title: 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.
abstract: 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).
authors.affiliation: Oklahoma University, Health Sciences Center, and Veterans Affairs Medical Center, Cardiology Section, Oklahoma City, Oklahoma 73104, USA. udho-thadani@ouhsc.edu
authors.forename: Udho
authors.initials: U
authors.lastname: Thadani
authors.forename: William
authors.initials: W
authors.lastname: Smith
authors.forename: Stephen
authors.initials: S
authors.lastname: Nash
authors.forename: Neville
authors.initials: N
authors.lastname: Bittar
authors.forename: Stephen
authors.initials: S
authors.lastname: Glasser
authors.forename: Puneet
authors.initials: P
authors.lastname: Narayan
authors.forename: Richard A
authors.initials: RA
authors.lastname: Stein
authors.forename: Sharon
authors.initials: S
authors.lastname: Larkin
authors.forename: Arthur
authors.initials: A
authors.lastname: Mazzu
authors.forename: Robert
authors.initials: R
authors.lastname: Tota
authors.forename: Kenneth
authors.initials: K
authors.lastname: Pomerantz
authors.forename: Pavur
authors.initials: P
authors.lastname: Sundaresan
mesh_terms: 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
chemical_list: 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