Journal Club Presentation

1. Journal Club Presentation Kendra Marsh, MD Department of Cardiology University of Illinois at Chicago November 27, 2007

2. CORONA TRIALControlled Rosuvastatin Multinational Trial in Heart Failure

3. Background • A large percentage of patients with left ventricular dysfunction have coronary artery disease. • Few of these patients have myocardial infarctions • Statin therapy has been shown to be beneficial in the treatment of coronary artery disease and prevention of myocardial infarction. • Patients with severe LV dysfunction often have lower cholesterol, yet they have worse outcomes.

4. Potential harm of Statins in Heart Failure • Lipoproteins are postulated to remove endotoxins that seep in through the intestinal wall. • Decreased synthesis of Co-Enzyme Q10 • A co-factor in the mitochondrial electron transport chain • Antioxidant • Decreased production of Selenoproteins • Resulting in skeletal and cardiac myopathies

5. Potential Benefit of Statins in Heart Failure • Improves endothelial function • Anti-inflammatory activity

6. Hypothesis • The beneficial results of Rosuvastatin would out-way any theoretical hazards, improve survival, reduce morbidity and increase well being in patients with chronic, symptomatic, systolic ischemic heart failure.

7. Characteristics of the Patients Patient Characteristics Kjekshus J et al. N Engl J Med 2007;10.1056/NEJMoa0706201

8. Method • Inclusion criteria • Population: 19 European countries, Russia, South Africa • 60 years or older • New York Heart Association Class II, III or IV • Ejection Fraction less than 40% • Stable medical therapy for 2 weeks

9. Method • Exclusion Criteria • Previous adverse reaction to statin ( myopathy or hypersensitivity • Decompensated Congestive Heart Failure • Inotropic Therapy • Myocardial Infarction in the past 6 months • Unstable Angina or Stroke within the past 6 months • PCI/CABG/ICD/Biventricular pacemaker within 3 months • Previous or planned heart transplant • Uncorrected primary heart valve • Malfunctioning prosthetic valve • Pericardial or endocardial disease • Abnormal LFT’s • Less than 80% of placebo taken • Abnormal Creatinine Kinase • Poor Compliance

10. Study Design • Single blinded placebo-control trial. • Rosuvastatin 10 mg oral vs. Placebo • Follow up at 6 weeks and 3 months • If patient was doing well, follow up at 6 months, 15 months and then yearly. • Liver Enzymes were checked at 3 months ad then yearly

11. Target Outcomes • Primary Outcomes: Composite • Death (Cardiovascular), Non-fatal MI, Non-fatal stroke • Secondary Outcomes • Death, any cause • Any cardiac event: sudden cardiac death, fatal or non fatal MI • Revascularization: PCI, CABG • Hospitalization for unstable angina • Worsening CHF

12. Statistical Analysis • Anticipated mean Hazard ratio 10.4 % • Projected time for rosuvastatin to show significant effect, 10 months • To achieve a 16% reduction in primary outcomes, a statistical power of 90% was used to detect such a change. • Therefore the projected number of patients needed was 4950. • People were enrolled with intention to treat.

13. Results

14. Figure 1. Kaplan–Meier Estimates for the Primary Outcome, Death from Any Cause, and Any Coronary Event.

20. Discussion • Rosuvastatin 10mg Qdaily did not reduce primary outcomes • Cardiovascular hospitalizations were significantly reduced • There were no significant adverse events when compared to placebo.

21. Limitations • Older patients • Potentially statin naive with advanced CAD • NYHC III, IV • Perhaps the study should have been extended over a longer period of time • Diastolic Dysfunction, Nonishemic Cardiomyopathy patients not included • Unusually compliant group of patients • Selection bias for patients who would have good follow up.

22. Thank you!