The effect of sildenafil on human vascular function, platelet activation, and myocardial ischemia

OBJECTIVES We studied the effects of sildenafil, a phosphodiesterase 5 inhibitor, on coronary and peripheral vascular function, platelet activation, and myocardial ischemia. BACKGROUND Nitric oxide vasodilates and inhibits platelet activation by generating cyclic guanosine 5'-monophosphate, which is metabolized by phosphodiesterase type 5. METHODS The effect of oral sildenafil on resting coronary vascular tone, endothelium-dependent and -independent function and platelet activation was measured in 24 patients. An additional 24 patients with coronary artery disease (CAD) and ischemia during exercise, and 12 control subjects received either 100 mg of sildenafil, 10 mg of isosorbide dinitrate (ISDN) or placebo during exercise on three separate days in a randomized, double-blind manner. Flow-mediated dilation of the brachial artery was measured, and CAD patients underwent treadmill exercise testing. RESULTS Sildenafil (100 mg) vasodilated epicardial coronary arteries (+6.9 +/- 1.3%, p < 0.0001). Coronary epicardial and microvascular responses with acetylcholine and cold-pressor testing improved, with a greater enhancement in patients with CAD and endothelial dysfunction. Verapamil responses were unchanged. Both resting and adenosine diphosphate-stimulated platelet IIb/IIIa receptor activation was inhibited by sildenafil (p < 0.05). Brachial arteries dilated in response to sildenafil in controls. Peak flow-mediated dilation was similar, but the duration of hyperemia was prolonged after sildenafil administration (p < 0.001). Compared with placebo, ISDN improved myocardial ischemia during exercise (p < 0.05), whereas the effect of sildenafil was intermediate between the two. CONCLUSIONS Sildenafil dilates epicardial coronary arteries, improves endothelial dysfunction and inhibits platelet activation in patients with CAD. It has an intermediate effect on myocardial ischemia compared with ISDN and placebo. (C) 2002 by the American College of Cardiology Foundation.