March 20, 2013
Erectile Dysfunction Drug Fails to Improve Function in
Heart Failure Patients

Rochester, MN—Despite the conjecture that drugs commonly used for erectile dysfunction could have a positive effect on some patients with heart failure, taking sildenafil, marketed as Viagra, did not significantly improve their clinical status or exercise capacity in a recently published study.

The study found that, for patients with heart failure with preserved ejection fraction, those factors were not improved with administration of sildenafil for 24 weeks, compared to placebo. It was published in the Journal of the American Medical Association to coincide with a presentation at the American College of Cardiology's annual Scientific Sessions.

Past studies have suggested that phosphodiesterase-5 inhibitors can improve cardiovascular function.

“Clinical trials of renin-angiotensin system antagonists have not demonstrated improvement in outcomes or clinical status in HFPEF [heart failure with preserved ejection fraction], and effective therapies are needed,” according to background information in the article. “Preclinical studies suggest that inhibition of phosphodiesterase-5 (PDE-5) reverses adverse cardiac structural and functional remodeling and enhances vascular, neuroendocrine, and renal function. In clinical studies, PDE-5 inhibitor therapy improved exercise tolerance and clinical status in patients with idiopathic pulmonary arterial hypertension and in patients with heart failure and reduced ejection fraction.”

A multicenter, randomized clinical trial, conducted by Margaret M. Redfield, MD, of the Mayo Clinic, Rochester, Minnesota, and colleagues, included 216 stable outpatients with heart failure, reduced exercise capacity, and other specific criteria. Most, 52%, of the participants were male, and the median age was 69 years.

Patients were randomized from October 2008 through February 2012 at 26 centers in North America; 113 received sildenafil orally at 20 mg three times daily for 12 weeks followed by 60 mg three times daily for 12 weeks, while another 103 were given a placebo on that schedule. Participants were followed through August 2012.

Peak oxygen consumption after 24 weeks of therapy was the primary endpoint of the study, with secondary end points including change in 6-minute walk distance and a hierarchical composite clinical status score based on time to death, time to cardiovascular or cardiorenal hospitalization, and change in quality of life for participants without cardiovascular or cardiorenal hospitalization at 24 weeks.

At 24 weeks, however, the median change in peak oxygen consumption from the beginning of the study was not significantly different in patients treated with placebo compared to patients treated with sildenafil, according to researchers. No significant differences also were detected in the clinical rank score, the 6-minute walk distance at 24 weeks, or the peak oxygen consumption or 6-minute walk distance at 12 weeks between treatment groups.

“To our knowledge, [this] trial is the first multicenter study to investigate the effect of PDE-5 inhibition in HFPEF,” the authors write. “Contrary to our hypothesis, long-term PDE-5 inhibition in HFPEF had no effect on maximal or submaximal exercise capacity, clinical status, quality of life, left ventricular remodeling, diastolic function parameters, or pulmonary artery systolic pressure.”

In addition, the researchers note, “renal function worsened more and NT-proBNP, endothelin-1, and uric acid levels increased more in patients treated with sildenafil,” adding that patients in the sildenafil group were slightly more likely to withdraw consent, die or become too ill to perform the cardiopulmonary exercise tests. Patients treated with sildenafil also had a higher incidence of vascular adverse events, they point out.

“These findings do not suggest that therapy with the PDE-5 inhibitor sildenafil provides clinical benefit in the general HFPEF population,” the authors conclude.

U.S. Pharmacist Social Connect