CORONA: Rosuvastatin 'neutral' in elderly with ischemic HF

zyc50

6 November 2007

MedWire News: The addition of a statin to optimized heart failure (HF) therapy cannot prevent the deterioration of failing heart muscle in elderly patients, reveal the CORONA findings unveiled at the American Heart Association's Annual Scientific Sessions in Orlando, Florida.

The CORONA trial, which involved rosuvastatin treatment, did not meet its primary endpoint of reducing cardiovascular (CV) deaths and events compared with placebo in elderly patients with ischemic systolic heart failure.

However, rosuvastatin was associated with fewer thrombotic CV events and hospitalizations for CV causes, without any increase in adverse events, emphasized CORONA investigator 舓e Hjalmarson (Sahlgrenska University Hospital, Gothenburg, Sweden).

Subgroup analyses of various trials have indicated that statins may benefit HF patients, but HF patients have largely been excluded from statin trials. CORONA (Controlled Rosuvastatin Multinational Trial in HF) compared clinical outcomes for rosuvastatin 10 mg daily versus placebo specifically in HF patients.

The trial enrolled 5011 patients with systolic HF of ischemic origin who were aged 60 years or over, were in New York Heart Association (NYHA) functional class II or III/IV, and had received optimal medical therapy.

The results, published simultaneously online by the New England Journal of Medicine, show that the patients' mean low-density lipoprotein level was reduced by 45% with rosuvastatin compared with placebo at 3 months. This difference was more or less maintained for the whole study, Hjalmarson noted. C-reactive protein levels were also significantly and consistently lowered by rosuvastatin.

Over a median follow-up of 33 months there was only a small difference in the primary composite endpoint of CV death or non-fatal myocardial infarction (MI) or nonfatal stroke between rosuvastatin- and placebo-treated patients. At the end of follow-up, the primary endpoint rates were 27.5% and 29.3% in the rosuvastatin and placebo groups, respectively, which translated into a nonsignificant 8% relative risk reduction with rosuvastatin.

However, a post-hoc analysis showed a lower rate of nonfatal or fatal MI or stroke in patients who received rosuvastatin compared with those who received placebo (9.0% vs 10.6%, hazard ratio [HR]=0.84; p=0.05). Hjalmarson noted that this discordance with the primary endpoint was explained by the high proportion of cardiovascular deaths, which accounted for 68% of the primary events.

\"If we assume rosuvastatin did reduce the risk of acute atherothrombotic events, which has been seen in all the other statin trials, our results suggest that the major etiology of CV deaths... may be a primary electrical event, related to ventricular dilation and scarring, and not to a new atherothrombotic event,\" he said.

Rosuvastatin treatment was also associated with significantly fewer all cause (p=0.007), CV cause (p<0.001), and HF (p=0.01) hospitalizations.

Finally, there was no increase in adverse events with rosuvastatin. The rate of premature, permanent discontinuation, including that due to adverse events was actually higher in patients taking placebo than those on rosuvastatin. In particular, muscle-related symptoms were no more common with the study drug.

Commenting on the results, Hjalmarson said that statin treatment in very elderly and sick HF patients may not have sufficient time to influence the clinical course of their disease. The study did not address potential differences in treatment effects according to HF severity, he said, but subgroup analysis would suggest that younger patients with less severe HF may benefit from statin treatment.

In an editorial accompanying the New England Journal of Medicine paper, Frederick Masoudi (University of Colorado, Denver, USA) commented that the lack of benefit with rosuvastatin may simply reflect that statins as a class have no effect in patients with ischemic left ventricular dysfunction receiving evidence-based therapy, \"a group that may be less prone to CV ischemic events compared with those entered into earlier statin secondary-prevention trials.\"

However, he said that the reduction in hospitalizations with rosuvastatin treatment was \"reassuring\" and noted that the study made \"important strides\" in including a representative patient population.