Angiotensin-converting enzyme inhibitors in preventing remodeling and development of heart failure after acute myocardial infarction: results of the German multicenter study of the effects of captopril on cardiopulmonary exercise parameters (ECCE).
Early action of angiotensin-converting enzyme (ACE) inhibitors after myocardial infarction (MI) has been shown in large scale clinical trials to reduce mortality over the first weeks. However, the mechanisms involved are yet unclear and several trials showed a tendency toward a small, albeit unexpected, rise in cardiogenic shock or mortality. Since cardiopulmonary exercise testing (CPX) has become a "gold standard" in assessing the severity of heart failure, we studied--after finishing a pilot trial--the effect of captopril versus placebo in 208 patients who were individually titrated (titrated dose, mean 46/69 mg/day after 7 days/4 weeks, respectively) in order to preserve their blood pressure in the acute phase of myocardial infarction; we followed the development of congestive heart failure (CHF) over 4 weeks by measuring oxygen consumption. After 4 weeks, overall oxygen consumption at the anaerobic threshold (VO2-AT; 13.7 vs 13.1), maximal oxygen consumption (VO2max 19.3 vs 18.9 mL/kg per min) and exercise duration (896 vs 839 sec) showed a nonsignificant difference in favor of the captopril group. The predefined, categorized, combined endpoint of severe heart failure or death (heart failure necessitating ACE inhibition, VO2max < 10 mL/kg per min, or death) was significantly reduced in the captopril group (n = 7/104) versus placebo (n = 18/104; p = 0.03). Differences were mainly caused by fewer CHF events (delta n = 10). We conclude that ACE inhibition with individualized dose titration markedly reduces the 4-week incidence of severe heart failure or death; > 10 patients per 100 treated gained major benefits from this therapy.
Kleber
F X
FX
Universitätsklinikum Charité, Humboldt University, Berlin, Germany.
Sabin
G V
GV
Winter
U J
UJ
Reindl
I
I
Beil
S
S
Wenzel
M
M
Fischer
M
M
Doering
W
W
D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology* / Q000627:therapeutic use; D002245:Carbon Dioxide / Q000378:metabolism; D006332:Cardiomegaly / Q000000981:diagnostic imaging / Q000209:etiology / Q000517:prevention & control*; D004311:Double-Blind Method; D004452:Echocardiography; D005080:Exercise Test; D005260:Female; D005858:Germany; D006333:Heart Failure / Q000209:etiology / Q000517:prevention & control*; D006352:Heart Ventricles / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000150:complications* / Q000000981:diagnostic imaging / Q000503:physiopathology; D010101:Oxygen Consumption / Q000187:drug effects; D016896:Treatment Outcome
D000806:Angiotensin-Converting Enzyme Inhibitors; D002245:Carbon Dioxide; D002216:Captopril