Sex and the patient with cardiovascular risk factors: focus on sildenafil

Erectile dysfunction (ED) is common in men with cardiovascular disease. The introduction of sildenafil citrate, the first oral agent for the treatment of this disorder, has increased awareness about the risks of sexual activity in cardiac patients and raised concerns about the safety of sildenafil in patients being treated for coronary disease. Sildenafil is a potent and selective inhibitor of phosphodiesterase type 5 (PDE5), the enzyme responsible for the degradation of cyclic guanosine monophosphate (cGMP). Sildenafil acts along the same general pathway as nitric oxide donors to increase cGMP levels and enhance erections. Sildenafil is a modest vasodilator that causes small decreases in systemic arterial pressure and mild preload and afterload reductions. It does not cause major decreases in blood pressure when administered with one or more standard antihypertensive agents. Because PDE5 is also present in small amounts in the systemic vasculature, sildenafil can cause a synergistic and major decrease in pressure when combined with organic nitrates. Use of organic nitrates is the only contraindication to sildenafil use. Data on sildenafil in patients with recent (less than 6 months) myocardial infarction (MI), unstable angina, stroke, and recent life-threatening arrhythmias are not available, so the drug should be used with caution in patients with unstable cardiac conditions. Placebo-controlled and open-label phase 2/3 trials including men with ischemic heart disease did not show an increase in MI or serious cardiovascular events in patients treated with sildenafil versus placebo. None of the serious cardiovascular events reported in these trials were considered treatment related by the investigators. There is a small but finite increased risk of developing ischemia or infarction with sexual activity. Therefore, before prescribing sildenafil or any current or future treatment for ED to patients with known cardiac disease or multiple cardiovascular risk factors, physicians should discuss the potential cardiac risk of sexual activity and perform a complete medical assessment, including an exercise stress test if appropriate.