EVIDENCE OF A PARTIAL ESCAPE OF RENIN-ANGIOTENSIN-ALDOSTERONE BLOCKADE IN PATIENTS WITH ACUTE MYOCARDIAL-INFARCTION TREATED WITH ACE INHIBITORS

Angiotensin-converting enzyme (ACE) inhibitors have been designed to block the renin-angiotensin system and can represent an effective therapeutic approach in those settings where such a system is active, such as myocardial infarction. In a randomized placebo-controlled study, 10 patients with acute myocardial infarction allocated to treatment with increasing doses of zofenopril calcium and 10 patients allocated to placebo were studied in hospital, within 24 hours from symptoms, during 11 sampling periods to assess the time course of ACE inhibition and renin-angiotensin-aldosterone blockade. Zofenopril administration was followed by a dose-dependent inhibition of in vitro ACE activity (7.5 mg, 65%; 15 mg, 89%; 30 mg, 94.5%) and a progressive increase in plasma active renin. Conversely, plasma aldosterone decreased during the first 3 days of treatment and then returned toward baseline values, as did blood pressure, despite a persistent inhibition of ACE. The present data suggest the existence of an interesting dissociation between the time-course of ACE inhibition and that of blockade of the renin-angiotensin system in patients with acute myocardial infarction. This discrepancy could arise from the combination of an only partial in vivo ACE inhibition and the compensatory increase in plasma renin that occurs during treatment with ACE inhibitors. A better understanding of this relationship would seem to be useful in addressing the correct use of ACE inhibitors in patients with acute myocardial injury.