Sildenafil in patients with cardiovascular disease

Cardiologists are seeing increasing numbers of patients with erectile dysfunction (ED), which frequently coexists with cardiovascular disease. The pharmacologic profile of the new class of phosphodiesterase (PDE) inhibitors-specifically PDE5 inhibitors-and their potential effects on hemodynamic variables have therefore become significant factors in therapeutic decision making. Most of the published data linking PDE5 inhibitor effects and cardiovascular disease relate to sildenafil, although >or=2 new agents are in various stages of development and clinical trials. Sildenafil and other PDE5 inhibitors act on vascular smooth muscle, predominantly in the corpus cavernosum. PDE5 is not found in cardiomyocytes, and no effect of PDE5 inhibition on cardiac contractility has been demonstrated. On the basis of a safety database comprising thousands of men with ED, sildenafil has demonstrated minimal adverse effects in men with stable ischemia, hypertension, and/or severe coronary artery disease. Sildenafil has modest effects on hemodynamic variables and has been shown to increase coronary artery flow reserve. Alone or combined with >or=1 antihypertensive medication, sildenafil did not increase the incidence of adverse events or hypotensive episodes. Sildenafil-associated decreases in systolic and diastolic blood pressure, the result of its vasodilator activity, have been modest. Sildenafil has decreased both elevated pulmonary vascular resistance and elevated pulmonary artery pressures in patients with pulmonary vascular disease. Beneficial changes in hemodynamics have been observed with the use of sildenafil in patients with congestive heart failure with underlying ischemic and other dilated cardiomyopathies. No association between sildenafil and increased cardiovascular morbidity or mortality has emerged in analyses of clinical trial data.