Effects of angiotensin-converting enzyme inhibitor alacepril in patients with stable effort angina during chronic isosorbide dinitrate treatment.
Nitrate tolerance has been reported to be reversed by certain types of angiotensin-converting enzyme (ACE) inhibitors. We examined whether alacepril, a new long-acting oral ACE inhibitor, has beneficial effects against exercise-induced angina in patients with stable effort angina after substantial isosorbide dinitrate (ISDN) treatment. Thirteen men with stable effort angina were treated with oral ISDN (80 mg/d) for >3 weeks. After this period, efficacy of single oral administration of either alacepril (50 mg) or its placebo on exercise-induced angina and electrocardiographic changes was examined by treadmill exercise test in a double-blind crossover design. Alacepril significantly improved the exercise duration by 9.1% (p=0.03), the time to 1 mm ST-segment depression by 19% (p<0.01), and the maximal ST-segment depression by 33% (p=0.015) compared with placebo. Alacepril did not significantly alter the rate-pressure product, a marker of myocardial oxygen demand, during exercise test compared with placebo. Plasma renin activity was significantly increased (p<0.05) after administration of alacepril, indicating that alacepril significantly blocked ACE activity in our patients. In conclusion, a single oral administration of the ACE inhibitor alacepril (50mg) elicited beneficial effects against exercise-induced myocardial ischemia in patients with stable effort angina during chronic nitrate treatment. These effects may be mediated by increased coronary blood flow.
Murohara
T
T
Division of Cardiology, Saiseikai Kumamoto Hospital, Kumamoto, Japan.
Tayama
S
S
Tabuchi
T
T
Sumida
H
H
Honda
T
T
Hayasaki
K
K
Yasue
H
H
D000368:Aged; D000787:Angina Pectoris / Q000188:drug therapy*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D002216:Captopril / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004361:Drug Tolerance; D005080:Exercise Test; D006801:Humans; D007548:Isosorbide Dinitrate / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000627:therapeutic use*
D000806:Angiotensin-Converting Enzyme Inhibitors; D014665:Vasodilator Agents; D002216:Captopril; D007548:Isosorbide Dinitrate; C046835:alacepril