastatin 40 mg 2. 199965 Randomized Controlled Trial 187 Low-intensity statin Fluvastatin 40 mg 178 1 year Sacks et al. 1995 (PLAC Randomized Controlled Trial 206 Low-intensity statin Pravastatin 40 mg 202 3 years I)64 Rieggeret al.Table 1.

6 mmol/L.0 years 2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines T1/T2 statin LIPID. 2000 (SCAT)70 Randomized Controlled Trial 230 Low-intensity statin Simvastatin 10 mg 230 3 . 60 years. MI or statin IP. LDL-C 2. 200771 Randomized Controlled Trial 19 Medium-intensity Atorvastatin 10 mg 19 3 years statin Yokoi et al. AP=angina pectoris. 200377 Randomized Controlled Trial 542 Low-intensity statin Pravastatin 40 mg 535 6. MI. MI or statin AP.3 mmol/L. 200376 Randomized Controlled Trial 972 Medium-intensity Simvastatin 40 mg 1009 5. UAP=unstable angina 69 pectoris. LDL-C 3. 199773 Randomized Controlled Trial 105 Medium-intensity Simvastatin 20 mg 97 5.0 years T2. Baseline TC 5. LDL-C 3. LDL-C 4. MI=myocardial infarction.5 years Yamada et al.9 mmol/L CARE.0 years T1/T2. Baseline TC 5.7 mmol/L. 63 years. 199875 Randomized Controlled Trial 282 Low-intensity statin Pravastatin 40 mg 304 5.4 years T1/T2. 64 years. Study Name Method Intervention Intervention Comparison group (N) Follow-up group (N) Intervention details Teo et al.6 mmol/L HPS. Baseline TC 6. 200572 Randomized Controlled Trial 186 Low-intensity statin Pravastatin 20 mg 187 3 years Trials on patients with diabetes mellitus 4S. T2=Type 2 diabetes.7 mmol/L T1=Type 1 diabetes. 200674 Randomized Controlled Trial 252 Medium-intensity Atorvastatin 10 mg 253 4.9 mmol/L.0 years T1/T2. Baseline TC 4. 61 years. IP=interventional procedure.8 mmol/L ASPEN. MI or UAP. .

3% with a TC mg/dL Gemfibrozil 600 5 years MI (fatal and history of DM (N=135).5 mg/dL fenofibrate 200 mean 100% DM.5 mg/dL 400 mg/day sudden death HDL 34. years without history of CV disease LDL 118 mg/dL mg per day non-fatal MI 22% with history of CV disease (combined HDL 42.6. 48% with CVD (combined primary & HDL 39.3 mg/dL Bezafibrate 400 3 years Change in the carotid (1998) without history of clinical CV disease LDL 141.5 mg/dL years percentage stenosis FIELD (2005) 9795 Type 2 diabetes patients. Summary of Clinical Trials Using Fibrates in Individuals with Diabetes 70 Study/year Population Baseline lipid values Intervention Duration of Outcome Measures Mean (SD) mg/dL follow up INCLUDED SENDCAP 164 Type 2 diabetes patients.51 (0. mean age of 62 TC 194 mg/dL Fenofibrate 200 5 years CHD death.5 mg/dL mg/day of nonfatal MI & HDL 34. secondary prevention) TG 229.Table 1.1 years Combined incidence subjects with DM (N= 769) with CV disease LDL 147.1 mg/dL VA-HIT (2002) Men with average age of 64 years. Fatal and Non-fatal MI 0.72) incidence of CHD DAIS (2001) 418 diabetic patients. 25% of TC 213.1 mg/dL HHS (1987) Men with an average age of 47 years. without CV disease LDL mg/dL mg/day nonfatal).5 mg/dL byB-mode ultrasound.3 years Mean segment diameter.5 mg/dL years (IMT) measured Primary prevention study TG 198.0 mg/dL mg/day for 3 lumen diameter.2 years MI (fatal and nonfatal).200 5.3 mg/dL mg OD for 3 intima-media thickness HDL 39. 35 to 65 years old TC 223. analysis). 40 to 65 years old with or TC 3301. mg/dL Micronized 3. without previous coronary intervention LDL 130.2 mg/dL Bezafibrate 6.2 mg/dL Gemfibrozil 1.5 mg/dL Secondary Prevention study TG 156. HDL mg/dL cardiac death 2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines Primary Prevention study TG mg/dL .2. mean age of 60 years LDL 147.5 mg/dL death from CAD Secondary Prevention study TG 156.5 mg/dL primary & secondary prevention) TG 154 mg/dL REVIEWED BUT EXCLUDED BIP (2000) 10% with history of diabetes (N=309) (subgroup TC 213.10.

the not taking statin outcome for therapy at study prespecified entry subgroup analyses was total cardiovascular events (the composite of cardiovascular death. MLD of the tenosis. and infarction). FIELD/2005 9. all-cause mortality Rubins/1999 2. transient ischemic attack. Change from the no mortality (LOCAT) ninety-five men releasegemfibrozil baseline to the ≤70 years old (Lopid SR) follow-up angiogram post CABG 1200 mg/d or a in the ADS and with lipid (197 matching placebo. and hospitalization for unstable angina or congestive heart failure. carotid endarterectomy.and coronary and carotid revascularisation . with infarction or death lipid criteria from coronary heart disease.7 Summary of Clinical Trials in the Use of Fibrates in Patients in Established ASCVD Study/Year Population Intervention Outcomes Remarks Frick/1997 Three hundred slow.795 micronised Primary outcome 2131 with participants fenofibrate 200 was coronary events previous aged 50–75 mg daily (n=4895) (coronary heart cardiovascular years. death from any cause. myocardial infarction. stroke. stroke. with or matching disease death or disease and type 2 diabetes placebo (n=4900) non-fatal myocardial 7664 without mellitus. revascularization procedures.531 men with gemfibrozil (1200 Combined (VA-HIT) coronary heart mg per day) vs incidence of disease <74 yr placebo nonfatal myocardial old CHD.2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines 71 Table 1. intervention vs changes in the 198) primary segments.

72 Table 1. Within 24 hours Pravastatin 20-40 mg 1710 Placebo 1698 30 days 2004 PACT Schwartz. 1997 Within 48 hours Pravastatin 10-20 mg 36 Placebo 33 3 months PAIS 2001 Within 48 hours Pravastatin 40 mg 50 Placebo 49 3 months PTT. 2002 Within 24 hours Pravastatin 40 mg 79 Usual Care 85 4 months LIPS.8 Summary of Clinical Trials in the Use of Statins in Patients with ACS Study Name Intervention: 1: Intervention 1: Number Comparison Number Follow-up timing details randomised randomized intervention comparison group group De Lemos. 2004 Within 5 days Simvastatin 40 mg for 2265 Placebo for 4 months 2232 2 years Phase Z of A 1 month then 80 mg then simvastatin 20 mg to Z Thompson. 2004 24-96 hours Atorvastatin 80 mg 1538 Placebo 1548 First 16 weeks MIRACL Musashi-AMI Within 96 hours Any Statin 241 No statin 245 Up to 24 months LAMIL. 2002 Within 48 hours Fluvastatin 80 mg 844 Placebo 833 45 months ESTABLISH. Within 24 hours Atorvastatin 20 mg 35 Usual Care 35 6 months 2004 FACS. 2010 Within 24 hours Fluvastatin 80 mg 78 Placebo 78 1 year 2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines .

836). sudden death. n=2. Summary of Clinical Trials using Omega 3 Fatty Acids in Patients with Dyslipidemia Study/Year Population Intervention Outcomes Remarks Galan/2011 2501 patients with a Daily dietary supplement containing Major cardiovascular events. vitamin E (300 mg Death. or angina. both (n=2830). Around <30% are 2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines angiographically proven fatal and nonfatal MI. and vitamin B-12 (20 μg) or myocardial infarction. or ischaemic placebo. non-fatal myocardial Open label study PREVENZIONE/1999 recent (<3 months daily. About 30% are on (n=3481) cardiovascular mortality or admission rosuvastatin for any reason. on statins coronary artery disease PUFA CABG 2005 160 patients for CABG 79 PUFA vs 81 control Occurence of atrial fibrillation and Open label cardiovascular events CVE. history of myocardial 5-methyltetrahydrofolate (560 μg). mortality 73 . or none infarction. and stroke GISSI 11 324 patients surviving 1 g daily.830). stroke. unstable B-6 (3 mg). CHF. vitamin defined as a composite of non-fatal infarction.9. and stroke myocardial infarction (control. sudden cardiac death. and containing omega 3 fatty death from cardiovascular disease stroke acids (600 mg of eicosapentanoic acid and docosahexaenoic acid at a ratio of 2:1) or placebo.7 years. Cause of HF is admission for cardio vascular ischemic in 50% reasons.Table 1. GISSI HF/2008 CHF II-IV n-3 PUFA 1 g daily (n=3494) or placebo Cardiovascular mortality. admission for any reason. n=2. admission for heart failure. Median duration of supplementation was 4. n=2828) for 3·5 years SCIMO/1999 223 patients with 112 PUFA vs 111 placebo CAD progression. myocardial infarction.

assessed with: reduction of fat vs control diet) 65508 no no serious Serious no serious Undetected ⊕⊕⊕⊝ 2867/37402 2020/28106 RR 0.86 Study population (31 studies) serious inconsistency imprecision MODERATE (7.Appendix 2.2%) (0. assessed with: reduction of dietary fat vs control diet) 71790 no no serious Serious1 no serious Undetected ⊕⊕⊕⊝ 2404/40957 1888/30833 RR 0.7%) (7.93 to 11 years risk of due to 1.96) 77 per 11 fewer bias indirectness 1000 per 1000 (3 fewer to 16 fewer) Moderate Total mortality (CRITICAL OUTCOME.79 to 8 years risk of due to 0.04) 59 per 1 fewer bias indirectness 1000 per 1000 (4 fewer to 2 more) Moderate 2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines . 2012 May 16.9%) (6.1 Grade Pro Summary of Evidence on Reduction of Trans/Modified Fat Bibliography: Cochrane Database Syst Rev.98 Study population (21 studies) serious inconsistency imprecision MODERATE1 (5. GRADE Pro Tables 74 Table 2.1%) (0.5:CD002137 Quality assessment Summary of Findings Participants Risk of Inconsistency Indirectness Imprecision Publication Overall Study event rates (%) Relative Anticipated absolute (studies) bias bias quality of effect effects Follow up evidence (95% CI) (6 months duration) With Control With Risk Risk Reduced with difference dietary fat Control (95% CI) Major Acute Coronary Event(MACE) (CRITICAL OUTCOME.

72 to 8 years risk of due to 1.04) 20 per 1 fewer bias indirectness 1000 per 1000 (3 fewer to 1 more) Moderate Fatal and Nonfatal MI (CRITICAL OUTCOME.Cardiovascular mortality (CRITICAL OUTCOME.94 Study population (16 studies) serious inconsistency imprecision MODERATE1 (2%) (2. assessed with: reduction of dietary fat vs control) 59853 no no serious Serious1 no serious Undetected ⊕⊕⊕⊝ 457/25063 683/34790 RR 0.2%) (3.84 to 11 years risk of due to 1.89 to 8 years risk of due to 1.11) 18 per 0 fewer per 1000 indirectness 1000 (from 2 fewer to 2 2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines bias more) Moderate - 1 No Filipinos included in the study population 75 .8%) (2%) (0. assessed with: reduction of fat in diet) 64891 no no serious Serious1 no serious Undetected ⊕⊕⊕⊝ 894/27611 1174/37280 RR 0.2%) (0. assessed with: reduced/modified fat vs usual diet) 65978 no no serious Serious1 no serious Undetected ⊕⊕⊕⊝ 774/37840 633/28138 RR 0.11) 32 per 3 fewer per 1000 bias indirectness 1000 (from 9 fewer to 4 more) Moderate - Stroke (CRITICAL OUTCOME.99 Study population (11 studies) serious inconsistency imprecision MODERATE1 (1.90 Study population (19 studies) serious inconsistency imprecision MODERATE1 (3.1%) (0.

2 GRADE PRO summary of evidence on the benefit of smoking cessation 76 Quality assessment Summary of Findings Participants Risk of Inconsistency Indirectness Imprecision Publication Overall Study event rates (%) Relative Anticipated absolute (studies) bias bias quality of effect effects Follow up evidence (95% CI) With Control With Risk with Risk Smoking Control difference cessation with Smoking cessation (95% CI) Total mortality (CRITICAL OUTCOME) 18023 no no serious serious1 no serious Undetected ⊕⊕⊕⊝ 918/9030 826/8993 RR 0.4%) (2.2%) (0.2%) (9.82 to 7 years risk of due to 0.76 to 7 years risk of due to 1.Table 2.99) 102 per 10 fewer bias indirectness 1000 per 1000 (from 1 fewer to 18 fewer) Cardiovascular deaths (CRITICAL OUTCOME) 18023 no no serious serious1 no serious Undetected ⊕⊕⊕⊝ 219/9030 200/8993 RR 0.92 Study population (2 studies) serious inconsistency imprecision MODERATE1 (2.2%) (0.11) 24 per 1000 2 fewer per bias indirectness 1000 (from 6 fewer to 3 more) 2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines .90 Study population (3 studies) serious inconsistency imprecision MODERATE1 (10.

6%) (5.6%) (0. 2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines 77 .85 Study population (3 studies) serious inconsistency imprecision MODERATE1 (6. Quality assessment Summary of Findings Participants Risk of Inconsistency Indirectness Imprecision Publication Overall Study event rates (%) Relative Anticipated absolute (studies) bias bias quality of effect effects Follow up evidence (95% CI) With Control With Risk with Risk Smoking Control difference cessation with Smoking cessation (95% CI) CV Events (CRITICAL OUTCOME 18023 no no serious serious1 no serious undetected ⊕⊕⊕⊝ 599/9030 506/8993 RR 0.76 to 7 years risk of due to 0.95) 66 per 1000 10 fewer bias indirectness per 1000 (from 3 to 16 fewer) 1 No Filipinos included in the study.

75 Study population (2 studies) serious inconsistency imprecision MODERATE1.4%) (0.7%) (0.5%) (6.2 (20.5%) (0.09) 160 per 5 fewer per of bias. assessed with: Moderate exercise versus usual care) 5305 no no serious serious2 no serious undetected ⊕⊕⊕⊝ 226/2655 170/2650 RR 0.2 (8.Table 2.7%) (19.2 (16%) (15.97 Study population (2 studies) inconsistency imprecision LOW1.62 to 9 years risk of due to 0.95 Study population (2 studies) serious inconsistency imprecision MODERATE1. 1000 1000 indirectness (from 24 fewer to 14 more) Major Acute Coronary Event (CRITICAL OUTCOME. assessed with: Moderate exercise versus usual care) 5305 serious1 no serious serious2 no serious undetected ⊕⊕⊝⊝ 425/2655 410/2650 RR 0.91) 85 per 21 fewer per bias1 indirectness 1000 1000 (from 8 fewer to 32 fewer) Moderate - 2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines . Grade PRO Summary of Evidence on the Benefit of Exercise 78 Quality assessment Summary of Findings Participants Risk of Inconsistency Indirectness Imprecision Publication Overall quality Study event rates (%) Relative Anticipated absolute (studies) bias bias of evidence effect effects Follow up (95% CI) With With Risk with Risk diff with Control Exercise Control Exercise (95% CI) All cause mortality (CRITICAL OUTCOME.3.85 to 9 years due to risk 1.05) 207 per 10 fewer per bias1 indirectness 1000 1000 (from 29 fewer to 10 more) CV Mortality (CRITICAL OUTCOME. assessed with: Moderate exercise vs usual care) 6027 no no serious serious2 no serious undetected ⊕⊕⊕⊝ 624/3016 594/3011 RR 0.86 to 9 years risk of due to 1.

15) 109 per 1 fewer per bias 1000 1000 (from 17 fewer to 16 more) 79 . assessed with: Moderate exercise versus advice) 5305 serious1 no serious serious2 no serious undetected ⊕⊕⊝⊝ 100/2655 88/2650 RR 0. assessed with: Moderate exercise versus usual advice) 160 serious1 no serious serious2 no serious undetected ⊕⊕⊝⊝ 17/80 5/80 RR 0. 1000 1000 indirectness (from 51 fewer to 189 fewer) Stroke (CRITICAL OUTCOME. Quality assessment Summary of Findings Participants Risk of Inconsistency Indirectness Imprecision Publication Overall quality Study event rates (%) Relative Anticipated absolute (studies) bias bias of evidence effect effects Follow up (95% CI) With With Risk with Risk diff with Control Exercise Control Exercise (95% CI) Non-fatal MI (CRITICAL OUTCOME.99 Study population MODERATE1 2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines (2 studies) inconsistency indirectness imprecision (10. 1000 1000 indirectness (from 12 fewer to 6 more) Revascularization (CRITICAL OUTCOME.11 to due to risk 0.17) 38 per 5 fewer per of bias.3%) (0.7%) (0.67 to 9 years due to risk 1.29 Study population (1 study) inconsistency imprecision LOW1.9%) (10.2 (3.3%) (6.8%) (3. assessed with: Exercise versus usual care) 5312 serious1 no serious no serious no serious undetected ⊕⊕⊕⊝ 289/2659 284/2653 RR 0.2 (21.3%) (0.88 Study population (2 studies) inconsistency imprecision LOW1.84 to 9 months due to risk of 1.76) 212 per 151 fewer per of bias.

72 to 1000 (from MODERATE 0.67 5 fewer per ⨁⨁⨁◯ CRITICAL trials serious (1.70) 7 fewer to 11 fewer) 2.6%) (3.9% 11 fewer per 1000 (from 9 fewer to 13 2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines fewer) .90) 3 fewer to 9 fewer) 3.79) 3 fewer to 6 fewer) 0.4.4%) (0.5%) (2.0%) (1.9% 3 fewer per 1000 (from 2 fewer to 4 fewer) Myocardial infarction 7 randomised not not serious serious  1 not serious none 367/25198 598/25252 RR 0.2%) (0. GRADE PRO Summary of Evidence on the benefit of statins for primary prevention 80 Quality assessment № of patients Effect № of Study Risk of Inconsistency Indirectness Imprecision Other Relative Absolute Quality Importance Statins placebo (95% studies design bias considerations CI) (95% CI) Total mortality 4 randomised not not serious serious  1 not serious none 544/21237 673/21297 RR 0.4%) (0.Table 2.81 6 fewer per ⨁⨁⨁◯ CRITICAL trials serious (2.57 to 1000 (from MODERATE 0.4% 7 fewer per 1000 (from 3 fewer to 10 fewer) Cardiovascular death 7 randomised not not serious serious  1 not serious none 240/25198 357/25252 OR 0.54 to 1000 (from MODERATE 0.61 9 fewer per ⨁⨁⨁◯ CRITICAL trials serious (1.

7%) (3.79) (from 14 fewer to 22 fewer) 3.0%) (1.67 to per 1000 LOW 0.63 to 1000 (from MODERATE 0.65 to per 1000 MODERATE 0.71 11 fewer ⨁⨁⨁◯ IMPORTANT trials serious (2.6% 10 fewer per 1000 (from 8 fewer to 12 fewer) Coronary revascularization 2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines 6 randomised not not serious serious  1 not serious none 660/24765 925/24821 RR 0.88) 2 fewer to 5 fewer) 1.73 18 fewer ⨁⨁◯◯ CRITICAL trials serious (4.3% 7 fewer per 1000 (from 81 5 fewer to 8 fewer) .4%) (0.6% 4 fewer per 1000 (from 2 fewer to 6 fewer) Cardiovascular events 4 randomised not serious  2 serious  1 not serious none 1028/21239 1411/21305 RR 0.7%) (0.78) (from 8 fewer to 13 fewer) 2.74 4 fewer per ⨁⨁⨁◯ CRITICAL trials serious (1.6%) (0.Quality assessment № of patients Effect № of Study Risk of Inconsistency Indirectness Imprecision Other Relative Absolute Quality Importance Statins placebo (95% studies design bias considerations CI) (95% CI) Stroke 6 randomised not not serious serious  1 not serious none 227/21894 306/21951 RR 0.8%) (6.

98 0 fewer ⨁⨁⨁◯ CRITICAL trials serious (1.6%) (0.64 to per 1000 MODERATE 0.53 to per 1000 MODERATE 1.7%) (3. GRADE PRO Summary of Evidence in the use of Statin in Diabetes without ASCVD. 82 Quality assessment № of patients Effect Relative Quality Importance № of Study Risk of Other Absolute Inconsistency Indirectness Imprecision Statins Placebo (95% studies design bias considerations (95% CI) CI) Total Mortality 1 randomised not not serious serious1 not serious none 61/1428 82/1409 RR 0.Table 2.8%) (0.01) (from 1 more to 27 fewer) Fatal CHD/Cardiovascular death 3 randomised not not serious serious2 not serious none 60/3645 58/3629 RR 0.5.83) (from 6 fewer to 13 fewer) 2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines .7%) (0.73 10 fewer ⨁⨁⨁◯ CRITICAL trials serious (2.41) (from 5 fewer to 7 more) Fatal and Non-fatal MI 4 randomised not not serious serious3 not serious none 378/13914 518/13896 RR 0.6%) (1.3%) (5.68 to per 1000 MODERATE 1.73 16 fewer ⨁⨁⨁◯ CRITICAL trials serious (4.

6%) (2. However.84 5 fewer ⨁⨁⨁◯ IMPORTANT trials serious (2.1%) (0. None of the studies included Filipinos or were done locally . All the studies except for HPS.78 21 fewer ⨁⨁⨁⨁ CRITICAL trials serious association (7.4%) (9.75 5 fewer ⨁⨁⨁◯ CRITICAL trials serious (1. All the studies except for ASCOT were done on DM but none were done locally or included Filipinos 83 5. All the studies are on DM but none were done locally or included Filipinos 3.97) (from 1 2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines fewer to 8 fewer) RR=relative risk 1.0%) (0.89) (from 2 fewer to 8 fewer) Acute Major CVD Events (composite) 8 randomised not not serious serious5 not serious strong 597/8083 766/8012 RR 0.6%) (0.86) (from 13 fewer to 29 fewer) Coronary revascularization (Interventional) Procedures 3 randomised not not serious serious5 not serious none 328/12908 390/12875 RR 0.63 to per 1000 MODERATE 0.7 to per 1000 HIGH (7) 0. NONE of these studies were done locally or included Filipinos 4.Quality assessment № of patients Effect Relative Quality Importance № of Study Risk of Other Absolute Inconsistency Indirectness Imprecision Statins Placebo (95% studies design bias considerations (95% CI) CI) CVD/Stroke 4 randomised not not serious serious5 not serious none 224/13914 298/13896 RR 0.5%) (3.73 to per 1000 MODERATE 0. No explanation was provided 2. were done on DM patients.

09 6 more ⨁⨁⨁◯ CRITICAL trials serious association (7.8%) (2.5%) (0.09 2 more ⨁⨁⨁◯ CRITICAL trials serious association (2.2%) (3.8%) (0.4%) (0.Table 2.0%) (6.73 per 1000 LOW -0.85 10 fewer ⨁⨁◯◯ CRITICAL trials serious (5.87 to per 1000 MODERATE 1.6 GRADE PRO Summary table for the Use of Fibrates for the Primary Prevention of Cardiovascular Events Among Diabetic Individuals.26) (from 4 fewer to 17 more) Cardiac Mortality 3 randomised not not serious serious 1 serious 2 strong 143/5183 132/5194 RR 1.6%) (0. DAIS & SENDCAP are small studies .37) (from 4 fewer to 9 more) Stroke 1 randomised not not serious serious 1 not serious none 158/4895 175/4900 RR 1.8%) (6.4) (from 5 fewer to 14 more) Major adverse CV events 3 randomised not not serious serious 1 serious 2 none 300/5183 355/5194 RR 0.1 4 more ⨁⨁⨁◯ CRITICAL trials serious (3. None of the trials involved Asians specifically Filipinos 2.98) (from 1 fewer to 18 fewer) MD = mean difference. RR – relative risk 2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines 1. 84 Quality assessment № of patients Effect № of Study Risk of Other Relative Absolute Quality Importance studies design bias Inconsistency Indirectness Imprecision considerations Fibrates Placebo (95% CI) (95% CI) Total mortality 3 randomised not not serious serious 1 serious 2 strong 362/5183 333/5194 RR 1.94 to per 1000 MODERATE 1.86 to per 1000 MODERATE 1.

83 to per 1000 MODERATE 0.91) (from 10 fewer to 19 fewer) Fatal coronary heart disease or cardiovascular death 14 randomized not not serious serious 1 not serious none 1812/29980 2287/29969 RR 0.78 11 fewer ⨁⨁⨁◯ CRITICAL trials serious (4. different socio-economic population (first world vs third world) 2 Heterogeneity I2=57% . RR=relative risk.7 GRADE PRO Summary of evidence on the use of statins for secondary prevention in individuals with ASCVD.75 to per 1000 MODERATE 0.9%) (11.3%) (0.75) (from 18 fewer to 25 fewer) 2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines Stroke 11 randomized not not serious serious 1 not serious none 1060/26221 1356/26205 RR 0. Quality assessment № of patients Effect № of Risk of Other Relative Absolute Quality Importance Study design Inconsistency Indirectness Imprecision statins placebo studies bias considerations (95% CI) (95% CI) Total mortality 15 randomized not not serious serious 1 not serious none 2978/30085 3436/30081 RR 0.2%) (0.87 15 fewer ⨁⨁⨁◯ CRITICAL trials serious (9.0%) (5.Table 2. Asians were not well-represented.84) (from 8 fewer to 14 fewer) ASCVD=atherosclerotic cardiovascular disease.79 16 fewer ⨁⨁⨁◯ CRITICAL trials serious (6.72 to per 1000 MODERATE 0.70 22 fewer ⨁⨁◯◯ CRITICAL trials serious (5. 1 85 Caucasian population.6%) (0.0%) (7.84) (from 12 fewer to 19 fewer) 1 Myocardial infarction 13 randomized not serious 2 serious 1 not serious none 1377/27009 1960/27009 RR 0.66 to per 1000 LOW 0.1%) (7.4%) (0.

92) (from 6 fewer to 15 fewer) Stroke 3 randomized not not serious serious 1 not serious none 388/12735 439/12714 ⨁⨁⨁◯ CRITICAL RR 0.0%) (3.88 4 fewer trials serious (3.0%) (0.5%) (5. RR=relative risk.78 to per 1000 MODERATE 0.03) (from 2 more to 8 fewer) Myocardial infarction 4 randomized not not serious serious 1 not serious none 1058/17730 1247/17720 RR 0.92 to per 1000 MODERATE 1.98 2 fewer ⨁⨁⨁◯ CRITICAL trials serious (9.01) (from 0 fewer to 2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines 8 fewer) ASCVD.6%) (9.Table 2.8 GRADE Pro summary of evidence on the use of high-intensity (atorvastatin 80 or simvastatin 80 mg) vs medium-intensity (atorvastatin 10 mg or simvastatin 20 mg) statin therapy for secondary prevention in ASCVD 86 Quality assessment № of patients Effect high medium Quality Importance № of Study Risk of Inconsistency Indirectness Imprecision Other Relative Absolute intensity studies design bias considerations intensity (95% CI) (95% CI) statin statin Total mortality 4 randomized not not serious serious 1 not serious none 1678/17562 1711/17543 RR 0.87 to per 1000 MODERATE 1.77 to per 1000 MODERATE 1.5%) (0.95 3 fewer ⨁⨁⨁◯ CRITICAL trials serious (5.8%) (0. atherosclerotic cardiovascular disease.04) (from 4 more to 8 fewer) Cardiovascular mortality 4 randomized not not serious serious 1 not serious none 972/17730 1026/17720 RR 0.8%) (0. .0%) (7.85 11 fewer ⨁⨁⨁◯ CRITICAL trials serious (6.

86 to per 1000 MODERATE 1.94 to per 1000 MODERATE 1.2%) (3.5%) (0.8%) (0.37) (from 4 fewer to 9 more) Stroke 1 randomised not not serious serious 1 not serious none 158/4895 175/4900 RR 1.1 4 more ⨁⨁⨁◯ CRITICAL trials serious (3. RR = relative risk 87 1.85 10 fewer ⨁⨁◯◯ CRITICAL trials serious (5.26) (from 4 fewer to 17 more) Cardiac Mortality 3 randomised not not serious serious 1 serious 2 strong 143/5183 132/5194 RR 1.73 per 1000 LOW -0.09 6 more ⨁⨁⨁◯ CRITICAL trials serious association (7.6%) (0. None of the trials involved Asians specifically Filipinos 2.8%) (2.8%) (6.87 to per 1000 MODERATE 1.4%) (0. DAIS & SENDCAP are small studies .9.Table 2.09 2 more ⨁⨁⨁◯ CRITICAL trials serious association (2.98) (from 1 fewer to 18 fewer) MD = mean difference.0%) (6.4) (from 5 fewer to 14 more) 2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines Major adverse CV events 3 randomised not not serious serious 1 serious 2 none 300/5183 355/5194 RR 0. GRADE PRO Summary table for the Use of Fibrates for the Primary Prevention of Cardiovascular Events Among Diabetic Individuals. Quality assessment № of patients Effect № of Study Risk of Inconsistency Indirectness Imprecision Other Relative Absolute Quality Importance Fibrates Placebo studies design bias considerations (95% CI) (95% CI) Total mortality 3 randomised not not serious serious 1 serious 2 strong 362/5183 333/5194 RR 1.

7%) (25.Table 2.1%) (0.6%) (15.6% 28 fewer per 1000 (from 38 more to 79 fewer) 2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines .90 15 fewer ⨁⨁⨁◯ CRITICAL trials serious (13.69 to per 1000 MODERATE 1.76 to per 1000 MODERATE 1. Grade PRO Summary of Evidence in the Use of Fibrates as Alternative Treatment to Statin 88 Quality assessment № of patients Effect Quality Importance № of Study Risk of Inconsistency Indirectness Imprecision Other Relative Absolute Fibrates placebo studies design bias considerations (95% CI) (95% CI) All cause mortality 2 randomised not not serious serious  1 not serious none 199/1461 221/1465 RR 0.9% 9 fewer per 1000 (from 7 more to 21 fewer) CVE 2 randomised not not serious serious  1 not serious none 530/2332 597/2330 RR 0.6%) (0.15) (from 38 more to 79 fewer) 25.89 28 fewer ⨁⨁⨁◯ CRITICAL trials serious (22.08) (from 12 more to 36 fewer) 8.10.

0%) (0.55 to per 1000 MODERATE 1.6%) (14.07) (from 4 more to 27 fewer) 6.80 29 fewer ⨁⨁⨁◯ CRITICAL trials serious (11.Quality assessment № of patients Effect Quality Importance № of Study Risk of Inconsistency Indirectness Imprecision Other Relative Absolute Fibrates placebo studies design bias considerations (95% CI) (95% CI) Nonfatal MI 1 randomised not not serious serious  1 not serious none 146/1264 184/1267 RR 0.6%) (6.65 to per 1000 MODERATE 0.97) (from 4 fewer to 51 fewer) 14.76 14 fewer ⨁⨁⨁◯ CRITICAL trials serious (4.5%) (0.0% 14 fewer per 1000 2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines (from 4 more to 27 fewer) 89 .5% 29 fewer per 1000 (from 4 fewer to 51 fewer) Stroke 1 randomised not not serious serious  1 not serious none 58/1264 76/1267 RR 0.

7%) (0.02) (from 2 more to 36 fewer) 9.0%) (22.3% 20 fewer per 1000 (from 2 more to 36 fewer) Revascularization 1 randomised not not serious serious  1 not serious none 266/1264 287/1267 RR 0. 90 Quality assessment № of patients Effect Quality Importance № of Study Risk of Other Relative Absolute Fibrates placebo studies design bias Inconsistency Indirectness Imprecision considerations (95% CI) (95% CI) CHD death 1 randomised not not serious serious  1 not serious none 93/1264 118/1267 RR 0. 2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines . and intervention not tested in statin-intolerant patients.4%) (9.79 20 fewer ⨁⨁⨁◯ CRITICAL trials serious (7.3%) (0. Serious indirectness in two levels: lack of Filipino population.6% 16 fewer per 1000 (from 18 more to 45 fewer) 1.80 to per 1000 MODERATE 1.08) (from 18 more to 45 fewer) 22.61 to per 1000 MODERATE 1.93 16 fewer ⨁⨁⨁◯ IMPORTANT trials serious (21.

81 to per 1000 LOW 1. GRADE Pro Summary of Evidence for trials in the use of Statins in Patients with Acute Coronary Syndrome Quality assessment № of patients Effect № of Study Risk of Inconsistency Indirectness Imprecision Other Relative Absolute Quality Importance studies design bias considerations Statins Placebo (95% CI) (95% CI) Total Mortality 10 randomised not not serious serious1 not serious none 236/6872 295/6835 RR 0.8% 8 fewer per 1000 (from 2 fewer to 13 fewer) Cardiovascular death 8 randomised not not serious serious2 not serious none 114/5256 154/5209 RR 0.0%) (5.67 to per 1000 MODERATE 0.9% 7 fewer per 1000 (from 2 fewer to 12 fewer) 2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines Non-fatal MI 10 randomised not not serious serious2 serious3 none 344/6872 365/6835 RR 0.0% 3 fewer per 1000 91 (from 3 more to 8 fewer) .58 to per 1000 MODERATE 0.08) (from 4 more to 10 fewer) 4.80 9 fewer ⨁⨁⨁◯ CRITICAL trials serious (3.11.3%) (0.4%) (4.94) (from 2 fewer to 12 fewer) 2.3%) (0.74 8 fewer ⨁⨁⨁◯ CRITICAL trials serious (2.Table 2.0%) (0.94) (from 3 fewer to 14 fewer) 3.93 4 fewer ⨁⨁◯◯ CRITICAL trials serious (5.2%) (3.

06) (from 7 more to 17 fewer) 23.1%) (0.82 to per 1000 LOW 0.8%) (12.95 6 fewer ⨁⨁◯◯ IMPORTANT trials serious (11.0% 12 fewer per 1000 (from 14 more to 2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines 32 fewer) .94) (from 12 fewer to 35 fewer) 25.86 to per 1000 LOW 1.3%) (0.4%) (0.8%) (1.50 to per 1000 MODERATE 0.70 3 fewer ⨁⨁⨁◯ CRITICAL trials serious (0.99) (from 0 fewer to 6 fewer) 1.1% 30 fewer per 1000 (from 15 fewer to 45 fewer) Revascularization 8 randomised not not serious serious4 serious7 none 582/4925 609/4893 RR 0.0%) (19.Quality assessment № of patients Effect 92 № of Study Risk of Inconsistency Indirectness Imprecision Other Relative Absolute Quality Importance studies design bias considerations Statins Placebo (95% CI) (95% CI) Stroke 10 randomised not not serious serious4 not serious5 none 54/6872 78/6835 RR 0.0% 3 fewer per 1000 (from 0 fewer to 5 fewer) Major CV events 10 randomised not serious6 serious4 not serious none 1165/6872 1317/6835 RR 0.88 23 fewer ⨁⨁◯◯ CRITICAL trials serious (17.

82 trials serious (13.63 to 1000 (from LOW 1.13) 4 fewer to 8 fewer) 14.3% 26 fewer per 1000 (from 11 more to 53 fewer) Nonfatal MI 2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines 1 randomised not not serious serious  1 not serious none 102/4894 135/4876 3 fewer per ⨁⨁◯◯ CRITICAL RR 0.5%) (2. GRADEPRO Summary of Evidence in the Use of Omega 3 Fatty Acids as Alternative to Statin Quality assessment № of patients Effect Quality Importance № of Study Risk of Inconsistency Indirectness Imprecision Other Relative Absolute studies design bias considerations Fibrates placebo (95% CI) (95% CI) All cause mortality 2 randomised not not serious serious  1 not serious none 1250/7697 1368/7674 16 fewer per ⨁⨁◯◯ CRITICAL RR 0.7% 14 fewer per 1000 (from 2 more to 25 fewer) CV death 2 randomised not not serious serious  1 not serious none 848/6365 958/6345 27 fewer per ⨁⨁◯◯ CRITICAL RR 0.12.8%) (0.1%) (0.08) 12 more to 56 fewer) 14.3%) (15.8%) (0.70 to 1000 (from LOW 1.5% 3 fewer per 1000 (from 4 fewer to 8 93 fewer) .89 trials serious (2.99) 2 more to 29 fewer) 15.91 trials serious (16.Table 2.84 to 1000 (from LOW 0.2%) (17.

6%) (9.76 13 fewer per ⨁⨁◯◯ CRITICAL trials serious (4. 94 Quality assessment № of patients Effect Quality Importance № of Study Risk of Inconsistency Indirectness Imprecision Other Relative Absolute placebo studies design bias considerations Fibrates (95% CI) (95% CI) MACE 1 randomised not not serious serious  1 not serious none 345/4200 405/4188 RR 0.7%) (0. LOW 1.1% 8 fewer per 1000 (from 4 more to 27 fewer) Stroke 1 randomised not not serious serious  1 not serious none RR 1.79.07) 16 more to 34 fewer) 6. Serious indirectness in two levels: lack of Filipino population.97 ⨁⨁◯◯ IMPORTANT trials serious (0.97.20) 1. LOW 1.45) Revascularization 1 randomised not not serious serious  1 not serious none RR 0. 2015 Updated Clinical Practice Guidelines for the Management of Dyslipidemia in the Philippines .55 to 1000 (from LOW 1. and intervention not tested in statin-intolerant patients.19 ⨁⨁◯◯ CRITICAL trials serious (0.

a speakers’ bureau member. Dr. Sy is a consultant or advisory board member and has received honorarium from industry. Gobenchiong. Drs. Llanes is a member of the speakers’ bureau and has received honorarium and other forms of support from industry. Reganit. Merino. Serrano. Gonzales-Santos and Guerrero are members of the speakers’ bureau of various pharmaceutical companies. Dr. Te. Lazaro. Santiago-Halasan. Jamorabo-Ruiz. and Villaseñor-Andaman declared no potential conflicts of interest. Cheng is a member of the speakers’ bureau and has received honorarium from industry. Jimeno is a consultant or advisory board member of a pharmaceutical company. Dr. and speakers’ bureau member. and has received honorarium and other financial support from industry. Bongosia. Acuin is a consultant or advisory board member and has received honorarium from a non-industry organization. . Pestaño has received non-financial support from industry. Angus. Matawaran is a consultant or advisory board member. Duante and Toledo. Dr. Dr. from a pharmaceutical company. Dr. Dr. Cinco is a consultant or advisory board member. Dr. Gloria. and Drs. Caole-Ang. Ona. Olegario. Baello.DISCLOSURES Ms.