Successfully reported this slideshow.
We use your LinkedIn profile and activity data to personalize ads and to show you more relevant ads. You can change your ad preferences anytime.

Role of Statin in Secondary Prevention of ACS


Published on

dr. Dasdo Antonius Sinaga, SpJP, FIHA. 3rd Pekanbaru Cardiology Update, August 25th 2013. Pangeran Hotel Pekanbaru. Learn more at

Published in: Health & Medicine
  • Be the first to comment

Role of Statin in Secondary Prevention of ACS

  1. 1. Dasdo A Sinaga Cardiologist
  2. 2. SECONDARY PREVENTION PRIMARY PREVENTION: To prevent cardiovascular event in patients without evidence of cardiovascular disease RISK FACTORS SECONDARY PREVENTION To prevent further events in patients with clinical evidence of cardiovascular disease RISK FACTORS
  3. 3. Guidelines target modifiable risk factors BEHAVIOR Poor diet Physical inactivity Cigarette smoking Excessive alcohol NONMODIFIABLE RISK FACTORS Age Sex Genetic predisposition MODIFIABLE RISK FACTORS Elevated LDL-C Hypertension Reduced HDL-C Diabetes Obesity Smoking Socio-economic, cultural and environmental conditions and modernization, mechanization, urbanization, globalization Adapted from Shao R. Presentation at the Global Forum on NCD Prevention and Control, 9-12 November 2003, Rio de Janeiro. EXTERNAL FACTORS CV EVENTS Coronary heart disease Myocardial infarction Congestive heart failure Stroke Peripheral arterial disease
  4. 4. RISK FACTORS Age, Gender Family History Smoking Habit Dyslipidemia Hypertension Diabetes Mellitus CARDIOVASCULAR EVENT ACUTE CORONARY SYNDOME: Unstable Angina Pectoris Acute NSTEMI STEMI STROKE RE-INFARCTION CARDIOVASCULAR DEATH STROKE HEART FAILURE Primary Prevention Secondary Prevention
  5. 5. Patients with UA/NSTEMI and STEMI require secondary prevention for CAD at discharge. The management of the patient is detailed in the ACC/AHA/ ACP Guidelines for the Management of Patients With Chronic Stable Angina, ACC/AHA Guidelines for the Management of Patients With ST- Elevation MI Secondary Prevention Long-Term Medical Therapy and Secondary Prevention
  6. 6. AFTER DISCHARGE LONG TERM Medical Therapy HOW LONG? Non Medical Management: Diet Physical Activity Complimentary Treatment ??
  7. 7. SECONDARY PREVENTION Smoking Cessation Blood Pressure Control Lipid Management Physical Activity Weight Management Diabetes Management Antiplatelet Agent Renin-Angiotensin Aldosterone Inhibitor Beta-Blockers Influenza Vaccination
  8. 8. LIPID MANAGEMENT Dietary therapy that is low in saturated fat and cholesterol (< 7% of total calories as saturated fat and < 200 mg/d cholesterol) started on discharge after recovery from ACS. Increased consumption of the following: omega–3 fatty acids, fruits, vegetables, soluble (viscous) fiber, and whole grains. Calorie intake should be balanced with energy output to achieve and maintain a healthy weight.
  9. 9. Lipid Profile Assessment A lipid profile should be obtained from past records, but if not available, it should be performed in all patients with Acute Coronary Syndrome Preferably after they have fasted Within 24 hours of admission.
  11. 11. Non-HDL Cholesterol = all bad Cholesterol = Total Chol - HDL Total Cholesterol LDL Cholesterol Trigliseride HDL Cholesterol 1. LDL 100 mg/dl 70 mg/dl 2. NON- HDL 130 mg/dl 100 mg/dl 3. Trigliseride > 500 Pankreatitis 3. HDL Cholesterol
  12. 12. Kolesterol Total 230 LDL 150 HDL 30 Trigliserida 240 Kolesterol Total 210 LDL 120 HDL 60 Trigliserida 148
  13. 13. *Therapeutic option 70 mg/dL =1.8 mmol/L; 100 mg/dL = 2.6 mmol/L; 130 mg/dL = 3.4 mmol/L; 160 mg/dL = 4.1 mmol/L LDL-Clevel 70 - 130 - 100 - 160 - Lower Risk < 2 risk factors High Risk CHD or CHD risk equivalents (10-yr risk >20%) Goal 160 mg/dL Goal 130 mg/dL 40 - Goal 70 mg/dL* Moderate Risk ≥ 2 risk factors (10-yr risk <10%) Goal 100 mg/dL* Grundy SM et al. Circulation 2004;110:227-239. Proposed LDL-C goals NCEP ATP III Guidelines: LDL-C Goals (Update 2004) Very high risk CVD + •Multiple major risk factors (Diabetes) •Smoking •Metab Synd •ACS
  14. 14. LDL-Cholesterol >= 100 mg/dl prescribed drug therapy on hospital discharge, preference: statins. LDL-C < 100 mg/dL or unknown prescribed statin therapy on hospital discharge. Non HDL-C < 130 mg/dL HDL-C level < 40 mg/dL should receive special emphasis on nonpharmacological therapy (eg, exercise, weight loss, and smoking cessation) to increase HDL-C.
  15. 15. Elevated LDL-C (>= 100 mg per dL), further therapy to achieve an LDL-C < 100 mg/dL. Further titration to < 70 mg/dL is reasonable. If triglycerides are greater than or equal to 500 mg/dL, therapeutic options to prevent pancreatitis are fibrate or niacin before LDL-lowering therapy is recommended. It is also recommended that LDL-C be treated to goal after triglyceride-lowering therapy.
  16. 16. EARLY SECONDARY trials before the use of statin therapy VS STATIN therapy significant reductions of 25% in nonfatal Myocardial Infarctions and 14% in fatal Myocardial Infarction Subsequently, a growing body of evidence, mainly from large randomized clinical trials of statin therapy, has firmly established the desirability of lowering atherogenic serum lipids in patients who have recovered from a STEMI.
  17. 17. Hydroxymethyl glutaryl-coenzyme A reductase inhibitors (HMG CoA Reductase Inhibitor / statins), in the absence of contraindications, regardless of baseline LDL-C and diet modification, should be given to post-ACS patients, including post- revascularization patients. Lipid-lowering medications should be initiated before discharge. STATIN
  18. 18. 26 Statin Mechanism Of Action Statin Liver Peripheral cell Vessel LDL receptor HMG-CoA Mevalonic acid Cholesterol HMG-CoA reductase
  19. 19. Atherosclerosis: A Progressive Disease CRP=C-reactive protein; LDL-C=low-density lipoprotein cholesterol. Libby P. Circulation. 2001;104:365-372; Ross R. N Engl J Med. 1999;340:115-126. Monocyte LDL-C Adhesion molecule Macrophage Foam cell Oxidized LDL-C Plaque rupture Smooth muscle cells CRP Plaque instability and thrombusOxidationInflammation Endothelial dysfunction
  20. 20. 28 Statin’s Pleiotropic Effects in Atherosclerotic Lesion Inhibitory actionInhibitory actionInhibitory actionInhibitory action on thrombosison thrombosison thrombosison thrombosis formationformationformationformation Plaque stabilizationPlaque stabilizationPlaque stabilizationPlaque stabilization LDLLDLLDLLDL MonocyteMonocyteMonocyteMonocyte PlateletPlateletPlateletPlatelet Endothelial cellEndothelial cellEndothelial cellEndothelial cell Inhibitory action onInhibitory action onInhibitory action onInhibitory action on monocyte adhesionmonocyte adhesionmonocyte adhesionmonocyte adhesion Oxidized LDLOxidized LDLOxidized LDLOxidized LDL Improvement ofImprovement ofImprovement ofImprovement of endothelial functionsendothelial functionsendothelial functionsendothelial functions Inhibitory action on migration andInhibitory action on migration andInhibitory action on migration andInhibitory action on migration and proliferation of smooth muscle cellsproliferation of smooth muscle cellsproliferation of smooth muscle cellsproliferation of smooth muscle cells MacrophageMacrophageMacrophageMacrophage Inhibitory action onInhibitory action onInhibitory action onInhibitory action on change from Mchange from Mchange from Mchange from MΦ intointointointo foam cellsfoam cellsfoam cellsfoam cells
  21. 21. Pleitropic Effects of Statins Statins pleitropic effects are dissociated from their hypolipidemic effects. These effects include: Wassmann S, et al Endothelium. 2003;10:23-33. Endothelial function NO bioactivity Endothelin Endothelial progenitor cells Macrophages Inflammation Immunomodulation Immune injury Coagulation Platelet activation Thrombogenicity Proliferation LDL-C HDL-C Triglycerides (TG) Plaque progression MMPs Collagen Plaque stability AT1 receptor Antioxidant effect Free radicals Early intensive treatment with a statin is both safe and effective in the acute phase after MI or UA ( PROVE IT, MIRACLE, A to Z )
  22. 22. 30
  23. 23. 31 Cyclopropyl group Hydrophilic areas Hydrophobic areas Hydrophobic areas Hydrophobic areas Mode of Action pitavastatin simvastatin atorvastatin IC50 (nM) 5.8 17.1 32.9 [ratio] [1] [2.9] [5.7] J. Atheroscler. Thromb 7(3): 138, 2000 Figure 5 - Pitavastatin in the complex with active site of human HMG-CoA Reductase ( Adapted from Yamazaki et al )
  24. 24. Solubility (log P) CYP Metabolism (in human) Excreted asActive Metabolite T1/2 (hr) BA (%) Excretion into urine (%) Drugs Pravastatin Water- soluble (-0.47) Negligible Unchanged– 18 20 1-2 Fluvastatin Lipid- soluble (1.73) CYP2C9 MetaboliteNo 10 - 35 <6 1.2 Atorvastatin Lipid- soluble (1.53) CYP3A4 No DataYes 12 2 14 PitavastatinPitavastatin Lipid- soluble (1.49) Unchanged– 60* < 2 11Negligible Simvastatin Lipid- soluble (4.40) CYP3A4 Yes < 5 13 1-2Metabolite NotMetabolized byCYP Metabolizedby CYP * Estimated from first pass metabolism model Rosuvastatin Water- soluble (-0.33) Slightly metabolized CYP2C9, 2C19 Mainly Unchanged– 20 10 19 Medical Consultation & New Remedies 2003; 40(5): 351 J Clin Pharmacol.2002; 42(8): 835, J Clin Pharmacol.2003;43(9):1015 What STATIN ?
  25. 25. Source : Saito Y, Teramoto T, Yamada N, et al. Clinical efficacy of NK-104 (Pitavastatin), a new synthetic HMG-CoA reductase inhibitor, in the dose finding, double –blind, three-group comparative study. J Clin Ther Med. 2001; 17: 829-55. Japanese. Mean % Change of Lipid Profiles with Pitavastatin ( LDL-C lowering effect until 47% within 12 weeks ) ( Dose Finding Study )
  26. 26. Over 12 weeks Pitavastatin was non-inferior to Atorvastatin in reducing LDL-C and increasing HDL-C Budinsky, Clin.Lipidol, 4/3,291-302, 2009
  27. 27. Pitavastatin was non-inferior compared to simvastatin in reducing LDL-C and increasing HDL-C Ose L et al. 2009;25(11):2755-64
  28. 28. Change in LDL-C 4,530 3,499 3,550 4,228 4,987 5,115 5,339 5,464 162.4 ±34.6 108.5 ±27.2 0 3 months 6 months 1 year 2 years 3 years 4 years 5 years -30.5% Mean±S.D. p<0.001 (repeated measures ANOVA) (mg/dL) 80 100 120 140 160 180 200 0 60 No. of patients LDL-C Teramoto T, et al. Jpn Pharmacol Ther 2011;39:789–803
  29. 29. Time Course of HDL-C Level (Subgroup with baseline HDL-C <40 mg/dL) Percent change 14.0±±±±20.1 16.1±±±±21.5 20.3±±±±22.0 24.9±±±±27.5 (mg/dL) 30 35 40 45 50 55 0 12 28 52 104 0 Mean±S.D. (n=86) p<0.001 by ANOVA and linear regression model (weeks) 35.4 ±3.2 40.4 ±7.6 41.0 ±7.5 42.5 ±7.8 44.1 ±9.3 HDL-C target* *Recommended by JAS Guideline 2007 Teramoto T et al. J Atheroscler Thromb. 2009;16(5):654
  30. 30. Impact of Statin Therapy on Plaque Characteristics To evaluate the effect of statin treatment on coronary Plaque composition and Morphology by optical coherence tomography (OCT), grayscale and integrated backscatter (IB) intravascular ultrasound (IVUS) imaging The result of this study was published in JACC in 2012 Hattori K et al. J Am Coll Cardiol 2012; 5: 169-177
  31. 31. Inclusion Criteria : Stable Angina Patients who have been undergoing elective PCI to evaluate the effect of statin therapy on nontarget lession Exclusion Criteria : Patients already established on lipid-lowering therapy and those with contraindications to repeat coronary angiography and intra-coronary imaging Study Design : non-randomized, case-control study Methods : 42 patients with stable angina undergoing elective PCI ( 26 received pitavastatin 4 mg/day and 16 who declined any form of lipid-lowering pharmacotherapy received dietary intervention alone Post PCI : Serial OCT, Grayscale and IB- IVUS 9 months Serial OCT, Grayscale and IB-IVUS Pitavastatin 4mg/dayPitavastatin 4mg/day Diet Only Non- RandomizedStable Angina Protocol Non- Randomized Case control study Hattori K et al. J Am Coll Cardiol 2012; 5: 169-177
  32. 32. Result of Pitavastatin Group
  33. 33. Result of Dietary Group
  34. 34. Treatment with Pitavastatin in patients with stable angina post PCI induces Significant plaque regression and, By decreasing plaque lipid content and Increasing plaque fibrous cap thickness, and induces plaque stabilization Conclusion of the research Hattori K et al. J Am Coll Cardiol 2012; 5: 169-177
  35. 35. % Change in Plaque Volume ALL (n=252) Atorvastatin 20mg (n=127) Pitavastatin 4mg (n=125) -30 -20 -10 0 -17.5% n.s. *** *** *** :p<0.001*** Hiro T et al. J Am Coll Cardiol 2009 MonocyteLDL-C Adhesion molecule Macrophage Foam cell Oxidized LDL-C Plaque rupture Smooth muscle cells CRP
  36. 36. SUMMARY Lipid Management is crucial as a part of secondary prevention in patients with Acute Coronary Syndrome Lifestyle Modification and Medical Therapy Early Intensive Statin in all ACS patients, REGARDLESS of the cholesterol levels Beyond lowering cholesterol level, PLEIOTROPIC effect of statin is beneficial for all CAD patients. Tailored targeted cholesterol level is encouraged In high risk patients, LDL < 70 mg/dl should be reached. Pitavastatin proven as a potent statin in reducing LDL and enhancing HDL-cholesterol level.
  37. 37. THANK YOU