Is the Controlled Rosuvastatin Multinational Study in Heart Failure (CORONA) the Answer to the Cholesterol Paradox in Heart Failure?

In the previous issue of Congestive Heart Failure, we examined the apparent paradox of possible benefit with statin therapy despite low cholesterol being an adverse prognostic marker in patients with heart failure (HF).1 Since we wrote the paper, the Controlled Rosuvastatin Multinational Study in Heart Failure (CORONA) trial has been published.2 CORONA was a large multicenter trial of 5011 patients of at least 60 years of age (mean, 73±7 years) with New York Heart Association classes II through IV symptoms and HF due to left ventricular systolic dysfunction (mean ejection fraction, 0.31±0.07) secondary to underlying ischemic heart disease. Patients were randomized to rosuvastatin 10 mg or placebo. Median follow-up was 32.8 months. Rosuvastatin did not reduce the number of deaths from any cause or the primary outcome, a composite end point comprising death from cardiovascular causes, nonfatal myocardial infarction, or stroke. As expected with a potent lipid-lowering drug, there was a substantial reduction in the levels of low-density lipoprotein cholesterol and high-sensitivity C-reactive protein in the rosuvastatin group. There was no reduction in the number of patients hospitalized, but a significant reduction in the total number of hospitalizations was noted in the rosuvastatin group. There was no excess of muscle-related or other adverse events observed with rosuvastatin. Although the results of CORONA were neutral, a number of questions remain unanswered. As noted in the accompanying editorial,3 a class effect of statins cannot be assumed, as we know from experience with cerivastatin. CORONA was limited to patients with ischemic HF, already on evidence-based therapy with β-blockers and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. It is possible that some beneficial effect of rosuvastatin might be more important in patients with nonischemic HF or those with HF and preserved left ventricular function. It is also possible that there might be a small benefit of rosuvastatin in younger patients who are hence going to be followed-up for a longer time. This effect was not observed in older patients with a shorter follow-up, since the atherosclerotic process in younger patients could be modified by statin therapy. The ongoing Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico-Insufficienza Cardiaca (GISSI-HF) trial examining the effect of rosuvastatin in HF, which included patients with HF not due to ischemic heart disease and patients with preserved systolic function, might provide an answer to some of these unresolved questions. —Periaswamy Velavan, MBBS, MD, MRCP(UK); Poay Huan Loh, MB BCh, BMedSc, MRCP; Andrew Clark, MA, MD, FRCP; John G. F. Cleland, FRCP, Cardiothoracic Centre, Liverpool, and the Department of Academic Cardiology, University of Hull, UK Dr Cleland was a member of the CORONA study group.