A new study from University Medical Center Gronigen in The Netherlands, released on fast-track by the European Heart Journal, reports that a clinical trial treating pulmonary hypertension patients with sildenafil did not result in reduced pulmonary artery pressure (PAP) or haemodynamic parameters. These patients had preserved ejection fraction (diastolic heart failure) with their pulmonary hypertension, meaning the amount of blood pumped out of the left ventricle of the heart was greater than or equal to 45% (although normal is 55-70%). Although sildenafil was not effective in this cohort of patients, Pfizer has additional clinical trials underway to understand how this medication can help certain individuals with pulmonary hypertension.
“Sildenafil in HFpEF and PH,” or heart failure with preserved ejection fraction and pulmonary hypertension, was a Phase 3 clinical trial that evaluated efficacy of sildenafil by treating patients with sildenafil or placebo and comparing the outcomes of mean PAP and clinical parameters related to exercise capacity. Fifty-two patients were enrolled since October 2011, and each was treated for 12 weeks. During this time, patients were given sildenafil or placebo three times a day for two weeks, and for the remaining time, the amount of medication given was increased and the timing of dosage unchanged.
“Treatment of diastolic left heart failure is a challenging task,” explained the clinical investigators in the trial design. “Compared to systolic left heart failure the level of evidence for known medical treatment regiments is low.” Therefore, the team at Pfizer and researchers at University Medical Centre Groningen was interested in testing sildenafil, which is an inhibitor of phosphodiesterase(PDE)-5, in patients with diastolic left heart failure.
Sildenafil acts as a vasodilator to increase the ease of blood flow through the pulmonary vasculature. However, when the researchers used this therapeutic strategy to treat patients with diastolic left heart failure, they saw no difference between the effects of placebo and sildenafil. Patients’ PAP, cardiac output, and peak VO2 were not significantly different, and adverse events were similar between groups.
“The present single centre, randomized double-blind, and placebo-controlled trial shows that sildenafil does not reduce pulmonary artery pressures in patients with HFpEF with predominantly isolated post-capillary pulmonary hypertension,” stated the researchers in the report of results, written in “Effects of Sildenafil on Invasive Haemodynamics and Exercise Capacity in Heart Failure Patients with Preserved Ejection Fraction and Pulmonary Hypertension: A Randomized Controlled Trial.” “In addition, treatment with sildenafil does not favourably affect other invasive haemodynamics or exercise capacity. Our data therefore do not support the use of sildenafil in these patients.” Instead, sildenafil may be able to act as a treatment for other patients with pulmonary hypertension who are currently being studied in additional clinical trials.