Cardiovascular effects of sildenafil during exercise in men with known or probable coronary artery disease: a randomized crossover trial.
BACKGROUND
The relationship between sildenafil citrate use and reported adverse cardiovascular events in men with coronary artery disease (CAD) is unclear.


OBJECTIVE
To evaluate the cardiovascular effects of sildenafil during exercise in men with CAD.


METHODS
Randomized, double-blind, placebo-controlled crossover trial conducted March to October 2000 at a US ambulatory-care referral center among 105 men with a mean (SD) age of 66 (9) years who had erectile dysfunction and known or highly suspected CAD.


METHODS
All patients underwent 2 symptom-limited supine bicycle echocardiograms separated by an interval of 1 to 3 days after receiving a single dose of sildenafil (50 or 100 mg) or placebo 1 hour before each exercise test.


METHODS
Hemodynamic effects of sildenafil during exercise (onset, extent, and severity of ischemia) assessed by exercise echocardiography.


RESULTS
Mean (SD) resting ejection fraction was 56% (7%) (range, 39%-68%). After sildenafil use, resting systolic blood pressure was reduced from 135 (19) mm Hg to 128 (17) mm Hg, for a mean change of -7 mm Hg (95% confidence interval [CI], -9 to -4 mm Hg; P<.001). After placebo use, the mean (SD) change was from 135 (20) mm Hg to 133 (19) mm Hg, a difference of -2 mm Hg (95% CI, -6 to 0.3 mm Hg; P =.08). The difference between mean change after sildenafil and placebo use was 4.3 (95% CI, 0.9-7.7; P =.01). Resting heart rate, diastolic blood pressure, and wall motion score index (a measure of the extent and severity of wall motion abnormalities) did not change significantly in either group. Exercise capacity was similar with sildenafil use (mean [SD], 4.5 [1.0] metabolic equivalents) and placebo use (mean [SD], 4.6 [1.0] metabolic equivalents; mean difference, 0.07; 95% CI, -.06 to 0.19; P =.29). Exercise blood pressure and heart rate increments were similar. Dyspnea or angina developed in 69 patients who took sildenafil and 70 patients who took placebo (P =.89); exercise electrocardiography was positive in 12 patients (11%) who took sildenafil and 17 patients (16%) who took placebo (P =.09). Exercise-induced wall motion abnormalities developed in similar numbers of patients after sildenafil and placebo use (84 and 86 patients, respectively; P =.53). Wall motion score index at peak exercise was similar after sildenafil and placebo use (mean [SD], 1.4 [0.4] vs 1.4 [0.4]; mean difference, 0.01; 95% CI, -0.01 to 0.03; P =.40).


CONCLUSIONS
In men with stable CAD, sildenafil had no effect on symptoms, exercise duration, or presence or extent of exercise-induced ischemia, as assessed by exercise echocardiography.
Arruda-Olson
Adelaide M
AM
Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA.
Mahoney
Douglas W
DW
Nehra
Ajay
A
Leckel
Marilyn
M
Pellikka
Patricia A
PA
D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D003324:Coronary Artery Disease / Q000150:complications / Q000503:physiopathology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D025401:Echocardiography, Stress; D004562:Electrocardiography; D007172:Erectile Dysfunction / Q000150:complications / Q000188:drug therapy; D015444:Exercise; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D010879:Piperazines / Q000494:pharmacology* / Q000627:therapeutic use; D011446:Prospective Studies; D011687:Purines; D000068677:Sildenafil Citrate; D013450:Sulfones
D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D000068677:Sildenafil Citrate