Treatment with rosuvastatin in older patients with moderate to severe chronic ischemic heart failure due to left ventricular systolic dysfunction did not reduce the risk of death from cardiovascular causes or the rate of nonfatal myocardial infarctions and stroke in the randomized Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA) presented at the annual scientific sessions of the American Heart Association.
Data from studies of statin use in patients with ischemic or nonischemic heart failure have suggested the use of statins is associated with better outcomes and beneficial effects on left ventricular function and clinical status, said the CORONA investigators.
“Doctors took for granted that statins should work in everyone with coronary artery disease,” including those with heart failure, even though there had been no placebo-controlled trial of statins in heart failure patients, said Dr. Åke Hjalmarson, at a news conference at the meeting. The results were published concurrently with the news conference in the New England Journal of Medicine (N. Engl. J. Med. 2007 Nov. 5 [Epub doi:10.1056/NEJMoa0706201]).
But the reportedly low rates of myocardial infarctions in patients with ischemic heart failure (despite having high rates of coronary artery disease), as well as possible adverse effects of the drugs, have called the use of statins in these patients into question, reported Dr. Hjalmarson of the University of Oslo, and his coinvestigators.
They were concerned with possible adverse effects of rosuvastatin on the function of skeletal and cardiac muscle, the kidneys, and the liver, but found muscle-related symptoms and elevations in creatine kinase and alanine aminotransferase levels occurred at similar rates between the rosuvastatin and placebo groups. The drug also did not further reduce LDL cholesterol in patients with already low levels.
These factors suggest “clinicians should continue [prescribing] statins for patients with ischemic heart failure and left ventricu-lar systolic dysfunction,” said Dr. Masoudi.
The patients had a mean age of 73 years and for entry into the study, had to be at least 60 years old, have chronic heart failure due to ischemia with a New York Heart Association class of II-IV, and an ejection fraction no more than 40% (no more than 35% in class II patients); the investigators also had to think that a patient did not need treatment with a cholesterol-lowering drug.
At the end of the trial's median follow-up time of nearly 33 months, there was an 8% relative reduction in the primary outcome—a composite of death from cardiovascular causes, nonfatal myocardial infarction, and nonfatal stroke—in the treated patients, a nonsignificant difference. In the 2,514 patients treated with 10 mg/day rosuvastatin, 692 reached the primary end point, compared with 732 of the 2,497 patients who received placebo. The event rates (number of events per 100 patient-years of follow-up) were 11.4 and 12.3 for the treated and placebo patients, respectively. This effect was consistent across a range of different subgroups of patients.
In a post hoc analysis, rosuvastatin significantly reduced the total number of fatal and nonfatal myocardial infarction and stroke events, compared with placebo (227 vs. 264). For rosuvastatin-treated patients, this translated into a 16% lower relative risk than placebo-treated patients. The drug had no significant effect on cardiovascular mortality, which accounted for 68% of all events in the primary composite outcome, said Dr. Hjalmarson, professor of cardiology at the Wallenberg Laboratory for Cardiovascular Research at Sahlgrenska University Hospital, Göteborg, Sweden. “The major etiology of cardiovascular deaths … may be a primary electrical event relating more to ventricular dilatation and scarring and not to a new atherothrombotic event.” Many of the researchers reported getting consulting, advisory board, and/or lecture fees from AstraZeneca, which funded the study and makes rosuvastatin.