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Atorwin rtd 2014 dr sukartono
- Studies have shown that lowering LDL cholesterol through statin therapy such as atorvastatin provides significant cardiovascular benefits in both primary and secondary prevention. Atorvastatin in particular has been shown in clinical trials to reduce cardiovascular events and mortality when used for acute coronary syndromes, stable coronary heart disease, and among those at high risk of cardiovascular disease. Atorvastatin may be a good choice of statin due to its proven efficacy in improving cardiovascular outcomes.
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Atorwin rtd 2014 dr sukartono
- 1. Dyslipidemia Management with Better CVD Risk Prevention Dr Sukartono Toposubroto SpPD RSI Pekajangan Pekalongan Round Tabel Discussion RSI Pekajangan
- 2. Dyslipidaemia and CVDRisk Most cardiovascular events and deaths attributable to raised blood pressure and dyslipidaemia occur among patients with blood pressure and lipid concentrations deemed normal. Intervention studies have confirmed the cardiovascular benefits of statins in primary prevention, secondary prevention and acute coronary syndromes across a wide age range and among patients with total cholesterol concentrations much lower than average. The lowering of cholesterol concentrations in individuals at high risk of cardiovascular disease improves outcome.
- 3. Conventional Risk Factorsfor Coronary Heart Disease 44 RRiisskk FFaaccttoorrss CCiiggaarreettttee SSmmookkiinngg HHyyppeerr-- lliippiiddeemmiiaa HHyyppeerr-- tteennssiioonn DDiiaabbeetteess • 8877%% ttoo 110000%% ooff ppaattiieennttss wwhhoo eexxppeerriieenncceedd aa ffaattaall ccoorroonnaarryy eevveenntt hhaadd aann aanntteecceeddeenntt eexxppoossuurree ttoo ³ 11 rriisskk ffaaccttoorr..** • >> 8800%% ooff ppaattiieennttss wwiitthh ccoorroonnaarryy ddiisseeaassee hhaadd ³ 11 ooff tthhee 44 ccoonnvveennttiioonnaall rriisskk ffaaccttoorrss..**** ** JJAAMMAA 22000033;;229900::889911 **** JJAAMMAA 22000033;;229900::889988
- 4. What is Dyslipidaemia? Dyslipidemias are disorders of lipoprotein metabolism Including lipoprotein overproduction & deficiency They may manifest as one or more of the following: Elevated total cholesterol, low-density lipoprotein cholesterol (LDL), & triglyceride levels or as decreased high-density lipoprotein cholesterol (HDL) level
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- 6. Lipid Metabolism Cholesterol synthesis Lipoproteins: VLDL LDL HDL Chylomicrons Apolipoproteins LDL receptor
- 7. How to AssessRisk? • Assess risk factors: CHD or CHD risk equivalent (regardless of number of risk factors) using NCEP ATP III definition of CHD & CHD risk equivalent ≥ 2 risk factors with no CHD & no CHD risk equivalent using NECP ATP III major risk factors that modify LDL goals • If ≥ 2 risk factors & no CHD or CHD risk equivalent: Assess global CHD risk by Framingham Point Score
- 8. CHD & CHDRisk Equivalent Clinical CHD Carotid artery disease Peripheral arterial disease Abnormal aortic aneurysm DM Myocardial ischemia (angina) Stroke history Claudication Present Present Myocardial infarction Transient ischemic attack history ABI > 0.9 Coronary angiography &/or stent replacement Carotid stenosis > 50% CABG Prior unstable angina Any of these present? Yes -------------------------------------------- CHD or CHD risk equivalent No ----- See if the patient has major risk factors that modify LDL goals NCEP ATP III Definition of CHD & CHD Risk Equivalent
- 9. Major Risk FactorsThat Modify LDL Goals Positive risk factors (↑ risk) Negative risk factors (↓ risk) Age: Male ≥ 45 yr High HDL (≥ 60 mg/dl) Female ≥ 55 yr Family history of premature CHD (definite MI or sudden death before 55 yr in father or other male first degree relative OR before 65 yr in mother or other female relative) Check if your patient has ≥ 2 risk factors Current cigarette smoking Hypertension (≥ 140/90 mm Hg or on antihypertensive drugs) Low HDL (< 40 mg/dl) NCEP ATP III Major Risk Factors That Modify LDL Goals
- 10. Framingham Point Score When to use it? • If the patient has CHD or CHD risk equivalent • ≥ 2 risk factors & no CHD or CHD risk equivalent • < 2 risk factors NO Yes NO
- 11. Framingham Point Score • It defines the 10 year risk of developing CHD • Framingham Point Score Male • Framingham Point Score Female
- 16. How to Assess: Your patient must fall in one of 3 categories: • If the patient has CHD or CHD risk equivalent • ≥ 2 risk factors & no CHD or CHD risk equivalent • < 2 risk factors No need to use Framingham score because these patients already have ≥ 20% risk of CHD in 10 years without any calculation Use to Framingham score to assess their 10 year risk No need to use Framingham score because they already have low risk for CHD
- 17. Classification of LipidLevels Total cholesterol mg/dl LDL cholesterol mg/dl < 200 Desirable < 100 Optimal 200-239 Border line high 100-129 Near optima/Above optimal ≥ 240 High 130-159 Borderline high 160-189 High ≥ 190 Very high NCEP ATP III Classification of Blood Lipids
- 18. Classification of LipidLevels Triglycerides mg/dl HDL cholesterol mg/dl < 150 Normal < 40 Low 150-199 Border line high 200-400 High ≥ 60 High ≥ 500 Very high NCEP ATP III Classification of Blood Lipids
- 19. Secondary Causes ofLipoprotein Abnormalities
- 20. Non Lipid RiskFactors for CHD Modifiable Risk Factors Non Modifiable Risk Factors Hypertension Age Cigarette smoking Male Thrombogenic/ hemostatic state Family history of premature CHD Diabetes Obesity Physical inactivity Atherogenic Diet
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- 22. Therapeutic Life StyleChanges Nutrient Recommended intake Total fat 25-35% of total calories Saturated fate < 7% of total calories Polyunsaturated fat Up to 10% of total calories Monounsaturated fat Up to 20% of total calories Carbohydrates 50-60% of total calories Fiber 20-30 g/day Cholesterol < 200 mg/day Protein 15% of total calories
- 23. Therapeutic Life StyleChanges Other life style changes include: • Weight reduction specially in overweight patients (reduce 10% in the first 6 months) • Increase physical activity • Smoking cessation
- 24. Dietary Adjuncts: Efficacyaatt RReedduucciinngg LLDDLL--CC Therapy Dose (g/day) Effect Dietary soluble fiber 2-8 ¯ LDL-C 5-10% Soy protein 20-30 ¯ LDL-C 5-7% Stanol esters 1.5-4 ¯ LDL-C 10-15% Jones PJ. Curr Atheroscler Rep 1999;1:230-235 Lichtenstein AH. Curr Atheroscler Rep 1999;1:210-214 Rambjor GS et al. Lipids 1996;31:S45-S49 Ripsin CM et al. JAMA 1992;267:3317-3325
- 25. Approximate Mortality ReductionPotential of Drug Vs Lifestyle Interventions in Patients with Coronary Disease* DDrruugg LLiiffeessttyyllee Low dose aspirin 18% Statins 21% ßß Blockers 23% ACE Inhibitors 26% Smoking cessation 35% Physical activity 25% Moderate alcohol 20% Combined lifestyle changes 45% IIeessttrraa JJAA eett aall.. CCiirrcc 2000055;11112::99244
- 26. Drug Therapy forDyslipidemia • Bile acid resins • Ezetimibe • Niacin • Statins • Fibric acid derivatives • Fish oil • Postmenopausal drug therapy
- 27. ATORVASTATIN : HHMMGG--CCooAARReedduuccttaassee IInnhhiibbiittoorr MMeecchhaanniissmm ooff AAccttiioonn Acetyl CoA Inhibition of the Cholesterol Biosynthetic Pathway HMG-CoA Mevalonate Farnesyl pyrophosphate Squalene Cholesterol Squalene synthase Dolichol Farnesyl-transferase Farnesylated proteins E,E,E-Geranylgeranyl pyrophosphate Geranylgeranylated proteins Ubiquinones HMG-CoA Reductase ATORWIN 10 & 20
- 30. Clinical Trials TrialIntervention Initial LDL Change in LDL CHD event reduction Acute coronary syndrome patients MIRACL Atorvastatin 124-72 ↓ 42% ↓ 26% AVERT Atorvastatin 145-77 ↓ 42% ↓ 36% Patients without evidence of CHD ASCOT Atorvastatin 132-85 ↓ 31% ↓ 50%
- 31. ATORVASTATIN :: PPrriimmaarryyPPrreevveennttiioonn Anglo-Scandinavian Cardiac Outcomes Trial—Lipid Lowering Arm (ASCOT-LLA) 10,305 patients with HTN randomized to atorvastatin (10 mg) or 4 3 2 1 0 Atorvastatin 90 mg/dl* Placebo 126 mg/dl* 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 CHD=Coronary heart disease, RR=Relative risk Sever PS et al. Lancet. 2003;361:1149-1158 P=0.0005 Cumulative incidence of MI and fatal CHD (%) Follow-up (yr) 36% RRR *Post-treatment LDL-C level placebo for 5 years Statins provide significant benefit in moderate- to high-risk individuals by lowering LDL-C levels below current goals ATORWIN 10 & 20
- 32. AATTOORRVVAASSTTAATTIINN :: SSeeccoonnddaarryyPPrreevveennttiioonn Myocardial Ischemia Reduction with Aggressive Cholesterol 3,086 pts with an ACS randomized to atorvastatin (80 mg) or placebo for 16 15 10 5 0 Lowering (MIRACL) Trial 17.4% 14.8% RR=0.84, P=0.048 Combined cardiovascular event rate (%)* Atorvastatin Placebo 0 4 8 12 16 Weeks *Includes death, MI resuscitated cardiac arrest, recurrent symptomatic myocardial ischemia requiring emergency rehospitalization. Schwartz GG et al. JAMA 2001;285:1711-1718 weeks Acute intensive treatment significantly reduces event rates ATORWIN 10 & 20
- 33. AATTOORRVVAASSTTAATTIINN:: SSeeccoonnddaarryy PPrreevveennttiioonn Pravastatin or Atorvastatin Evaluation and Infection Therapy 4,162 pts with an ACS randomized to atorvastatin (80 mg) or pravastatin (40 mg) for 24 months 3 6 9 12 15 18 21 24 27 30 Follow-up (months) 30 25 20 15 10 5 0 P =0.005 Recurrent MI, cardiac death, UA, revascularization, or stroke 16% RRR (PROVE-IT)—TIMI 22 Study Atorvastatin Pravastatin Acute intensive treatment significantly reduces event rates ACS=Acute coronary syndrome, CV=Cardiovascular, MI=Myocardial infarction, UA=Unstable angina Cannon CP et al. NEJM 2004;350:1495-1504 ATORWIN 10 & 20
- 34. AATTOORRVVAASSTTAATTIINN:: SSeeccoonnddaarryy PPrreevveennttiioonn 10,001 patients with stable CHD randomized to atorvastatin (80 mg) or atorvastatin (10 mg) for 4.9 years Years Major CV Event* (%) P<0.001 0 1 2 3 4 5 6 22% RRR Treating to New Targets (TNT) Trial Atorvastatin (10 mg) Atorvastatin (80 mg) 0.15 0.10 0.05 0.00 High-dose statins provide benefit in chronic CHD CHD=Coronary heart disease, CV=Cardiovascular, MI=Myocardial infarction, RRR=Relative risk reduction *Includes CHD death, nonfatal MI, resuscitation after cardiac arrest, or stroke LaRosa JC et al. NEJM 2005;352:1425-35 ATORWIN 10 & 20
- 35. AATTOORRVVAASSTTAATTIINN:: SSeeccoonnddaarryy PPrreevveennttiioonn Incremental Decrease in End Points Through Aggressive Lipid Lowering (IDEAL) Trial 8,888 patients with a history of acute MI randomized to atorvastatin (80 mg) Cumulative Hazard (%) 12 8 or simvastatin (20 mg) for 5 years Simvastatin (20 mg) Atorvastatin (80 mg) 0 1 2 3 4 5 Years Since Randomization 4 HR=0.89, P=0.07 High-dose statins provide a strong trend towards benefit HR=Hazard ratio, MI=Myocardial infarction *Includes coronary death, hospitalization for nonfatal acute MI, or cardiac arrest with resuscitation Pedersen et al. JAMA 2005;294:2437-2445 after a MI ATORWIN 10 & 20
- 36. ACS Patients: MajorCoronary Events MI + CHD Death + Resuscitated Cardiac Arrest Incremental Decrease in End Points Through Aggressive Lipid Lowering (IDEAL) Trial Simvastatin Atorvastatin Years Since Randomization Cumulative Hazard (%) 0 1 2 3 4 5 20 16 12 8 4 0 34% RRR HR = .66 (95% CI = 0.46, 0.95), P=.02 Pedersen, Olsson, Cater et al. WCC, 2006 ATORWIN 10 & 20
- 37. SUMMARY – Loweris better • LDL • CRP • Triglycerides (and probably) higher is better for HDL – LDL cholesterol as a primary target of therapy – Studies showed that Atorvastatin proof was in better CVD risk prevention – ATORWIN as new Atorvastatin can be as a new choice with high quality product, right dose and right price
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Editor's Notes
- #6 Atorvastatin inhibit the HMG-CoA Reductase enzyme which leads to a reduction in hepatic intracellular cholesterol.
- #25 A healthy diet, that includes increased amounts of whole grains, fiber, fruits, vegetables, soy protein, and stanol esters, can significantly reduce levels of LDL-C.
- #28 Atorvastatin inhibit the HMG-CoA Reductase enzyme which leads to a reduction in hepatic intracellular cholesterol.
- #32 ACSCOT-LLA was a substudy of the ASCOT trial and sought to assess the benefits of cholesterol reduction in the primary prevention of coronary heart disease in hypertensive patients not deemed hypercholesterolemic (total non-fasting cholesterol &lt;250mg/dl) by conventional means. All patients had to have at least three other cardiovascular risk factors making this a moderate to high risk population. Patients were randomized to treatment with atorvastatin (10 mg) or placebo. The primary endpoint was non-fatal MI and fatal CHD by an intention to treat analysis. The study was stopped after 3.3 years due to a significant reduction in the primary endpoint in the atorvastatin arm compared to placebo, hazard ratio 0.64 [95% CI 0.50-0.83], p=0.0005. Importantly, differences were noted in the first year of treatment and the LDL-C levels attained were lower than current goals. There was no significant difference in death between the two arms.
- #33 The MIRACL trial was the first large scale study to evaluate the effects of acute intensive statin therapy in the secondary prevention setting. Compared to placebo, treatment with atorvastatin (80 mg) within 96 hours of an acute coronary syndrome resulted in a 16% relative risk reduction in the primary end point (death, nonfatal acute myocardial infarction, cardiac arrest with resuscitation, or objective evidence of recurrent symptomatic myocardial ischemia requiring emergency rehospitalization) in the first 16 weeks of treatment. There were no significant differences in the risk of death, nonfatal myocardial infarction, or cardiac arrest in the two arms of the study. The difference in the primary endpoint was driven by a lower risk of symptomatic ischemia requiring emergency rehospitalization (6.2% vs. 8.4%; RR, 0.74; 95% CI, 0.57-0.95; P =0.02). Treatment with atorvastatin resulted in a mean decrease in LDL-C from 124 mg/dL to 72 mg/dL. There was a significant increase in hepatic transaminases &gt;3x the upper limit of normal with atorvastatin as compared to placebo (2.5% vs 0.6%; P&lt;.001).
- #34 PROVE IT-TIMI 22 was designed to assess the effects of early statin therapy in individuals with an acute coronary syndrome. In a head-to-head comparison of statin regimens, patients were randomized to a high dose potent statin (atorvastatin 80 mg) or a moderate dose less potent statin (pravastatin 40 mg) over a mean follow-up of 24 months to determine if intensive statin therapy was associated with a lower event rate. Use of atorvastatin and pravastatin resulted in on-treatment mean LDL-C levels of 62 mg/dL and 95 mg/dL, respectively. The primary end point (a composite of death from any cause, myocardial infarction, documented unstable angina requiring rehospitalization, recurrent revascularization, or stroke) occurred in 22.4% of individuals on atorvastatin vs. 26.3% of individuals on pravastatin, p=0.005. This effect of intensive statin therapy set a new benchmark for aggressive early LDL-C lowering in acute coronary syndromes.
- #35 Following the Heart Protection Study, the TNT study sought to determine whether high dose statin therapy provided additional cardiovascular benefit among individuals with chronic coronary heart disease. All patients entered an open-label eight week period with low dose atorvastatin (10 mg), those who experienced a statin related side effect or did not achieve an LDL-C level &lt;130 mg/dL were excluded prior to randomization. High dose atorvastatin (80 mg) resulted in a significant 22% relative risk reduction in the primary composite endpoint (death from coronary heart disease, nonfatal MI, resuscitation after cardiac arrest, and fatal or nonfatal stroke) as compared to low dose atorvastatin (10 mg). Paralleling the reduction in the composite primary endpoint was a decrease in the LDL-C levels to 77 mg/dL and 101 mg/dl in the high and low dose atorvastatin arms, respectively. There were no differences in overall mortality. These results add to the body of data obtained in the PROVE IT-TIMI 22 and HPS trials, demonstrating a benefit with lower LDL-C levels in individuals with coronary heart disease.
- #36 The Incremental Decrease in End Points Through Aggressive Lipid Lowering (IDEAL) study evaluated the effect of intensive vs. moderate lipid lowering therapy in patients with a history of MI. Patients were randomized to receive atorvastatin (80 mg) or simvastatin (20 mg) over a mean period of 5 years. The primary endpoint was occurrence of a major coronary event, defined as coronary death, confirmed nonfatal acute MI, or cardiac arrest with resuscitation. There was no significant difference in the primary endpoint (HR 0.89, 95% CI, 0.78-1.01, p=0.07), despite an LDL-C difference of 23 mg/dL (81 mg/dL vs. 104 mg/dl in the atorvastatin vs. simvastatin treatment groups, respectively). There was, however, a significant reduction in nonfatal MI (6.0% vs. 7.2% respectively, p=0.02), major cardiovascular events, and any coronary event. There was no difference in mortality endpoints between the two groups. Importantly, the primary endpoint did not include stroke. When stroke was added to the primary end point, however, the relative risk reduction was similar to that seen in the TNT study.