Clinical Pharmacy

Department

Clinical Pharmacy And

Drug Information
PL 504
Lecture 4
Interactive
Teaching

• OSCE
• Audio-visual learning
• Case studies
 References

• ACCP Updates in Therapeutics® 2020:

Pharmacotherapy Preparatory Review and
Recertification Course

• Walker, Roger, and Cate Whittlesea. Clinical

Pharmacy and Therapeutics. Edinburgh:
Churchill Livingstone, 2007.
 Lecture LOS
By the End of the lecture student will be able to
DYSLIPIDEMIA
Atherosclerosis is the pathologic process
of lipid accumulation and inflammation in the
vascular wall leading to vascular wall
thickening, luminal stenosis, and in some
cases thrombosis.

THE
LEADING
CAUSE TO
CAD
Diagnosis

Complete lipoprotein profile after 9–

12 hours of fasting preferred (i.e., TC,
LDL, HDL, and TG)

Lipoprotein (a) and Apolipoprotein B

are other tests that your care team may
be considered if you have early heart
disease or a strong family history of
early heart disease.
Goals of Therapy

1.Reduce CV morbidity and mortality

2.Achieve LDL-C goals, when appropriate

 A-Non-pharmacologic recommendations

Lifestyle modification is cornerstone of initial intervention

1. Heart-healthy diet
a. Recommend healthy diets such as the Dietary
Approaches to Stop Hypertension (DASH) diet or the
Mediterranean Diet

b. Emphasize consumption of fruits, vegetables, whole

grains, low-fat dairy products, skinless poultry and fish, nuts
and legumes, and non-tropical vegetable oils

c. Limit sweets, sugar-sweetened beverages, and red meats

d. Lower intake of saturated fats and replace with

unsaturated fats (especially polyunsaturated fats)
A-Non-pharmacologic recommendations

2. Regular exercise
Engage in moderate-to-vigorous intensity
aerobic physical activity 3-4 times per
week for an average of 40 minutes per
session

3. Smoking cessation
PHARMACOLOGICAL
 Pharmacologic recommendations
In general principles

a. First, initiate statin therapy if indicated. Optimize

statin therapy (high intensity or maximally tolerated
dose) before adding non-statin therapy

b. Second, add ezetimibe if indicated

c. Third, consider PCSK9-inhibitors (PCSK9-I)

 Pharmacologic recommendations
Therapy recommendations are divided into patient
management groups:
a. Secondary ASCVD prevention

b. Severe hypercholesterolemia (LDL-C ≥190 mg/dL)

c. Diabetes mellitus (DM)

d. Primary prevention
Clinical ASCVD consists of
ACS, those with history of MI, stable or
unstable angina or coronary other arterial
revascularization, stroke, transient
ischemic attack (TIA), or peripheral
artery disease (PAD) including aortic
aneurysm, all of atherosclerotic origin

Very high-risk includes

a history of multiple (≥ 2) major ASCVD
events or 1 major ASCVD event and
multiple (≥ 2) high-risk conditions
 Pharmacologic recommendations
Therapy recommendations are divided into patient
management groups:
a. Secondary ASCVD prevention

b. Severe hypercholesterolemia (LDL-C ≥190 mg/dL)

c. Diabetes mellitus (DM)

d. Primary prevention
LDL<50%
reduction
and/ Or
LDL ≥ 100
 Severe Hypercholesterolemia (LDL-C ≥190 mg/dL [≥4.9
mmol/L])

In patients 20 to 75 years of age with an LDL-C

level of 190 mg/dL or higher (≥4.9 mmol/L),
maximally tolerated statin therapy is recommended

In patients 20 to 75 years of age with an LDL-C

level of 190 mg/dL or higher (≥4.9 mmol/L) who
achieve less than a 50% reduction in LDL-C
while receiving maximally tolerated statin therapy
and/ OR have an LDL-C level of 100 mg/dL or
higher (≥2.6 mmol/L), ezetimibe therapy is
reasonable
 Severe Hypercholesterolemia (LDL-C ≥190 mg/dL [≥4.9
mmol/L])

 In patients 30 to 75 years of age with heterozygous FH

and with an LDL-C level of 100 mg/dL or higher (≥2.6
mmol/L) while taking maximally tolerated statin and
ezetimibe therapy, the addition of a PCSK9 inhibitor
may be considered.

 In patients 40 to 75 years of age with a baseline LDL-C

level of 220 mg/dL or higher (≥5.7 mmol/L) AND who
achieve an on-treatment LDL-C level of 130 mg/ dL or
higher (≥3.4 mmol/L) while receiving maximally
tolerated statin and ezetimibe therapy, the addition of a
PCSK9 inhibitor may be considered
 Pharmacologic recommendations
Therapy recommendations are divided into patient
management groups:
a. Secondary ASCVD prevention

b. Severe hypercholesterolemia (LDL-C ≥190 mg/dL)

c. Diabetes mellitus (DM)

d. Primary prevention
 Diabetic dyslipidemia

• Is characterized by elevated fasting and

postprandial triglycerides, low HDL-cholesterol,
elevated LDL-cholesterol and the
predominance of small dense LDL particles.

• These lipid changes represent the major link

between diabetes and the increased
cardiovascular risk of diabetic patients.
 Diabetic dyslipidemia

The underlying pathophysiology is only partially

understood.
• Alterations of insulin sensitive pathways
• increased concentrations of free fatty acids and
• low grade inflammation

all play a role and result in an overproduction and

decreased catabolism of triglyceride rich lipoproteins of
intestinal and hepatic origin.
 LDL-C ≥50%
LDL-C ≥50%
 Risk factors such as

• Dyslipidemia,
• Obesity,
• Inactive lifestyle,
• Hypertension,
• Smoking,
• Family history of ASCVD
• Metabolic syndrome
• Elevated C reactive protein
• CKD
 Diabetes Mellitus in Adults

 In adults 40 to 75 years of age with diabetes mellitus, regardless

of estimated 10-year ASCVD risk, moderate-intensity statin
therapy is indicated.

 In adults 40-75 with diabetes mellitus who have multiple ASCVD risk factors, it
is reasonable to prescribe high-intensity statin therapy with the aim to reduce
LDL-C levels by 50% or more

 In adults 40-75 with diabetes mellitus and 10-year ASCVD risk

of 20% or higher, it may be reasonable to add ezetimibe to
maximally tolerated statin therapy to reduce LDL-C levels by
50% or more
 Diabetes Mellitus in Adults

 In adults older than 75 years of age with diabetes

mellitus and who are already on statin therapy, it is reasonable to
continue statin therapy.

 In adults older than 75 years with diabetes mellitus, it

may be reasonable to initiate statin therapy after a clinician–
patient discussion of potential benefits and risks.

 In adults 20 to 39 years of age with diabetes mellitus that

is either multiple risk factor or risk enhancer may be reasonable
to initiate statin
 Pharmacologic recommendations
Therapy recommendations are divided into patient
management groups:
a. Secondary ASCVD prevention

b. Severe hypercholesterolemia (LDL-C ≥190 mg/dL)

c. Diabetes mellitus (DM)

d. Primary prevention
Risk-enhancing factors (e.g. CKD , metabolic syndrome, elevated CRP,
premature ACVD)
 Primary Prevention
Primary Prevention Adults 40 to 75 Years of Age With LDL-C Levels 70 to 189 mg/dL
(1.7 to 4.8 mmol/L)

 In adults at intermediate-risk, statin therapy reduces risk of

ASCVD, and in the context of a risk discussion, if a decision is
made for statin therapy, a moderate-intensity statin should be
recommended.

 In intermediate-risk patients, LDL-C levels should be reduced

by 30% or more, and for optimal ASCVD risk reduction,
especially in high-risk patients, levels should be reduced by
50% or more
 Primary Prevention
Primary Prevention Adults 40 to 75 Years of Age With LDL-C Levels 70 to 189 mg/dL
(1.7 to 4.8 mmol/L)

 In intermediate-risk adults who would benefit from more

aggressive LDL-C lowering and in whom high-intensity statins
are advisable but not acceptable or tolerated, it may be
reasonable to add a non-statin drug (e.g. ezetimibe) or BAS to
a moderate-intensity statin.

 In patients at borderline risk, in risk discussion, the presence

of risk-enhancing factors (e.g. CKD , metabolic syndrome,
elevated CRP, premature ACVD) may justify initiation of
moderate intensity statin therapy
 Primary Prevention
Primary Prevention Adults 40 to 75 Years of Age With LDL-C Levels 70 to 189 mg/dL
(1.7 to 4.8 mmol/L)

 Clinicians and patients should engage in a risk discussion that

considers risk factors, adherence to healthy lifestyle, the
potential for ASCVD risk-reduction benefits, and the potential
for adverse effects and drug–drug interactions, as well as
patient preferences, for an individualized treatment decision

 In intermediate-risk adults, risk-enhancing factors favor

initiation or intensification of statin therapy

 In intermediate-risk or selected borderline-risk adults, if the

decision about statin use remains uncertain, it is reasonable
to use a CAC score in the decision to withhold, postpone or
initiate statin therapy
Coronary Artery Calcium (CAC) Scoring

Coronary artery calcium (CAC) scoring, also called a

coronary calcium scan, is a test that measures the
amount of calcium in the walls of the heart’s
arteries.

A way to estimate someone’s risk of developing heart

disease or having a heart attack or stroke.
Coronary Artery Calcium (CAC) Scoring

Score = 0: consider no statin (unless DM, family history

of premature coronary heart disease, or cigarette
smoking present) reassess in 5 to 10 years

Score = 1-99: favors statin if age ≥55

Score ≥100 or ≥75th percentile: favors statin

Low Dose Aspirin
 Low Dose Aspirin

Established risk factors for bleeding include:

• Diabetes
• Prior bleeding event
• Family history of cardiovascular disease
• Cancer
• Concomitant use of anticoagulant or other antiplatelet medications
• Current or past smoking history ( tobacco have been suspected to
cause changes in the arterial wall leading to instability of blood vessels)
• Chronic liver disease, chronic pancreatitis or alcohol- related
conditions
• Helicobacter pylori infection or history of peptic ulcer disease
M.M. is a 63-year-old white woman who just finished 6 months of
diet and exercise for dyslipidemia. She has a history of
hypertension, and asthma. She smokes one pack of cigarettes and
drinks three beers per day. Her mother had HTN and suffered an
MI at age 42 years. Her father had HTN and DM. Her medications
are albuterol metered dose inhaler, lisinopril and calcium
carbonate antacids. Her vital signs include BP 134/84 mm Hg and
HR 75 beats/minute. Her laboratory results are as follows: HDL-C
38 mg/dL, LDL-C 220 mg/dL, TG 220 mg/dL, TC 209 mg/dL, and
ASCVD = 20%. What is the most appropriate next step for M.M.?
A. Initiate a low-intensity statin
B. Initiate a moderate-intensity statin
C. Initiate a high-intensity statin
D. Initiate a high-intensity statin plus ezetimibe
If after treatment LDL-C= 150

high-intensity statin plus ezetimibe

If after treatment LDL-C=130

high-intensity statin plus ezetimibe + PCSK9 I

Does this patient is candidate for aspirin ? Justify

Yes , high risk ASCVD

 Patients age >75 years

i. Reasonable to initiate a moderate-intensity statin or

continue a moderate- or high-intensity statin if benefits
outweigh risks

ii. Reasonable to discontinue statin therapy if patients

have functional decline, multimorbidity, frailty, or reduced
life expectancy limits potential benefits
 Hypertriglyceridemia

i. Primary goal is to prevent pancreatitis

ii. Evaluate for secondary causes
 Hypertriglyceridemia

Moderate hypertriglyceridemia (triglycerides [TG]

175-499 mg/dL)
(a) Address and treat lifestyle factors, comorbidities,
and medications which increase TGs

(b) If persistently elevated and ASCVD risk ≥7.5%,

consider initiation or intensification of statin therapy
 Hypertriglyceridemia

Severe hypertriglyceridemia (TG ≥ 500 mg/dL)

(a) If persistently elevated and ASCVD risk ≥7.5%,
consider initiation or intensification of statin
therapy
(b) Reasonable to initiate fibrate therapy to prevent
acute pancreatitis, especially if fasting TG ≥ 1000
mg/dL
3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase
inhibitors (statins)
General approach to initiating statin therapy
a. Fasting lipid panel
i. If baseline LDL-C is higher than 190 mg/dL, evaluate for
secondary causes. If primary, screen for familial
hypercholesterolemia.
b. Alanine aminotransferase (ALT)
i. Evaluate patients with unexplained ALT more than 3x upper
limit of normal
c. Hemoglobin A1C
d. Creatine kinase
e. Evaluate for secondary causes or conditions that may affect statin
safety
3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase
inhibitors (statins)
Main adverse effects and monitoring
a. Myopathy (can check creatine kinase [CK]
b. Elevated liver enzymes
i. Obtain LFTs at baseline in all patients
ii. Perform repeated LFTs only when clinically indicated.
iii. Monitor for symptoms of hepatic injury.
c. A clinically relevant concern with statin therapy is a significantly increased risk of new-
onset diabetes in patients on statin therapy

Absolute contraindications
a. Active liver disease, unexplained persistent elevations in hepatic transaminases
b. Pregnancy
c. Nursing mothers
d. Certain medications (e.g. Azole antifungal and erythromycin and clarithromycin with
simvastatin)

Select drug interactions

a. Fibrates: Increased risk of myopathy and rhabdomyolysis when coadministered with
statins. Risk is greater with gemfibrozil than with fenofibrate.
b. Niacin: Doses greater than 1 g/day increase the risk of myopathy and rhabdomyolysis
when used concomitantly with statins; risk is lower than with fibrates; statins and niacin are
commonly used together; monitor for muscle pain.
 Ezetimibe
Ezetimibe is a potent and selective inhibitor of
cholesterol absorption that has been shown to
reduce the overall delivery of cholesterol to the
liver, thereby promoting the synthesis of LDL
receptors, with a subsequent reduction of serum
LDL-C.

S.E: Diarrhea, upper respiratory tract symptoms

(stuffy nose, sinus pain, sore throat); no
monitoring necessary
 PCSK9 Inhibitors
Evolocumab, Alirocumab

PCSK9 is an enzyme that is encoded to the PCSK9

gene It binds to the LDL receptor in the liver ,
When it binds to the LDLR, the receptor is broken
down and can no longer remove LDL-C from the
blood
S.E: Injection-site reactions,
respiratory infections
 Fibrates
fibrates stimulate LDL receptor-dependent clearance
mechanisms and reduce the amount of LDL available for
oxidation.

S.E: Dyspepsia, gallstones, myopathy, increased hepatic

transaminases. Monitor LFTs every 3 months during first
year and then periodically.

Contraindications: Severe renal or hepatic disease, pre-

existing gallbladder disease
Bile acid sequestrants (cholestyramine, colestipol, colesevelam)

 May increase TG concentrations.

 Reduce major coronary events.

 Adverse effects: GI distress, constipation

 Decreased absorption of many drugs including: warfarin,

amiodarone, levothyroxine, ezetimibe, digoxin, and thiazides;
administer drugs 1–2 hours before or 4 hours after bile acid
sequestrant

 Contraindications: Complete biliary obstruction, raised TG

concentrations (especially greater than 400 mg/dL)
Niacin According to the latest guidelines, there are no clear indications for
routine niacin use for reduction of LDL-C.

Adverse effects and monitoring: Flushing, hyperglycemia,

hyperuricemia, myopathy, upper GI distress, increased hepatic
transaminases; monitor LFTs at baseline, every 6–12 weeks for
first year and then yearly

Flushing can be minimized by taking aspirin or an NSAID 30–60 minutes

before niacin, taking at bedtime with food, using slow titration, and avoiding
hot beverages, spicy foods, and hot showers around the time of
administration.

Contraindications: liver disease and active peptic ulcer disease.

Caution in patients predisposed to gout
 Omega-3 fatty acids

Inhibit hepatic triglyceride (TG) synthesis, such as through

the inhibition of TG synthetic enzymes

S.E: Arthralgia, GI effects (e.g., burping, taste perversion,

dyspepsia); and
at more than 3 g/day, bleeding (because of inhibition of
platelet aggregation)
 Faculty of
Pharmacy