Sildenafil citrate for treatment of erectile dysfunction has minor side effects caused by vasodilation, including headache, facial flushing, and nasal congestion. Although expert consensus guidelines advise against the use of sildenafil in men with active coronary ischemia, event monitoring data have not shown any increase in adverse cardiac events in randomized trials using sildenafil and placebo.
DeBusk and associates conducted a randomized, double-blind, prospective, multi-center, placebo-controlled study to evaluate the efficacy and safety of sildenafil citrate when used to treat erectile dysfunction. Men in stable sexual relationships with confirmed erectile dysfunction who had stable coronary artery disease (CAD) were included. No nitrates could have been used in the four weeks before the study, and men were required to be at low or intermediate risk for adverse cardiovascular events during sexual activity as determined by the Princeton guidelines. Patients were randomized to receive sildenafil or placebo.
The study drug was started at 50 mg and could be adjusted to 25 or 100 mg, depending on efficacy and tolerability. Outcomes measured for efficacy included questions 3 (frequency of penetration) and 4 (frequency of maintained erections after penetration) of the International Index of Erectile Function. Other lifestyle and efficacy measurements were used with two questionnaires to measure the response of the partners to the intervention.
Among the 142 patients randomized and included in the intent-to-treat analysis of efficacy, patients in the sildenafil group had significantly higher improvement in erections and intercourse rate than those who received placebo. Partner satisfaction also was higher in the treatment group, but the number of respondents was too small to determine significance.
Adverse events were slightly higher in the sildenafil group, as shown by previous trials. Only one patient taking sildenafil developed a cardiac adverse event; this patient had moderate chest pressure and vasodilation on day 9. The study medication was halted for several days and then resumed. This same patient later developed moderate edema of the right forearm and moderate hypertension. No further adverse events were noted when the dosage was reduced to 25 mg. Five patients had increases in angina scores, but these increases occurred almost equally in both groups.
The authors conclude that sildenafil is effective and well tolerated in patients with stable CAD. Although the sildenafil group had a higher rate of adverse events, the rate of events related to cardiovascular effects was low.
editor’s note:The use of phosphodiesterase type 5 inhibitors in the treatment of erectile dysfunction caused early concerns about patients with cardiovascular disease. Many of these concerns have been unfounded. Sexual activity is not associated with a significant absolute increase in morbidity or mortality, and guidelines have been developed to identify the men who may be harmed by resuming an active sex life.1 Among all patients who participated in placebo-controlled trials of sildenafil, the incidence of myocardial infarction was slightly lower among those taking the study medication.
Among all patients enrolled in open-label studies of sildenafil, the incidence of death attributed to cardiovascular disease was the same in the treatment and the placebo groups. Even in patients with stable CAD, previous studies confirm the safety of sildenafil use that was noted by DeBusk and colleagues in this study. In studies examining physiologic measurements in patients with coronary ischemia who were given sildenafil, vardenafil, or tadalafil, total exercise duration increased in men with stable angina. The arrhythmogenic potential of all of the phosphodiesterase type 5 inhibitors is currently determined to be minimal, although vardenafil is specifically contraindicated for concomitant use with class IA and class III antiarrhythmic agents. It appears that with some attention to patient selection, phosphodiesterase type 5 inhibitors can be used safely in the majority of men, even in the presence of stable cardiovascular disease.—r.s.