Transcript Journal Club Presentation

Journal Club Presentation
Kendra Marsh, MD
Department of Cardiology
University of Illinois at Chicago
November 27, 2007
CORONA TRIAL
Controlled Rosuvastatin
Multinational Trial in Heart
Failure
Background
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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.
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
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A co-factor in the mitochondrial electron
transport chain
 Antioxidant
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Decreased production of Selenoproteins
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Resulting in skeletal and cardiac myopathies
Potential Benefit of Statins in Heart
Failure
Improves endothelial function
 Anti-inflammatory activity
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Hypothesis
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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.
Characteristics of the Patients
Patient Characteristics
Kjekshus J et al. N Engl J Med 2007;10.1056/NEJMoa0706201
Method
Inclusion criteria
 Population: 19 European countries,
Russia, South Africa
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60 years or older
 New York Heart Association Class II, III or IV
 Ejection Fraction less than 40%
 Stable medical therapy for 2 weeks
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Method
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Exclusion Criteria
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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
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
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Target Outcomes
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Primary Outcomes: Composite
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Death (Cardiovascular), Non-fatal MI, Non-fatal stroke
Secondary Outcomes
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Death, any cause
Any cardiac event: sudden cardiac death, fatal or non
fatal MI
Revascularization: PCI, CABG
Hospitalization for unstable angina
Worsening CHF
Statistical Analysis
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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.
Results
Figure 1. Kaplan–Meier Estimates for the
Primary Outcome, Death from Any Cause, and
Any Coronary Event.
Discussion
Rosuvastatin 10mg Qdaily did not reduce
primary outcomes
 Cardiovascular hospitalizations were
significantly reduced
 There were no significant adverse events
when compared to placebo.
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Limitations
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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.
Thank you!