Sildenafil promising for stable chronic heart failure

Last Updated: 2007-11-19 17:00:26 -0400 (Reuters Health)

By Megan Rauscher

NEW YORK (Reuters Health) - Long-term use of sildenafil may have a role in the management of heart failure, according to results of a placebo-controlled study published in the November 27 issue of the Journal of the American College of Cardiology.

"Chronic sildenafil appeared to be a remedy based on heart failure pathophysiology and was devoid of remarkable side effects," Dr. Marco Guazzi of the University of Milan, Italy, noted in comments to Reuters Health. "Improvement in exercise ventilation and aerobic efficiency was sustained and was significantly related with an endothelial-mediated attenuation of exercise ergo-ventilatory reflex."

Sildenafil is approved and effective for treating primary pulmonary hypertension, the researcher pointed out. Heart failure leads to secondary pulmonary hypertension, and a defect in endothelial nitric oxide synthesis is typically observed in both pulmonary and systemic arteries of these patients, "providing a rationale for testing sildenafil as a potential new therapeutic strategy."

Dr. Guazzi and colleagues randomly assigned 43 male patients with stable chronic heart failure to placebo or sildenafil (50 mg twice daily) for 6 months, in addition to their current drug therapy.

Compared with placebo, sildenafil reduced systolic pulmonary artery pressure and improved ventilatory efficiency, peak oxygen consumption, breathlessness, flow-mediated vasodilation in the brachial artery, as well as the ergoreflex effect on ventilation, the study team found.

"All changes were significant at p < 0.01," they report.

Aside from flushing, experienced by three patients, no adverse effects were observed. In particular, there were no hyperkinetic arrhythmias, no visual abnormalities, and "no patients developed initial dose hypotension or headache or showed sexual disturbances."

In an accompanying editorial, Dr. Steven R. Goldsmith of University of Minnesota, Minneapolis, praises the study team for their "creative and well-conducted" study. He cautions, however, that "important mechanistic questions that are not yet resolved" need to be, before further studies are conducted. "We have learned, painfully and repeatedly, that inotropic intervention in heart failure, including that based on PDE5 inhibition, is dangerous."

J Am Coll Cardiol 2007;50:2136-2146.