Early administration of ramipril in acute myocardial infarction: neurohormonal and hemodynamic effects and tolerability

Although several large studies indicate a beneficial effect of angiotensin-converting enzyme (ACE) inhibitors after myocardial infarction, the optimal timing of therapy in terms of safety and the effects on neurohormones during myocardial infarction are less well known. In order to investigate the effect of ramipril, administered within 24 h after myocardial infarction, on hemodynamics and neurohormones and its safety, 20 patients with a myocardial infarction were studied. Nine patients had an anterior, 10 an inferior, and 1 a non-Q-wave infarction. Fourteen patients received thrombolytic therapy, whereas 6 did not. The initial dose of ramipril was 1.25 mg, but was gradually increased to 5 mg during the next 4 days. Side effects did not occur. The mean arterial pressure decreased 8 h after the first dose from 84 +/- 2 mm Hg (control) to 77 +/- 2 mm Hg (p < 0.05) and remained decreased thereafter. This was accompanied by a reduction in systemic resistance of 8% after 8 h and of 12% on day 2. Heart rate, cardiac and stroke indexes, and pulmonary artery and wedge pressures did not change. The ACE activity decreased within 1 h of ramipril administration with a maximum of 71% at 4 h after the second dose and remained at this level throughout the study. Angiotensin II decreased by 34% (day 2) and by 41% (day 5). The renin activity gradually increased from 33 +/- 7.5 to 75.4 +/- 11.5 microM/ml on day 5, whereas epinephrine was reduced from day 2 onwards, with a maximal reduction of 71% on day 5. Arginine vasopressin was significantly reduced 5 h after ramipril administration until the end of the study, with a maximum of 77% on day 3. Moreover, a late but significant decrease in norepinephrine occurred on day 5. Thus, oral ramipril results in early ACE inhibition, followed by progressive attenuation of the neuroendocrine activation and a reduction in afterload during the acute phase of myocardial infarction. It is well tolerated, also in combination with nitroglycerin and thrombolytic therapy.