麻豆传媒

SAN FRANCISCO – Treatment of heart failure patients with preserved ejection fraction with the phosphodiesterase-5 inhibitor sildenafil (Viagra) failed to show any benefit.

Reduction in peak VO_2, which was the primary endpoint, was 0.2 ml/kg/min in both the sildenafil and placebo groups (P=0.98), Margaret Redfield, MD, professor of medicine at the Mayo Medical School, Rochester, Minn., reported at the American College of Cardiology meeting here.

The secondary endpoint results followed the same pattern:

• The change in the 6-minute walk showed that placebo patients increased about 20 meters while the sildenafil patients increased about 5 meters after the 24-week study (P=0.92).
• Mean clinical rank scores for both placebo and sildenafil patients hovered right at the 95 anchor value (P=0.85).

Redfield said the researchers theorized that sildenafil would improve exercise capacity through its ability to increase blood flow to the periphery.

"There was really a strong rationale from existing studies to use sildenafil in heart failure," Redfield explained. "This was a small, placebo controlled, double-blind trial in 216 patients. This was a proof of concept trial with the idea of obtaining a signal that it would be worthwhile to study this in a bigger population.

"However, we did not see any signal of benefit."

William Abraham, MD, professor of medicine at The Ohio State University Columbus, told 麻豆传媒 that the "results of the RELAX trial are disappointing. We have been looking for a silver bullet to treat patients with heart failure and preserved left ventricular ejection fraction. Great promise was seen for phosphodiesterase-5 inhibitors but it didn't pan out in this study. Possibly in a subset of patients with heart failure and pulmonary arterial hypertension these agents may be beneficial.

"An erectile dysfunction drug such as sildenafil has a variety of actions which might be beneficial in the setting of heart failure," Abraham added. "Preliminary data also demonstrated some improvement in patients with reduced ejection fraction heart failure so the RELAX trial was undertaken to evaluate patients with preserved ejection fractions in heart failure."

Abraham said the study "was very well done" but since the results "demonstrated absolutely no benefit," it was doubtful that more research would identify a role for the drug in this population.

"On the other hand," he said, "there are good preliminary data suggesting benefit in reduced ejection fraction heart failure and that should be pursued."

Redfield said that the National Institutes of Health was sponsoring another trial with sildenafil that will explore whether heart failure patients with reduced ejection fractions may benefit from the use of the drug.

RELAX investigators randomly assigned 216 patients with an average LVEF of 60% to placebo or sildenafil 20 mg three times a day for 12 weeks and then were given a dose of 60 mg of sildenafil or placebo through 24 weeks. Among the tests that the participants performed were those to measure exercise capacity, 6-minute walk distance, echo-Doppler scans, quality of life questionnaires, and biomarker studies.

There were three deaths in the sildenafil group compared with none in the placebo group, but the difference was not statistically significant, Redfield explained.

Cardiovascular or cardiorenal hospitalizations were 13% in each group. Adverse events were experienced by 76% of the placebo patients and 80% of the sildenafil patients; serious adverse events occurred in 16% of the placebo patients and 22% of the sildenafil patients.

About 16% of the sildenafil patients withdrew from the study or were unable to complete the 24-week trial compared with 8% of the placebo patients.

None of these differences were statistically significant, she said.

The patients in the study were about 68 years old; the group was evenly divided by sex – although there were more men in the placebo arms and more women in the sildenafil arm.

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