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 a lacepril, a new long-acting oral ACE inhibitor, has beneficial effects against exercise-induced angina in patients with stable effort angina after sustained isosorbide dinitrate (ISDN) treatment. Thirteen men w ith stable effort angina were treated with oral ISDN (80 mg/d) for >3 weeks. After this period, the efficacy of single oral administration o f either alacepril (50 mg) or its placebo on exercise-induced angina a nd electrocardiographic changes was examined by treadmill exercise tes t 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 d epression by 19% (p<0.01), and the maximal ST-segment depression by 33 % (p=0.015) compared with placebo. Alacepril did not significantly alt er the rate-pressure product, a marker of myocardial oxygen demand, du ring exercise test compared with placebo, Plasma renin activity was si gnificantly increased (p<0.05) after administration of alacepril, indi cating that alacepril significantly blocked ACE activity in our patien ts. In conclusion, a single oral administration of the ACE inhibitor a lacepril (50 mg) elicited beneficial effects against exercise-induced myocardial ischemia in patients with stable effort angina during chron ic nitrate treatment, These effects may be mediated by increased coron ary blood flow.