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Early treatment with captopril after acute myocardial infarction
1Department of Cardiology, Western and Royal Infirmary, Glasgow.
Insights
Early treatment with captopril after acute myocardial infarction significantly reduces left ventricular dilatation by altering cardiac structure. However, it does not improve exercise capacity and is not associated with hypotension or significant changes in other neurohormones.
Area of Science:
- Cardiology
- Pharmacology
- Cardiovascular Research
Background:
- Acute myocardial infarction (AMI) can lead to left ventricular (LV) dilatation and impaired cardiac function.
- Early intervention strategies aim to mitigate post-MI adverse remodeling and improve clinical outcomes.
Purpose of the Study:
- To evaluate the effects of early captopril treatment on hemodynamic function, neuroendocrine markers, LV structure, clinical outcomes, and exercise capacity over one year following AMI.
- To assess the impact of captopril on preventing LV dilatation and understand the mechanism behind any observed structural changes.
Main Methods:
- A randomized, double-blind, placebo-controlled trial involving 99 hemodynamically stable patients post-AMI at risk for LV dilatation.
- Patients received either captopril or placebo starting 6-24 hours after symptom onset and continued for 12 months.
- Evaluations included acute hemodynamic effects, serial neuroendocrine biochemistry, echocardiographic measures of LV size, clinical events, and exercise capacity.
Main Results:
- Captopril acutely reduced pulmonary artery pressure and systemic vascular resistance without causing significant hypotension.
- The treatment suppressed the rise in angiotensin II post-MI but did not affect atrial natriuretic factor, arginine vasopressin, or catecholamines.
- After one year, captopril significantly reduced LV end-systolic and end-diastolic volume indices compared to placebo, indicating prevention of dilatation.
- Withdrawal of captopril for one month did not alter LV volumes, suggesting a structural modification rather than a transient hemodynamic effect.
- No significant differences were observed in ventricular arrhythmias or aerobic exercise capacity between the groups.
Conclusions:
- Early initiation of captopril post-AMI effectively suppresses the renin-angiotensin system and significantly decreases left ventricular dilatation.
- The observed reduction in LV dilatation is attributed to an alteration in cardiac structure, not a short-lived hemodynamic effect.
- Long-term captopril treatment in this context does not enhance aerobic exercise capacity.
- Captopril is a safe early treatment option post-MI, with no significant hypotension observed.
Objectives:
To determine the effects of early treatment with captopril on haemodynamic function, neuroendocrine biochemistry, left ventricular structure, clinical outcome, and exercise capacity over one year from acute myocardial infarction.
Design:
Randomised, double blind, placebo controlled comparison of captopril and placebo.
Setting:
Coronary care units and cardiology departments of two university teaching hospitals in Glasgow.
Patients:
99 haemodynamically stable patients with acute myocardial infarction, selected on clinical grounds as being at risk of late ventricular dilatation.
Intervention:
Captopril or identical placebo started between six and 24 hours after start of symptoms and continued for 12 months. Target maintenance dose was 25 mg three times a day.
Main Outcome Measures:
(a) Acute haemodynamic effects of treatment; (b) neuroendocrine biochemistry from admission to two months; and (c) change in echocardiographic measures of left ventricular size, clinical outcome, and exercise capacity after 12 months of treatment with a separate analysis of the effects of one month of treatment withdrawal on left ventricular volumes.
Results:
Captopril caused acute reductions in mean (SEM) pulmonary artery pressure (2.48 (0.69) mm Hg) and systemic vascular resistance (260 (103)) dyn.s.cm-5). Over the first 10 hours captopril reduced mean arterial pressure by 12.1 (2.4) mm Hg compared with 3.8 (1.9) mm Hg in the placebo group. No patient had to be withdrawn from the captopril group because of hypotension. From day 1 onwards systolic and diastolic arterial pressures in the captopril treated group were slightly but not significantly lower than on placebo. There was no difference in the incidence of ventricular or supraventricular arrhythmia with treatment. Captopril prevented the day 3 peak in angiotensin II that occurred in the placebo group (peak concentration (interquartile range): 10.1 (4.8-19.4) pg/ml v 16.8 (4.3-46.3) pg/ml)) but had no effect on atrial natriuretic factor, arginine vasopressin, or catecholamines. Plasma atrial natriuretic factor remained above normal in both groups at two months after infarction. After one year left ventricular volume indices had increased less on captopril than on placebo: left ventricular end systolic volume index 5.4 ml/m2 v 14.7 ml/m2 (95% confidence interval (95% CI) of difference -14.6 to -3.9; p = 0.0011); left ventricular end diastolic volume index 8.4 ml/m2 v 19.0 ml/m2 (95% CI of difference, -17.0 to -4.2; p = 0.0016). Withdrawal of captopril for one month did not affect ventricular volumes. There was no difference in exercise capacity.
Conclusions:
Captopril started between six and 24 hours after acute myocardial infarction is not associated with significant hypotension. It suppresses activation of the renin angiotensin system but has no effect on plasma concentrations of other neurohormones. Atrial natriuretic factor remains raised at two months after myocardial infarction. Captopril significantly decreases left ventricular dilatation. This effect is not lost after one month of treatment withdrawal and is thus due to an alteration of left ventricular structure and not to a short lived haemodynamic action of captopril. Long-term treatment with captopril does not result in improved aerobic exercise capacity after acute myocardial infarction.