Comparison of Enalapril Versus Captopril on Left Ventricular Function and Survival Three Months After Acute myocardial infarction - PRACTICAL


Captopril vs. enalapril for LV function in acute MI.


(1) Administration of angiotensin-converting enzyme (ACE) inhibitors within the first 24 hours after acute MI will attenuate left ventricular (LV) dilation.
(2) Benefits are not confined to patients with reduced LV ejection fraction (EF).
(3) All ACE inhibitors are equally efficacious.
(4) Alternative dosing regimens can improve drug tolerability, yet maintain efficacy.

Study Design

Study Design:

Patients Screened: 523
Patients Enrolled: 225
Mean Follow Up: 12 months
Mean Patient Age: 64
Female: 23

Patient Populations:

Presented within 24 hours of the onset of chest pain considered to be the initial symptom of acute MI
Pain associated with at least 1 of the following features:
Elevation of the ST segment in > 2 contiguous electrocardiographic leads;
New pathologic Q waves; or
Elevation of plasma creatine phosphokinase.


Persistent hypotension with systolic blood pressure < 90 mmHg.
History of sensitivity to ACE inhibitors, or the use of ACE inhibitors within 1 week of the infarction.
Hemodynamically significant valvular stenosis.
Clinically severe renal or hepatic disorders.
Clear indication for treatment with an ACE inhibitor.
Refusal to give informed consent.
Expected to comply poorly with treatment.

Primary Endpoints:

EF and LF volumes as measured by radionuclide ventriculography

Secondary Endpoints:

Total mortality

Drug/Procedures Used:

Oral captopril 6.25 mg at 2-hour intervals for 3 doses, followed by 25 mg 3 times daily started 6 hours after initial dose, continued for 12 months; or
Oral enalapril 1.25 mg at 2-hour intervals for 3 doses, followed by 5 mg 3 times daily started 6 hours after initial dose, continued for 12 months; or
Oral enalapril 1.25 mg at 2-hour intervals for 3 doses, followed by 5 mg 3 times daily started 6 hours after initial dose, continued for 12 months; or
Placebo at matching times, continued for 12 months
Drug was withheld at scheduled times during the first 48 hours if systolic blood pressure was < 90 mg Hg.

Concomitant Medications:

Calcium antagonists

Principal Findings:

The ACE inhibitor group had a significant increase in EF (45 ± 1 to 47 ± 1%; p = 0.005).

The ACE inhibitor group had a significantly attenuated LV dilation compared with those in the placebo group.

168 ± 4 to 172 ± 4 ml in the ACE inhibitor group vs. 175 ± 6 to 189 ± 7 ml in the placebo group; p = 0.051 for LV end-diastolic volume.

94 ± 3 to 94 ± 4 ml in the ACE inhibitor group vs. 99 ± 6 to 108 ± 7 ml in the placebo group; p = 0.026 for LV end-systolic volume.

The beneficial effects of ACE inhibitor therapy on LV function were observed irrespective of the degree of initial LV dysfunction, and were comparable in both the captopril and enalapril groups:
Captopril (n = 55) significantly increased EF by 2% (45 ±6 to 47 ±6%; p = 0.023), whereas in the enalapril group (n = 65) EF increased by 2% (46 ±6 to 48 ±6%) and the change almost achieved statistical significance (p = 0.08). There was no significant difference in these changes between groups (p = 0.66).
End-diastolic volume did not change significantly in either the captopril (171 ±23 to 176 ±24 ml; p = 0.23) or the enalapril (167 ±21 to 168 ±21 ml; p = 0.65) groups, nor was there a statistically significant difference between groups (p = 0.51).
End-systolic volume showed little change in either the captopril (97 ±5 to 98 ±7 ml; p = 0.88) or the enalapril (92 ± 5 to 91 ±5 ml; p = 0.88) groups, nor was there a significant difference between groups (p = 0.75).
Survival at 90 days and at 12 months was significantly improved in the enalapril group:
Deaths at 90 days: 7 placebo, 9 captopril, 1 enalapril; p = 0.038.
deaths at 12 months: 12 placebo, 10 captopril, 2 enalapril; p = 0.022.
There were 16 deaths (7%) from cardiac causes, the majority being mechanical (i.e., LV failure and cardiac rupture; 6 placebo, 4 captopril).
Six deaths were presumably caused by ventricular arrhythmias; 5 were sudden undocumented deaths with no premonitory symptoms (1 placebo, 3 captopril, 1 enalapril) and 1 was from documented ventricular fibrillation).
Twenty-four deaths (11%) from all causes occurred in the 12-month follow-up period (12 placebo, 10 captopril, 2 enalapril).
There were 21 deaths from cardiac causes (12 placebo, 8 captopril, 1 enalapril) of which 12 (8 placebo, 4 captopril) were caused by either LV failure or cardiac rupture.
Nine were sudden, caused by either documented or presumed ventricular arrhythmias (4 placebo, 4 captopril, 1 enalapril).
There were 3 non-cardiac-related deaths; 1 from cerebrovascular accident (captopril), 1 resulting from acute gastrointestinal bleeding (captopril), and 1 from metastatic carcinoma of the bronchus (enalapril).
Kaplan-Meier estimates of survival curves showed a significantly improved survival at 90 days (Mantel-Cox chi-square = 6.52, df = 2; p = 0.038) and at 12 months (Mantel-Cox chi-square = 7.67, df = 2; p = 0.022) in patients treated with enalapril.


Immediate administration of captopril and enalapril improved LV function and prevented LV dilation after acute MI. The benefit was similar with both ACE inhibitors and was in excess of the benefits of optimal conventional therapy. There was a significant reduction in mortality with enalapril.


1. Am J Cardiol 1994;73:1180-6. Final results

Clinical Topics: Arrhythmias and Clinical EP, Heart Failure and Cardiomyopathies, SCD/Ventricular Arrhythmias, Acute Heart Failure

Keywords: Stroke, Kaplan-Meier Estimate, Enalapril, Creatine Kinase, Follow-Up Studies, Pyridinolcarbamate, Ventricular Fibrillation, Blood Pressure, Electrocardiography, Captopril, Chest Pain, Heart Rupture, Heart Failure, Death, Sudden, Cardiac

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