Highly anticipated multicenter trial fails to confirm results of smaller studies
Despite high expectations for a commonly used erectile dysfunction drug to treat patients with diastolic heart failure, no beneficial effects were found in a study presented today at the American College of Cardiology's 62nd Annual Scientific Session.
The RELAX Study is the first multicenter trial to look at the effect of chronic therapy with sildenafil in diastolic heart failure. Sildenafil is a phosphodiesterase-5 (PDE-5) inhibitor, a class of drugs used to treat erectile dysfunction and certain types of pulmonary arterial hypertension. Positive results with sildenafil in smaller studies and animal models provided the impetus for the study. But, compared to the placebo, researchers found no beneficial effect of the drug on the primary endpoint of participants' maximum exercise capacity assessed by peak oxygen consumption nor on secondary endpoints of submaximal exercise capacity (as tested by how far patients could walk in six minutes), clinical status, or cardiovascular structure and function.
"The results of our study were surprising and disappointing," said Margaret Redfield, MD, professor of medicine at the Mayo Clinic in Rochester, Minn., and the study's lead author. "There was a lot of anticipation around this study based on other research, and we were hoping to find something that would help these patients, as there are currently few options for treatment."
While current treatment for diastolic heart failure includes recommendations for weight loss, smoking cessation and controlling blood pressure, there are no medications available specifically for its treatment. Because sildenafil can increase blood supply to the lungs, and in animal studies it improved heart and vascular structure and function, researchers believed the drug would improve heart and lung function for diastolic heart failure patients.
According to Dr. Redfield, while it is possible that factors such as insufficient drug dosage or duration contributed to their results, she thinks this is unlikely based on the outcomes of other studies finding benefits from sildenafil.
It is more likely that, compared to other types of heart failure, the disease process seen in diastolic heart failure is different and does not respond well to this category of drug, she said.
Diastolic heart failure is a type of heart failure in which the heart's lower chambers (the ventricles) become stiff and cannot fully relax and fill between beats. When the heart cannot pump blood effectively, blood can back up into the lungs and the rest of the body, causing heart failure symptoms such as shortness of breath. In the RELAX study, patients with diastolic heart failure were enrolled in nine primary centers that make up the Heart Failure Clinical Research Network as well as 16 associated centers. To meet inclusion criteria, participants had to do a cardiopulmonary exercise test and have heart and blood tests showing that they had severe limitations in exercise capacity and abnormalities in the structure and function of their hearts.