Statin has no effect on cardiovascular outcomes in advanced systolic heart failure

November 7, 2007

In older patients with advanced systolic heart failure, rosuvastatin added to standard heart failure medications failed to significantly reduce incidence of a composite of cardiovascular death, nonfatal myocardial infarction (MI), and nonfatal stroke compared with placebo, although it did reduce the incidence of all-cause and cardiovascular-related hospitalizations.

In older patients with advanced systolic heart failure, rosuvastatin added to standard heart failuremedications failed to significantly reduce incidence of a composite of cardiovascular death, nonfatalmyocardial infarction (MI), and nonfatal stroke compared with placebo, although it did reduce theincidence of all-cause and cardiovascular-related hospitalizations.

Rosuvastatin did result in fewer nonfatal MIs and nonfatal strokes but had no effect oncardiovascular death, which accounted for two-thirds of the primary events in the study, known asCORONA (Controlled Rosuvastatin Multinational Trial in Heart Failure).

The study's principal investigator, Ake Hjalmarson, MD, PhD, said that these findings suggest that"the major etiology of cardiovascular deaths in this older, vulnerable category of otherwisewell-treated patients with advanced systolic heart failure may be a primary electrical event relatedto ventricular dilatation and scarring, and not to an atherothrombotic event."

In CORONA, 5011 patients with class II to IV systolic heart failure of ischemic etiology who did nothave an indication for lipid-lowering therapy were randomized to rosuvastatin, 10 mg/d, or placebo ontop of optimal heart failure medications. To be eligible, patients with class II heart failure had tohave an ejection fraction of 0.35 or less, and patients with class III or IV heart failure had tohave an ejection fraction of 0.40 or less. The mean age of patients enrolled was 73 years.

At a median follow-up of 33 months, rosuvastatin was associated with a nonsignificant 8% reduction inthe incidence of adverse cardiovascular outcomes. A post-hoc analysis showed a significant 16%reduction in the incidence of nonfatal or fatal MI or stroke in those assigned to rosuvastatin(P =.05).

There were significantly fewer hospitalizations for any cause (P =.007), for cardiovascularcauses (P P =.01) in the rosuvastatin group.

Dr Hjalmarson, professor of cardiology, at Sahlgrenska University Hospital, said that theintervention may have come too late to modify the course of the disease in these patients with moreadvanced forms of heart failure. "It might well be that younger patients with less severe heartfailure might have a benefit," he said. But for older heart failure patients with a short lifeexpectancy, "there's no reason to start a statin," he said.

Rosuvastatin was exceptionally safe in these patients, he added. There was no excess of a significantelevation in liver transaminase levels, muscle-related symptoms, or elevations of creatine kinaselevels in patients who received rosuvastatin.