What is New About Statins? M Mohsen Ibrahim, MD

Transcription

1 What is New About Statins? M Mohsen Ibrahim, MD

2 What is new about statins? Role in Acute coronary syndromes. Regression of atherosclerosis. Prevention of stroke. Role in heart failure. Prevention of diabetes mellitus.

3 Rationale For Statins In ACS Revascularization procedures do not modify underlying pathophysiology and only modestly reduce the risk of subsequent events Statins contribute to plaque stability and/or regression through a number of lipiddependent and -independent (pleiotropic) mechanisms Schwartz and Olsson. Am J Cardiol. 2005;96(suppl):45F.

4 How do statins work? STATINS PREVENT PLAQUE RUPTURE Change plaque character Strengthen the fibrous cap Inhibit the inflammation sequence Inhibit matrix degradation

5 Change in Plaque Character Plasma LDL-C LDL-C entry Esterification Smaller lipid core More solid plaque

6 STATINS Antithrombotic Effects Platelet aggregration Tissue factor expression (monocytes/macrophages) PAI-1 expression (VSMCs& ECs) tpa expression ( ECs)

7 Effect of lipid-lowering therapy on early mortality after acute coronary syndromes: an observational study GUSTO IIb) (PURSUIT, % mortality with statin (n=3,653) no statin (n=17,156) P< P< day 6-months Aronow H et al. Lancet 2001; 357:

8 The Randomized Lipid-Coronary Artery Disease (L-CAD): Effects of Treatment with Pravastatin Immediately After a Coronary Event % of Combined end-points Death, nonfatal MI, stroke, or new onset of peripheral vascular disease Usual care (n=56) P= Statin therapy (n=70) 52% 23% Months of Observation Arntz H-R et al. Am J Cardiol 2000;86:

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10 Euro Heart Survey on Acute Coronary Syndromes-2006 Patients using statin treatment within 24 h after admission for ST-elevation acute coronary syndromes had lower mortality than non-users Mortallity Timo Lenderink1, Eric Boersma2, Anselm K. Gitt3, Uwe The Kaplan Meier curves for mortality in all patients surviving the first 24 h and stratified according to statin treatment within 24 h after hospitalization. European Heart Journal published online on July 4, 2006

11 Statins in ACS In patients recently hospitalized within 10 days for an acute coronary syndrome: Benefits emerged within 30 days post ACS with continued benefit observed throughout the 2.5 years of follow-up

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13 Cardiology Department Cairo University Intravascular Ultrasound Initial study Simvastatin 40 mg OD Six months

14 Cardiology Department Cairo University Gray-Level Color Coding Initial study Simvastatin 40 mg OD Six months

15 ASTEROID Trial: Primary Endpoint cont. % patients Regression vs. progression change in % atheroma volume (%) Regression in percent atheroma volume was observed in 63.6% of patients; whereas, progression was observed in 34.6% Regression www. Clinical trial results.org Progression Presented at ACC 2006

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18 Statin Therapy in Heart Failure Clinical Trials Retrospective/ Prospective/ Observational Randomized Ongoing S - Diastolic HF -CORONA -ELITE II -Simvast HF - GISSI-HF -Cardiomyopathy -Cerivast nonisch-cm clinic -Atorvast EF - PRAISE -Elderly population

19 Statins Benefit in HF : Possible Mechanisms Slow progression of ASO. Reduce atrial and vent arrhythmias. Improve endothelial function. Reduce aortic stiffness. Reduce inflammation. Reduce oxidative stress. Reduce LV hypertrophy. Prevent LV remodeling. Reduce neurohormonal activation.

20 The effects of simvastatin on the incidence of heart failure in patients with coronary heart disease *1, *2 John Kjekshus, a, b, c, d,, Terje R. Pedersen b, c, d, a, Anders G. Olsson b, c, d, a,

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23 PRAISE trial Statin Therapy Is Associated With Lower Mortality Among Patients With Severe Heart Failure : Dariush Mozaffarian, Regina Nye, and Wayne C. Levy, AM J Card 2004

24 Foody et al. reduction in mortality risk 1 y : 20% 3 y : 18% Statins and Mortality among Elderly Patients Hospitalized with HF

25 torvastatin Improves Left Ventricular Systolic Function and Serum Markers of nflammation in Nonischemic Heart Failure rikanth Sola, MD *, Muhammad Q.S. Mir, MD *, Stamatios Lerakis, MD, FACC, Neeraj Tandon, MD, FACC and Bobby V. Khan, MD, PhD *, *

26 Patients With Diastolic Heart Failure Hidekatsu Fukuta, MD; David C. Sane, MD; Steffen Brucks (Circulation 2005)

27 Hidekatsu Fukuta, MD; David C. Sane, MD; Steffen Brucks, MD; William C.. Little, MD (Circulation )

28 Statin Therapy in Heart Failure Large Ongoing Studies CORONA pts with ischemic HF - Rosuvastatin (10 mg) vs placebo - Death+MI+Stroke / Death GISSI-HF pts with clinical HF - Rosuvastatin (10 mg) vs placebo - Death / Death+CV hospitalization

29 WOSCOPS: Effect of Pravastatin on Development of Diabetes 4 Percent Diabetic Placebo Pravastatin 30% RRR p< Years in Study Freeman DJ et al. Circulation 2001;103:

30 Statins & the Development of Diabetes Mellitus * Anti-inflammatory effects The Anti-inflammatory effects include reducing levels of cytokines wich may interrupt the natural progression from central obesity to insulin resistance * Restored endothelial function Impaired endothelial function diminishes selective tissue perfusion which affects glucose and insulin transport => Diab * Lower triglyceride levels Elevated triglyceride levels are known to be associated with the development of type 2 diabetes Freeman DJ et al. Circulation 2001;103: