¹Pfizer Inc, New York, NY; Pfizer Inc, Sandwich, United Kingdom

Abstract

The hemodynamic effects of sildenafil have not been assessed in a positively controlled study. The purpose of this study was to determine if the hemodynamic effects of sildenafil lie between that of a nitrate and placebo. Thirty-one subjects with coronary disease and erectile dysfunction received sildenafil 100 mg (n=10), isosorbide mononitrate (ISMN) 40 mg (n=11), or placebo (n=10) about 100 minutes postangiography. Hemodynamic parameters and sildenafil concentrations were measured at baseline, 1, 2, 4, and 6 hours postdose. Subjects receiving sildenafil showed small increases in cardiac index compared with baseline (mean maximum 0.29 L/min/m² at 1 h). Placebo (mean maximum -0.12 L/min/m² at 4 h) and ISMN (mean maximum -0.14 L/min/m² at 1 h) groups initially showed small reductions following dosing. There were small increases in stroke volume index from baseline at each time point postdose in the sildenafil group (mean maximum 4.4 ml/m² at 2 h). Conversely, reductions were seen in both the ISMN (mean maximum -5.8 ml/m² at 1 h) and placebo (mean maximum -2.8 ml/m² at 4 h) groups. Declines in arterial pressure were greatest on ISMN compared with sildenafil (mean maximum -22, -10 mmHg at 2 h, respectively). Sildenafil and ISMN increased heart rate (mean maximum 4, 7 bpm at 1 h, respectively). There were similar reductions in systemic vascular resistance for sildenafil and ISMN. There were consistent and greater reductions in pulmonary vascular resistance in the sildenafil group compared with ISMN and placebo. The mean plasma sildenafil concentration decreased over time with values of 253 ng/ml, 186 ng/ml, 130 ng/ml, and 112 ng/ml at 1, 2, 4, and 6 hours postdose, respectively. During the study, there were no serious adverse events in the sildenafil group, but 1 myocardial infarction occurred in the placebo group. Sildenafil induced smaller changes in central and peripheral hemodynamic pressures compared with ISMN. These hemodynamic changes were well tolerated in both groups.