Cardiovascular Effects of the 3 Phosphodiesterase-5 Inhibitors Approved for the Treatment of Erectile Dysfunction

Received May 17, 2004; revision received June 22, 2004; accepted June 22, 2004. Within the last year, 2 new phosphodiesterase-5 (PDE5) inhibitors have been approved by the US Food and Drug Administration (FDA) for the treatment of erectile dysfunction (ED). Currently, sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis) are on the market. These agents have been shown to be effective in a broad population of men with ED, including patients with vascular disease, coronary artery disease, hypertension, and diabetes.1–5 Because the enzyme that they inhibit, PDE-5, is found in smooth muscle cells of the systemic arteries and veins throughout the body, these agents have mild vasodilator effects and thus, have the potential to impact the cardiovascular system.6 This fact is especially important for the patient with ED, because risk factors for ED include many of the same risk factors that are associated with coronary artery disease: lipid abnormalities, hypertension, smoking, diabetes, and lack of physical exercise.7,8 Because erection is a vascular event, endothelial dysfunction may inhibit it.9 Endothelial dysfunction, an early component of atherosclerosis, is rarely confined to the arteries supplying blood to the penis but more likely occurs throughout the vascular bed. Kaiser et al10 studied 30 men with ED and observed that brachial artery flow–mediated vasodilation and nitroglycerin-mediated vasodilation were reduced in these patients compared with men without ED. Thus, ED may be an early marker of vascular disease.10 Patients with frank coronary artery disease, known to be associated with endothelial dysfunction, and frank atherosclerosis often have ED, as we recently observed in 1 study, in which three fourths of the men with chronic stable angina also reported some degree of ED.11 Hence, the vasodilator effect of these PDE5 agents should be taken into consideration for the cardiac patient, both as …