SEATTLE — A 12-week study of sildenafil therapy in patients with heart failure due to left ventricular dysfunction and secondary pulmonary hypertension is continuing after an interim analysis found neither therapeutic futility nor overwhelming improvements in exercise capacity, Dr. Gregory Lewis said.
Speaking at the annual meeting of the Heart Failure Society of America, he did not give more specific results on exercise capacity changes in the 28 patients studied so far, but reported improvements in two secondary end points of the trial. In addition, there's no sign so far of any increase in adverse events related to the sildenafil therapy, said Dr. Lewis of Massachusetts General Hospital, Boston, and his associates.
He has no association with the company that makes sildenafil.
The double-blind study randomizes patients with New York Heart Association class III or IV systolic heart failure and secondary pulmonary hypertension to 12 weeks of placebo or oral sildenafil titrated up to 75 mg t.i.d. Twelve of 14 patients per group in the interim analysis completed the protocol.
At week 12, patients in the sildenafil group walked a mean 13% farther on the 6-minute walk test, a significant improvement compared with baseline and compared with the placebo group.
This result is consistent with a mean placebo-corrected 13% increase in the 6-minute walk distance demonstrated in the Sildenafil Citrate Therapy for Pulmonary Arterial Hypertension study, which gave similar doses of sildenafil to patients with idiopathic and other forms of pulmonary arterial hypertension unrelated to left ventricular systolic dysfunction (N. Engl. J. Med. 2005;353:2148–57).
In the current study, five patients in the sildenafil group improved their scores on the Minnesota Living with Heart Failure questionnaire, creating a significant difference in quality-of-life scores between the sildenafil and placebo groups at week 12.
The rates of adverse events did not differ significantly between the groups except in the number of hospitalizations for heart failure, for which there was one in the sildenafil group, and seven in five patients on placebo. The safety of chronic sildenafil therapy has not been studied extensively in this population before.
Dr. Lewis cautioned that the interim analysis rests on small numbers, and that results need to be validated in larger cohorts.
In an earlier study, Dr. Lewis and his associates found that acute administration of a single 50-mg oral dose of sildenafil lowered pulmonary arterial pressures, improved cardiac output, and increased exercise tolerance in patients with systolic heart failure and secondary pulmonary hypertension.