ANGIOTENSIN-CONVERTING ENZYME-INHIBITORS IN HEART-FAILURE - BLOOD-PRESSURE CHANGES AFTER THE 1ST DOSE

Angiotensin-converting enzyme (ACE) inhibitors prevent the formation o f angiotensin II in the circulation and a range of tissues. ACE inhibi tors not only are effective, well-tolerated antihypertensive drugs but also improve symptoms and signs in patients with congestive cardiac f ailure. In addition, they improve long-term survival in these latter p atients. Although ACE inhibitors are relatively free of side effects i n patients with heart failure, hypotension after the first dose has be en reported that may lead to symptomatic renal, cardiac, or cerebral h ypoperfusion. Most reports have been uncontrolled and anecdotal. We re port a double-blind placebo-controlled study in a parallel group of pa tients with cardiac failure (New York Heart Association classes II thr ough IV). In total, 72 patients (6 groups of 12) were studied after ei ther placebo, captopril, 6.25 mg, enalapril, 2.5, or perindopril, 2 mg orally, enalaprilat 1.5 mg, or perindoprilat, 1.0 mg intravenously. T he blood pressure responses differed between the groups, with a short- lived early fall after captopril and a long-lasting fall after enalapr il, whereas perindopril was no different from placebo. There was no si gnificant difference between the two active intravenous regimens. Plas ma ACE measurements suggested that the relative doses used were at lea st comparable. Further studies are in progress to investigate the mech anisms underlying the differential hemodynamic responses and also to e xplore the clinical relevance to safety and efficacy in the management of heart failure.