Angiotensin-converting enzyme inhibitors in heart failure: blood pressure changes after the first dose.
Angiotensin-converting enzyme (ACE) inhibitors prevent the formation of angiotensin II in the circulation and a range of tissues. ACE inhibitors not only are effective, well-tolerated antihypertensive drugs but also improve symptoms and signs in patients with congestive cardiac failure. In addition, they improve long-term survival in these latter patients. Although ACE inhibitors are relatively free of side effects in patients with heart failure, hypotension after the first dose has been reported that may lead to symptomatic renal, cardiac, or cerebral hypoperfusion. Most reports have been uncontrolled and anecdotal. We report a double-blind placebo-controlled study in a parallel group of patients with cardiac failure (New York Heart Association classes II through IV). In total, 72 patients (6 groups of 12) were studied after either placebo, captopril, 6.25 mg, enalapril, 2.5, or perindopril, 2 mg orally, enalaprilat 1.5 mg, or perindoprilat, 1.0 mg intravenously. The blood pressure responses differed between the groups, with a short-lived early fall after captopril and a long-lasting fall after enalapril, whereas perindopril was no different from placebo. There was no significant difference between the two active intravenous regimens. Plasma ACE measurements suggested that the relative doses used were at least comparable. Further studies are in progress to investigate the mechanisms underlying the differential hemodynamic responses and also to explore the clinical relevance to safety and efficacy in the management of heart failure.
Department of Medicine and Therapeutics, Gardiner Institute, University of Glasgow, Scotland.
J L
JL
Reid
R J
RJ
MacFadyen
I B
IB
Squire
K R
KR
Lees
D000110:Acetylcholinesterase / Q000097:blood; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects*; D002216:Captopril / Q000627:therapeutic use; D004311:Double-Blind Method; D004656:Enalapril / Q000627:therapeutic use; D015773:Enalaprilat / Q000627:therapeutic use; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D007211:Indoles / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D020913:Perindopril
D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; C053500:perindoprilat; D004656:Enalapril; D002216:Captopril; D000110:Acetylcholinesterase; D015773:Enalaprilat; D020913:Perindopril