Effects of early captopril administration on infarct expansion, left ventricular remodeling and exercise capacity after acute myocardial infarction

doi:10.1016/0002-9149(91)90641-W

The American Journal of Cardiology

Volume 68, Issue 8, 15 September 1991, Pages 713-718

https://doi.org/10.1016/0002-9149(91)90641-W Get rights and content

Abstract

In a double-blind study, 99 patients (82 men, age range 40 to 75 years) with acute myocardial infarction (AMI) were randomly assigned to receive captopril or placebo. Treatment began within 24 hours of admission. Serial echocardiographic measurements of endocardial segment lengths and left ventricular (LV) volumes, and ejection fractions were obtained. The 2 groups were matched at baseline except for an excess of previous AMI in the placebo group (13 of 50 vs 2 of 49 patients, p = 0.002). The increase in anterior segment length, from baseline to 2 months, was significantly less in the captopril than in the placebo group (2.8 ± 1.6 vs 10.4 ± 2.4mm, 95% confidence interval [CI] −13.5 to −1.7, p = 0.01). The increase in posterior segment length was also less in the captopril group, but the difference was not significant (3.2 ± 1.2 vs 7.0 ± 1.8mm, 95% CI −8.0 to 0.5, p = 0.08). Fewer patients in the captopril group demonstrated increases in segment length >2 standard deviations of the measurement error (14 of 70 [20%] vs 29 of 72 [40%] patients, p = 0.009). In patients with anterior AMI, the infarct-containing anterior segment length increased by 4.5 ± 2.3 mm in the captopril versus 12.4 ± 3.1 mm in the placebo group (95% CI −15.7 to −0.2, p = 0.046), and fewer patients in the captopril group demonstrated infarct expansion (6 of 20 [30%] vs 13 of 21 [62%] patients, p = 0.04). In patients with inferoposterior AMI, the infarct-containing posterior segment length increased by 3.1 ± 1.6 mm in the captopril versus 9.8 ± 2.4 mm in the placebo group (95% CI −13.3 to −0.1, p = 0.046). No significant treatment effects were seen in LV volumes or maximal exercise performance. This study suggests that early treatment with captopril after AMI can attenuate infarct expansion and favorably influence early LV remodeling.

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Such methodology continues to be the most used in basic research using small animals [59,60]. The introduction of geometrical models in order to get a precise calculation of LV volumes, such as the ellipsoid-truncated, the area-length and, overall, the modified Simpson's rule (Fig. 5) became LV volume calculation with echocardiography as the most popular methodology to study PMI-LVR until our days [61–63]. The end-diastolic volume is a reflection of both structural remodeling and diastolic filling (end-diastolic myocyte fiber length).
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A remarkable medical story: Benefits of angiotensin-converting enzyme inhibitors in cardiac patients
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Angiotensin-converting enzyme inhibitor therapy may benefit patients in the early post-infarction period by yet another mechanism. Infarct expansion (a thinning and dilation of infarcted tissue), which leads to increased mortality, LV chamber enlargement and aneurysm formation, is attenuated when captopril is started less than 24 h after acute MI (77). In experimental rat MI, treatment with ACE inhibitors reduced the extent of infarct expansion when measured two weeks after infarction (78).
The development of angiotensin-converting enzyme inhibitors (ACE inhibitors) has been one of the most remarkable stories in the treatment of cardiovascular diseases. Angiotensin converting enzyme inhibitors have several acute and sustained hemodynamic effects that are beneficial in the presence of left ventricular (LV) dysfunction. They increase cardiac output and stroke volume and reduce systemic vascular resistance as well as pulmonary capillary wedge pressure. The hemodynamic benefits are associated with improvement in the signs and symptoms of congestive heart failure (CHF) as well as decreased mortality, regardless of the severity of CHF. In patients with asymptomatic LV dysfunction, therapy with ACE inhibitors prevented the development of CHF and reduced hospitalization and cardiovascular death. They also increase survival when administered early after an acute myocardial infarction (MI). Most recently, ACE inhibition was associated with improved clinical outcomes in a broad spectrum of high-risk patients with preserved LV function. The mechanism of ACE inhibitors benefits is multifactorial and includes prevention of progressive LV remodeling, prevention of sudden death and arrhythmogenicity and structural stability of the atherosclerotic process. Evidence suggests that ACE inhibitors are underutilized in patients with cardiovascular diseases. Efforts should be directed to prescribe ACE inhibitors to appropriate patients in target doses. It is reasonable to believe that ACE inhibitors have a class effect in the management of LV dysfunction with or without CHF and acute MI. Whether the same is true for ACE inhibitors in the prevention of ischemic events is not known yet.
Effect of very early angiotensin-converting enzyme inhibition on left ventricular dilation after myocardial infarction in patients receiving thrombolysis: Results of a meta-analysis of 845 patients
2000, Journal of the American College of Cardiology
Citation Excerpt :
The first evidence of attenuation of LV dilation produced by ACE inhibition as compared with placebo was obtained from experimental studies of occluded arteries (12). Some small echocardiographic studies showed large effects of ACE inhibition on LV dilation, but they were conducted in patients who did not receive thrombolytic therapy (13–16). In the most frequently cited clinical echocardiographic study showing a beneficial effect of ACE inhibition on LV dilation, only 17% of the patients underwent percutaneous transluminal coronary angioplasty or thrombolytic therapy (4).
OBJECTIVES
We sought to investigate the effect of angiotensin-converting enzyme (ACE) inhibition <9 h after myocardial infarction (MI) on left ventricular (LV) dilation in patients receiving thrombolysis.
BACKGROUND
The ACE inhibitors reduce mortality after MI. Attenuation of LV dilation has been suggested as an important mechanism.
METHODS
The data of 845 patients with three-month echocardiographic follow-up after MI were combined from three randomized, double-blind, placebo-controlled studies. The criteria for these studies included: 1) thrombolytic therapy; 2) ACE inhibition within 6 to 9 h; and 3) evaluation of LV dilation as the primary objective.
RESULTS
The ACE inhibitor was started 3.2 ± 1.7 h after the patients’ first (mainly, 85%) anterior MI. After three months, LV dilation was not significantly attenuated by very early treatment with an ACE inhibitor. The diastolic volume index was attenuated by 0.5 ml/m² (95% confidence interval [CI] −1.5 to 2.5, p = 0.61), and the systolic volume index by 0.5 ml/m² (95% CI −1.0 to 1.9, p = 0.50). Subgroup analysis demonstrated that LV dilation was significantly attenuated by ACE inhibitor treatment for patients in whom reperfusion failed. In contrast, LV dilation was almost unaffected by ACE inhibitor treatment in successfully reperfused patients.
CONCLUSIONS
We could not demonstrate attenuation of LV dilation in patients receiving thrombolysis by ACE inhibitor treatment within 6 to 9 h after MI. We speculate that very early treatment with an ACE inhibitor has a beneficial effect on LV remodeling only in patients in whom reperfusion failed. Other mechanisms may be responsible for the beneficial effects of ACE inhibitors in successfully reperfused patients after MI.
Effect of angiotensin converting enzyme inhibition on sudden cardiac death in patients following acute myocardial infarction: A meta-analysis of randomized clinical trials
1999, Journal of the American College of Cardiology
OBJECTIVES
Estimate the effect of angiotensin converting enzyme (ACE) inhibitors on the risk of sudden cardiac death (SCD) following myocardial infarction (MI).
BACKGROUND
Trials in post-MI patients have shown that ACE inhibitor therapy reduces mortality. However, the effect on SCD as a mechanism has not been clarified.
METHODS
Trials of ACE inhibitor therapy following MI reported between January, 1978 and August, 1997 were identified. Studies were included if they met the following criteria: 1) randomized comparison of ACE inhibitor to placebo within 14 days of MI; 2) study duration/blinded follow-up of ≥6 weeks; 3) the number of deaths and modes of death were reported or could be obtained from the investigators.
RESULTS
We identified 374 candidate articles, of which 15 met the inclusion criteria. The 15 trials included 15,104 patients, 2,356 of whom died. Most (87%) fatalities were cardiovascular and 900 were SCDs. A significant reduction in SCD risk or a trend towards this was observed in all of the larger (N > 500) trials. Overall, ACE inhibitor therapy resulted in significant reductions in risk of death (random effects odds ratio [OR] = 0.83; 95% confidence interval [CI] 0.71–0.97), cardiovascular death (OR = 0.82; 95% CI 0.69–0.97) and SCD (OR = 0.80; 95% CI 0.70–0.92).
CONCLUSIONS
This analysis is consistent with prior reports showing that ACE inhibitors decrease the risk of death following a recent MI by reducing cardiovascular mortality. Moreover, this analysis suggests that a reduction in SCD risk with ACE inhibitors is an important component of this survival benefit.
Effects of early captopril administration after thrombolysis on regional wall motion in relation to infarct artery blood flow
1999, Journal of the American College of Cardiology
Objectives. To determine whether early administration of captopril lessens infarct zone regional wall motion abnormalities when infarct artery blood flow is abnormal.
Background. The interaction between angiotensin-converting enzyme (ACE) inhibitor therapy, ventricular function and infarct artery blood flow has not been well described.
Methods. A total of 493 patients aged ≤75 years with first infarctions, presenting within 4 h of symptom onset, were randomized to receive 6.25 mg captopril, increasing to 50 mg t.d.s. or a matching placebo 2.1 ± 0.4 h after commencing intravenous streptokinase (1.5 × 10⁶U over 30 to 60 min). Trial therapy was stopped 48 h prior to angiography at 3 weeks, to determine regional wall motion and infarct artery flow.
Results. There were no differences in ejection fractions or end-systolic volumes between patients randomized to receive captopril and those randomized to receive a placebo. Among patients with anterior infarction (n = 216), randomization to captopril resulted in fewer hypokinetic chords (40 ± 13; vs. 44 ± 13; p = 0.028) and a trend toward fewer chords >2 SD below normal (26 ± 17 vs. 30 ± 17; p = 0.052) in the infarct zone. In patients randomized to receive captopril who had anterior infarction and Thrombolysis in Myocardial Infarction (TIMI) 0–2, flow there were fewer hypokinetic chords (44 ± 12 vs. 50 ± 9; p = 0.043) and a trend toward fewer chords >2 SD below normal (33 ± 15 vs. 39 ± 13; p = 0.057). Patients receiving captopril who had anterior infarction and corrected TIMI frame counts >27 had fewer hypokinetic chords (42 ± 13 vs. 46 ± 12; p = 0.015) and fewer chords >2 SD below normal (27 ± 17 vs. 32 ± 17; p = 0.047). Captopril had no effect in patients with inferior infarction. There were 20 late cardiac deaths (median follow-up 4 years) in the captopril group and 35 in the placebo group (p = 0.036).
Conclusions. Randomization to receive captopril 2 h after streptokinase improved regional wall motion at 3 weeks. The greatest benefit was seen in patients with anterior infarction particularly when infarct artery blood flow is reduced.

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^☆: This study was supported by a grant from Bristol-Myers Squibb, Princeton, New Jersey.

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Effects of early captopril administration on infarct expansion, left ventricular remodeling and exercise capacity after acute myocardial infarction☆

Abstract

J Am Coll Cardiol

Am J Cardiol

Am J Cardiol

J Am Coll Cardiol

Lancet

Am J Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

Regional cardiac dilatation after acute myocardial infarction

N Engl J Med

Geometric and muscle physiological determinants of cardiac stroke volume as evaluated on the basis of model calculations

Basic Res Cardiol

Wall stress and patterns of hypertrophy in the human left ventricle

J Clin Invest

Ventricular enlargement and reduced survival after myocardial infarction

Circulation

Expansion of transmural myocardial infarction: a pathophysiologic factor in cardiac rupture

Circulation