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Statin untuk Pencegahan Primer Komplikasi Kardiovaskular pada Pasien DM tipe 2 dengan Profil Lipid yang baik: Laporan Berbasis Bukti
Alvin Nursalim,* Pradana Soewondo,** Indah S. Widyahening***
*Fakultas Kedokteran Universitas Indonesia, Jakarta **Departemen Ilmu Penyakit Dalam Rumah Sakit Cipto Mangunkusuno, Jakarta ***Departmen Ilmu Kedokteran Komunitas Fakultas Kedokteran Universitas Indonesia, Jakarta

Abstrak: Penyakit jantung diabetik merupakan penyebab mortalitas tertinggi pada penyandang DM. Faktor risiko yang turut berperan dalam terjadinya komplikasi kardiovaskular pada penyandang DM adalah dislipidemia. Banyak studi menunjukkan efektivitas statin dalam memperbaiki profil lipid penyandang DM tipe 2 dengan dislipidemia yang pada akhirnya menyebabkan penurunan komplikasi kardiovaskular. Laporan ini dibuat untuk mengetahui apakah statin efektif sebagai pencegahan komplikasi kardiovaskular pada penyandang DM dengan profil lipid yang normal. Pencarian terstruktur dilakukan dengan menggunakan Pubmed, Medline dan Google. Setelah dilakukan penapisan judul dan abstrak dengan kriteria inklusi dan eksklusi, sebelas studi ditemukan, tetapi hanya tiga studi yang digunakan penulis. Ketiga studi ditelaah dengan menggunakan kriteria yang mencakup validity, importance, dan applicability untuk menentukan derajat kegunaan dalam studi ini. Ketiga studi tersebut menunjukkan penurunan komplikasi dan mortalitas kardiovaskular pada kelompok terapi statin. Hal ini terlihat dari relative risk reduction yang berkisar antara 18-37,5%. Absolute risk reduction berkisar antara 1,9-3% dan number needed to treat yang berkisar antara 33-53. Selain penurunan angka komplikasi kardiovaskular, ketiga studi itu juga melaporkan terdapatnya penurunan komplikasi serebrovaskular pada pasien yang diberikan terapi statin. Pemberian statin merupakan terapi yang efektif dalam menurunkan komplikasi kardiovaskular pada pasien DM tipe 2 dengan profil lipid normal. J Indon Med Assoc. 2011;61:363-7. Kata Kunci: Diabetes mellitus tipe 2, dislipidemia, statin, profil lipid normal, kardiovaskular

J Indon Med Assoc, Volum: 61, Nomor: 9, September 2011

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dyslipidemia. This report aims to identify whether statin is effective in preventing cardiovascular complication among diabetic patients with normal lipid profile.3 As the number of DM patients increased worldwide. normal lipid profile. there will be 380 millions patients with DM in 2025. Pradana Soewondo**. It is due to the premature atherosclerosis process.7%. Jakarta Abstract: One of the most fatal complications in diabetic patients is diabetic heart disease.6 A normal lipid profile will reduce the occurrence of cardiovascular complication eventually. Introduction Diabetes mellitus (DM) is a metabolic disorder characterized by hyperglycemia.Statin untuk Pencegahan Primer Komplikasi Kardiovaskular pada Pasien DM tipe 2 Statin Administration for Primary Prevention of Cardiovascular Complication Among Type 2 Diabetic Patients with Good Lipid Profile: Evidence Based Report Alvin Nursalim*. J Indon Med Assoc. 1 The prevalence of DM increased in the last two decades.All three studies showed the reduction in cardiovascular complication and mortality related to cardiovascular. All selected studies were critically appraised for its validity. Dyslipidemia becomes one of many risk factors that contribute to the occurrence of cardiovascular complication among diabetic patients. DM is commonly accompanied by others metabolic disorders. The administration of statin is effective in reducing the risk of cardiovascular complication among type 2 diabetic patients with normal lipid profile. Nomor: 9.” “statin. Some studies showed the effectiveness of statin in improving lipid profile among type 2 diabetic patients with dyslipidemia.® and Google. ® on April 2nd and 4th 2011.5 Many studies show the effectiveness of statin in improving lipid profile among type 2 diabetic patients with dyslipidemia. kidney and blood vessels in long term. Compared with people who do not have diabetes. but only three studies were used.1. importance and applicability. A search was conducted on PubMed and Google. J Indon Med Assoc. Clinical Question Is statin administration effective as primary prevention for cardiovascular complication among type 2 diabetic patients with normal lipid profile? Method The search was conducted on PubMed. which finally reduce the occurrence of cardiovascular complication.4 Diabetic heart disease refers to heart disease that happens among diabetic patients due to metabolic factors interaction. Eleven original articles were found.5%. The absolute risk reduction ranged from 1. statin. the number of DM patients with complication would increase eventually. Volum: 61. The number of DM cases increased from 30 millions cases in 1985 to 177 millions cases in 2000. diabetic patients have twice to four times the risk of developing coronary heart disease. Diabetic heart disease is the number one cause of mortality among DM patients. Diabetes mellitus causes a wide variety of chronic complications on so many organs such as: eyes. Diabetic patients de- velop coronary heart disease at younger age compared to those who do not have diabetes. Keywords: Type 2 Diabetes mellitus. Faculty of Medicine Universitas Indonesia. Widyahening*** *Faculty of Medicine Universitas Indonesia.” “diabetes” and “cardiovascular” along with its synonyms and related terms (Table 1).2 According to International Diabetes Federation. The prevalence of Type 2 DM in Indonesia is 5. Jakarta **Department of Internal Medicine Faculty of Medicine Universitas Indonesia Cipto Mangunkusumo Hospital. The relative risk reduction ranged from 18-37. Jakarta ***Department of Community Medicine.61:363-7.1. statin therapy was also proven to decrease the occurrence of cerebrovascular complication among type 2 diabetic patients. September 2011 364 . 2011. After the selection of title and abstract was done using inclusion and exclusion criteria. Indah S. using the keywords “adult.9%-3% and number needed to treat ranged from 33-53. Beside the reduction in cardiovascular complication. cardiovascular disease. This report is made to identify whether statin administration is effective as primary prevention of cardiovascular complication among type 2 diabetic patients with normal lipid profile.

6%.Statin untuk Pencegahan Primer Komplikasi Kardiovaskular pada Pasien DM tipe 2 Table 1.9 -3% and the NNT ranged from 33-55. These three articles were appraised and considered to have a good validity and relevance.5%. The mortality rate reduction in 365 Pubmed (adult) AND diabetes) AND statin) AND (2 April 2011) (cardiovascular OR vascular event) Google Adult statin diabetesCardiovascular (4 April 2011) Search strategy. et al8 also found a significant reduction in the occurence of cardiovascular complication.6%) in the placebo group.5%.001). Relative Risk Reduction (RRR) was 34. Beside cardiovascular complication. out of which only three full-text articles were availJ Indon Med Assoc. obtained after searching. Colhoun et al7. Medline and Google (Conducted on April 2nd and 4th 2011) Database Search terms Results 55 4 able. statin administration is proven to be effective and safe. The result of this study was the administration of pravastatin reduced mortality rate due to coronary heart disease. 37. RRR was 37. selection and filtration method.10 Result From the selection and filtration. Volum: 61. Experimental Event Rate (EER) was 3. According to this study. Beside the reduction of cardiovascular complication. Discussion Colhoun HM et al7 conducted a study to evaluate whether the administration of 10 mg of atorvastatin is significantly useful in reducing the occurence of primary cardiovascular complication among diabetic patients with good lipid profile. and NNT was 33. Collins R.5% and 46% respectively. Absolute Risk Reduction (ARR) was 1. Colhoun et al7. Collins et al8 and Goldberg B et al9 showed that statin administration significantly reduce the occurence of cardiovascular risk as much as 37%. The patients involved in this study have good-borderline lipid profile. The ARRs in these three studies ranged from 1. The result of this study is that the administration of 10 mg of atorvastatin everyday reduce the risk of cardiovascular complication as much as 37% with the Control Event Rate (CER) was 5. Search date: April 4. Collins et al8 and Goldber B et al9 also provided the comparison of mortality rate among the two groups. ARR was 3%. University of Oxford for therapy study (Table 2). Colhoun et al7 also showed a 48% reduction in the occurence of stroke. This study involved 20 536 patients. results and the inclusion and exclusion criteria are shown in a flowchart (Figure 1). Goldberg et al9 conducted a study about the administration of pravastatin in 586 diabetic patients. Statin administration is considered safe due to the minimal side effect occured during this study. critical appraisal was done using several aspects based on Center of Evidence-based Medicine.5%) who finally got cardiovascular complication compared with 574 patients (5. Collins et al8 and Golgberg B et al9 showed similar result that the administration of statin in diabetic patients with good clinical profile will eventually lead to reduction of cardiovascular complication. eleven articles were obtained. Nomor: 9. The NNT from these three journals can still be considered beneficial since preventive meassure that produced small effects in large numbers of patients will have high NNT.5%. In the simvastatin group there were 357 patients (3. The RRR was 18%. aged between 40-80 years old with good to borderline lipid profile. Three articles. Search Strategy Used in PubMed.9% and Number Needed to Treat (NNT) was 53 (p=0. 2011 Figure 1. reported the use of statin for good to borderline lipid profile. Out of 2838 patients participated in this study only a small proportion of patients were diagnosed to have rhabdomyolisis (61 patients in statin group and 72 patients in placebo group). September 2011 .1% and NNT was 47. Flow Chart of Search Strategy After the selection. ARR was 2.

A 46 years old man was diagnosed 366 with type 2 diabetes mellitus. New York: McGraw-Hill Co.. There were no abnormality found on the X-ray and electrocardiography examination. 2003. Belgia. Beside the reduction of cardiovascular complication. Heart Protection Study Collaborative Group. Powers AC. so risk factors stratification could be put into consideration when presented with a diabetic patient with good lipid profile. 5.12(2):80-3.6%) in the placebo group. Unfortunately.001) B: There are 357 (3. these studies also concluded that statin therapy reduce the mortality rate and the occurence of cerebrovascular complication. This patient had been smoking for more than 20 years and rarely had excercise. Jakarta. Longo D. 6. Although the side effects observed in these study is minimal. Sleight P. 2008. Available from: URL:HYPERLINK http:// emedicine. 3 rd edition. LDL and HDL). the doctor also prescribed atorvastatin 10 mg to be consumed once daily. 2004.Statin untuk Pencegahan Primer Komplikasi Kardiovaskular pada Pasien DM tipe 2 Table 2. Emedicine [cited 2011 April 4]. compared to 574 (5. et al8 Goldberg RB et al9 + + + 2838 20536 586 + + + + + + + + + + + + ? + ? + + + Determinant Study design Blinding Domain + + + + + + A B C 1B 1B 1B Legend: + stated clearly in the article . Hauser S. Konsensus pengelolaan dan pencegahan diabetes mellitus tipe 2 di Indonesia. Volum: 61. Collins R. the patient was in a good condition and there was no diabetic complication observed. tryglyceride. Harrison’s Principles of Internal Medicine. 2166-8. Diabetes spectrum. Hitman GA. Betteridge DJ. type 2. 4. Parish S. The laboratory findings were all within normal range. C. Critical Appraisal of the 3 usefull articles based on criterias by Centre of Evidence Medicine University of Oxford 10 Validity Articles Similarity treatment and control Number of patients Relevance Comparable treatment Result Intention to treat Meassurement of outcome Levels of evidence* Randomization Colhoun HM et al7 Collins R. Durrington PN. Peto R. Neil HAW. Diabetes Atlas. including lipid profile (total cholesterol. The statin prescription for this patient is an effective preventive meassure for cardiovascular complications. the most common side effect of statin therapy. Lancet. Jameson JL. 8. According to statin characteristics and its efficacy. Nomor: 9.medscape. Braunwald E. et al. 17th edition. follow-up is recommended for all patients receiving statin therapy. Diabetes and coronary heart disease.05) the statin group is mainly due to the reduction of cardiovascular complication. Isley W L. 2006. Rhabdyomyolisis. Colhoun HM. Fauci AS. Jakarta. Conclusion All three studies gave the same recommendation that the administration of statin is a safe and effective way to reduce cardiovascular complication among type 2 diabetic patients with good lipid profile. Effects of cholesterol-lowering with simvastatin on stroke and other major vascular events in 20536 people with cerebrovascular disease or other high-risk 2. statin can be used as a preventive measure of cardiovascular complication among diabetic patients. can be identified by creatine-kinase examination. International Diabetes Federation. Recommendation for Clinical Use These report can be translated into clinical practise with the following example. References 1. 3. According to physical examination. editors. p: 0. 1999.not being done ? not stated clearly * Levels of evidence based on The Oxford Centre of Evidence-based Medicine A: The result of this study is that the administration of 10 mg atorvastatin everyday reduce the occurence of cardiovascular complication as much as 37% on those patients without previous history of cardiovascular complication (p=0.364:685-96. J Indon Med Assoc.com/article/117853-overview Meng HT. September 2011 . In: Kasper DL. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. As stated above.5%) patients had myocardial infarction in the simvastatin group. p. Armitage J. 7. Diabetes Mellitus. Diabetes Mellitus. PERKENI. Livingstone SJ. 2008 Ligaray KPL. The administration of Parastatin on DM patients is related with cardiovascular complication risk reduction (Relative Risk: 25%. there was no definite lipid profile range as to begin statin therapy. Some statins are affordable and can be purchased with prescription in any pharmacy. Beside the regular prescriptions of oral diabetic medication. cardiovascular complication is the leading cause of mortality among diabetic patients. Statin is a widely known drug and well distributed acrossed Indonesia. Laporan riset kesehatan dasar Indonesia tahun 2007. Departemen Kesehatan Republik Indonesia. It is also crucial to encourage a healthy lifestyle modification to all diabetic patients before implementing any medication.

Lancet. Centre for Evidence Based Medicine. Goldberg RB. 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. [cited 2011 April 4]. Oxford Centre for Evidence-based Medicine. Howard BV. J Indon Med Assoc.363:757-67. 10. 1998. net/index. 2004. Mellies MJ. September 2011 367 .2513-19. Circulation .98. Howard WJ. CEBM. Moye LA.aspx?o=5513 FS 9. Sacks FM.Statin untuk Pencegahan Primer Komplikasi Kardiovaskular pada Pasien DM tipe 2 conditions. Volum: 61.Level of Evidence.cebm. et al. Available from: URL:HYPERLYNK http://www. Nomor: 9.