Statins in heart failure: Prospective trials required

September 07, 2004

Tue, 07 Sep 2004 20:15:00

Munich, Germany - Two new post hoc analyses of chronic heart-failure (HF) trials suggest that statins appear to be of benefit in this patient population, attendees at the European Society of Cardiology Congress 2004 heard last week. But confirmation of these effects is nevertheless needed and should come from large prospective trials that are under way, researchers said.

Dr Roberto Latini (Mario Negri Institute, Milan, Italy) presented findings on patients taking statins in the Val-HeFT study, and Dr Henry Krum (Monash University, Melbourne, Australia) reported data on statin users in the CIBIS-II trial.

Both doctors explained that the role of statins in patients with HF is unclear: although they are often prescribed, there is controversy about whether they have any benefit, and some studies have even suggested statins may be harmful in this patient population, as reported by heartwire .

VAL-HeFT: Largest nonrandomized sample of HF patients studied for statin effects

Latini explained, "Few studiesand none of them randomizedhave reported on the efficacy of, or outcomes with, statins in heart-failure patients." Hence, his team analyzed the VAL-HeFT database to assess the outcome of the 1602 patients with HF who were receiving statins at baseline, out of a total study population of 3048.

A multivariate Cox proportional hazards model with death as the outcome was used to assess the effect of statin use at baseline, adjusting for clinical risk factors statistically different at baseline.

 

There was significantly better survival in those on statins compared with those not on statins.

 

"There was significantly better survival in those on statins compared with those not on statins," Latini told the meeting. Mortality over a mean two-year follow-up was 17.9% on statins vs 20.3% without statins (p=0.029).

The hazard ratio for mortality was 0.81 in those on statins compared with those not on statins; for morbidity and mortality this figure was 0.87 (p=0.044). There was no significant interaction between statins and valsartan, however.

"This was the largest nonrandomized sample of patients with heart failure yet studied for the effect of statins on outcome," Latini said, adding that the benefits of statins "appear to be independent of creatinine and C-reactive protein [CRP]." Also, the reduction in mortality and morbidity and mortality with statins was larger in patients with baseline cholesterol below the median, he noted.

"In a large contemporary sample of patients with heart failure, statins appeared to be associated with a lower two-year mortality," Latini concluded. "The present analysis extends and supports previously published studies, which were conducted in nonrandomized populations."

In answer to questions from the audience, Latini said that although they did not record which specific statins were being used in VAL-HeFT, the main one that patients were taking was pravastatin (Pravachol®, Bristol-Myers Squibb).

There were also queries about the newer statin, rosuvastatin (Crestor®, Astra Zeneca), with delegates asking about reports in the literature suggesting that this drug could cause renal dysfunction. "I would wait a bit longer before making a decision on this," Latini said, adding: "I don't think it's fully explainable."

Another doctor wondered whether the effect of statins seen on mortality in VAL-HeFT "was not just an effect on ischemic heart disease [IHD] rather than left ventricular dysfunction." Latini replied that his team "had factored IHD into the Cox analysis, but of course we could do more work on this."

CIBIS-II analysisonly 8.5% of patients taking statins at baseline

Krum and colleagues conducted a post hoc analysis of outcomes according to statin use in CIBIS-IIa beta-blocker trial with bisoprolol (Zebeta®, Cardicor®, Merck)in patients with class 2 to 3 congestive heart failure (CHF).

In total, 226 of 2647 patients were receiving a statin at baseline (8.5%). There was no difference in all-cause mortality between those taking statins at baseline and those taking placebo. However, there was a highly significant interaction between statin and bisoprolol use. Survival was 98.3% in the statin/bisoprolol group, 82.1% in the statin/placebo group, 87.2% in the no statin/bisoprolol group, and 82.8% in the no statin/placebo group.

Worsening heart failure was also lower in those taking a statin and bisoprolol (7.5%) compared with those taking statin/placebo (13.2%), no statin/bisoprolol (12.4%), and no statin/placebo (18.0%).

But there are several caveats to the study, Krum noted. These include the fact that patients were not prospectively randomized, only a relatively small percentage of patients were taking statins at baseline, and the analysis did not take into account patients starting (or stopping) statin therapy after baseline.

Both Krum and Latini agreed that prospective trials in this area are much needed.

CORONA and GISSI-HF will yield more information

Two definitive prospective trials of statins in heart failure will provide much more information, the doctors said. These include the GISSI-HF trial and the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA), both of which are under way and are using rosuvastatin 10 mg.

The Italian GISSI-HF study will assess whether rosuvastatin treatment improves morbidity and mortality in patients with heart failure of any etiology. CORONA includes 4950 patients with heart failure of ischemic etiology class NYHA 2 to 4 who are being randomized to rosuvastatin 10 mg once daily or placebo. The primary outcome is a composite of cardiovascular death or nonfatal MI or stroke.



Related links

1. [HeartWire > News; Dec 2, 2003]

2. [HeartWire > News; Jul 28, 2003]

3. [HeartWire > News; Sep 26, 2002]


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