Long-term ACE-inhibitor therapy in patients with heart failure or left-ventricular dysfunction: a systematic overview of data from individual patients

MD Flather, S Yusuf, L Køber, M Pfeffer, A Hall… - The Lancet, 2000 - thelancet.com
MD Flather, S Yusuf, L Køber, M Pfeffer, A Hall, G Murray, C Torp-Pedersen, S Ball, J Pogue
The Lancet, 2000thelancet.com
Background We undertook a prospective systematic overview based on data from individual
patients from five long-term randomised trials that assessed inhibitors of angiotensin-
converting enzyme (ACE) in patients with left-ventricular dysfunction or heart failure.
Methods Three of the trials enrolled patients within a week after acute myocardial infarction.
Data were combined by use of the Peto-Yusuf method. Findings Overall 12 763 patients
were randomly assigned treatment or placebo and followed up for an average of 35 months …
Background
We undertook a prospective systematic overview based on data from individual patients from five long-term randomised trials that assessed inhibitors of angiotensin-converting enzyme (ACE) in patients with left-ventricular dysfunction or heart failure.
Methods
Three of the trials enrolled patients within a week after acute myocardial infarction. Data were combined by use of the Peto-Yusuf method.
Findings
Overall 12 763 patients were randomly assigned treatment or placebo and followed up for an average of 35 months. In the three post-infarction trials (n=5966), mortality was lower with ACE inhibitors than with placebo (702/2995 [23·4%] vs 866/2971 [29·1%]; odds ratio 0·74 [95% Cl 0·66–0·83]), as were the rates of readmission for heart failure (355 [11·9%] vs 460 [15·5%]; 0·73 [0·63–0·85]), reinfarction (324 [10·8%] vs 391 [13·2%]; 0·80 [0·69-0·94]), or the composite of these events (1049 [35·0%] vs 1244 [41·9%]; 0·75 [0·67–0·83]; all p < 0·001). For all five trials the ACE-inhibitor group had lower rates of death than the placebo group (1467/6391 [23·0%] vs 1710/6372 [26·8%]; 0·80 [0·74–0·87]) and lower rates of reinfarction (571 [8·9%] vs 703 [11·0%]; 0·79 [0·70–0·89]), readmission for heart failure (876 [13-·%] vs 1202 [18·9%]; 0·67 [0·61–0·74]), and the composite of these events (2161 [33·8%] vs 2610 [41·0%]; 0·72 [0·67–0·78]; all p < 0·0001). The benefits were observed early after the start of therapy and persisted long term. The benefits of treatment on all outcomes were independent of age, sex, and baseline use of diuretics, aspirin, and β-blockers. Although there was a trend towards greater reduction in risk of death or readmission for heart failure in patients with lower ejection fractions, benefit was apparent over the range examined.
Interpretation
This systematic overview shows that ACE inhibitors lower rates of mortality, myocardial infarction, and hospital admission for heart failure in patients with left-ventricular dysfunction or heart failure with or without a recent myocardial infarct. The use of ACE inhibitors should be part of routine practice in these patients.
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