The effect of vardenafil, a potent and highly selective phosphodiesterase-5 inhibitor for the treatment of erectile dysfunction, on the cardiovascular response to exercise in patients with coronary artery disease.
OBJECTIVE
The effect of vardenafil, a potent and highly selective phosphodiesterase-5 (PDE5) inhibitor, on symptom-limited exercise time, time to first awareness of angina, and time to ischemic threshold (ST-segment depression > or =1 mm from baseline) during exercise tolerance testing (ETT) was examined in patients with stable coronary artery disease (CAD).


BACKGROUND
Erectile dysfunction (ED) is common among men with CAD. PDE5 inhibition is increasingly the preferred treatment option for ED. However, the effect of PDE5 inhibition on exercise-induced ischemia in CAD patients has received limited prospective evaluation.


METHODS
In this double-blind, crossover, single-dose multicenter study, 41 men with reproducible stable exertional angina due to ischemic CAD received vardenafil 10 mg or placebo, followed by ETT (5 to 10 metabolic equivalents [METS], Bruce protocol) 1 h postdose. Sublingual nitrate use was prohibited for > or =24 h pre- and postexercise study days. End points included symptom-limited treadmill exercise time, time to first awareness of angina, time to ischemic threshold, and safety.


RESULTS
Relative to placebo, vardenafil 10 mg did not alter exercise treadmill time (427 +/- 105 s vs. 433 +/- 109 s, p = 0.39), or time to first awareness of angina (292 +/- 110 s vs. 291 +/- 123 s, p = 0.59), but significantly prolonged time to ischemic threshold (334 +/- 108 s vs. 381 +/- 108, p = 0.0004). At peak exercise, vardenafil 10 mg did not alter blood pressure, heart rate, or rate-pressure product relative to placebo. The most common adverse events (facial flushing and headache) were of mild or moderate intensity, and short-lived.


CONCLUSIONS
Vardenafil 10 mg did not impair the ability of patients with stable CAD to exercise at levels equivalent or greater than that attained during sexual intercourse (average of 2.5 to 3.3 METS).
Thadani
Udho
U
Oklahoma University, Health Sciences Center, and Veterans Affairs Medical Center, Cardiology Section, Oklahoma City, Oklahoma 73104, USA. udho-thadani@ouhsc.edu
Smith
William
W
Nash
Stephen
S
Bittar
Neville
N
Glasser
Stephen
S
Narayan
Puneet
P
Stein
Richard A
RA
Larkin
Sharon
S
Mazzu
Arthur
A
Tota
Robert
R
Pomerantz
Kenneth
K
Sundaresan
Pavur
P
D015106:3',5'-Cyclic-GMP Phosphodiesterases; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002319:Cardiovascular System / Q000187:drug effects* / Q000503:physiopathology*; D003324:Coronary Artery Disease / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*; D018592:Cross-Over Studies; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D003971:Diastole / Q000187:drug effects / Q000502:physiology; D004311:Double-Blind Method; D004562:Electrocardiography; D007172:Erectile Dysfunction / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*; D015444:Exercise / Q000502:physiology*; D005080:Exercise Test; D017079:Exercise Tolerance / Q000187:drug effects / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007093:Imidazoles / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010726:Phosphodiesterase Inhibitors / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010727:Phosphoric Diester Hydrolases / Q000097:blood / Q000187:drug effects* / Q000493:pharmacokinetics; D010879:Piperazines / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013450:Sulfones; D013599:Systole / Q000187:drug effects / Q000502:physiology; D016896:Treatment Outcome; D014227:Triazines; D000069058:Vardenafil Dihydrochloride
D007093:Imidazoles; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D013450:Sulfones; D014227:Triazines; D000069058:Vardenafil Dihydrochloride; D010727:Phosphoric Diester Hydrolases; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; C517381:PDE5A protein, human