RELAX Study: No Significant Benefit of PDE-5 Inhibitors Observed in Heart Failure

SAN FRANCISCO, CA—Administration of an erectile dysfunction medication provided no beneficial effects in diastolic heart failure patients as stated by Margaret Redfield, MD from the Mayo Clinic in Rochester, MN.

The role of phosphodiasterase type-5 (PDE-5) inhibitors in heart failure with reduced (HFrEF) or preserved (HFpEF) ejection fraction is unclear. Currently PDE-5 inhibitors are approved for erectile dysfunction and Group I pulmonary arterial hypertension.  Small clinical studies have shown that sildenafil improved maximal exercise capacity in HFrEF patients and improved hemodynamics, lung function, RV function, and LV remodeling in HFpEF, PAH, and RV dysfunction patients.

Dr. Redfield and colleagues investigated if the chronic use of sildenafil for 24 weeks compared to placebo would improve exercise capacity (peak VO2) and clinical status in HFpEF patients as presented at ACC.13, the American College of Cardiology's 62nd Annual Scientific Session.

The RELAX study is one of the first double-blinded, placebo-controlled, randomized trials in patients with diastolic heart failure assessing the use of chronic sildenafil therapy. Patients with NYHA class II–IV symptoms, ejection fraction ≥50%, elevated (>400pg/ml) NT-proBNP or elevated rest or exercise filling pressures (catheterization) and peak VO2 ≤60% predicted with respiratory exchange ratio ≥1 on screening cardiopulmonary exercise test were enrolled. A total of 216 participants were randomized 1:1 to either sildenafil 20mg or placebo 20mg, three times daily for 12 weeks, followed by an increased dose 60mg, three times daily for another 12 weeks.

The primary endpoint for this was study was a change in peak VO2 after 24 weeks of therapy. Secondary endpoints were a change in 6-minute walk distance (6MWD) after 24 weeks of therapy and hierarchical composite clinical rank score. Investigators also analyzed change in biomarkers and changes in CV structure and function at 24 weeks using an Echo-Doppler and cardiac magnetic resonance imaging.

Results demonstrated that there was a 91% and 80% (P=0.90) change in peak VO2 for the sildenafil group (n=91) and placebo group (n=94), respectively. Eighty percent of patients in the sildenafil group and 76% in the placebo group experienced adverse events. Serious events were observed in 22% for the sildenafil arm and 16% for the placebo arm.

Chronic sildenafil use in heart failure with preserved ejection fraction was not beneficial in this patient population. Dr. Redfield comments, “Continued efforts to identify novel therapeutic targets in HFpEF are needed.”