Effects of Captopril on Cardiopulmonary Exercise Parameters (ECCE) - ECCE

Description:

The ECCE was a multicenter, randomized, double-blind, parallel group trial designed to investigate the influence of early inhibition of ACE in patients with acute myocardial infarction (AMI).

Hypothesis:

Early initiation of ACE-inhibitors (captopril) after acute myocardial infarction will be associated with decreased rates of severe heart failure and death.

Study Design

Study Design:

Patients Enrolled: 208

Patient Populations:

All patients had acute myocardial infarction verified by elevation of creatine kinase above 500 units/L and positive ECG findings. Patients were eligible if they were included within 24–72 hours after onset of chest pain.

Exclusions:

Lack of contraindications to ACE inhibition or exercise limitation due to concomitant disease or severe hemodynamic complications of acute myocardial infarction.

Primary Endpoints:

Combined endpoint of death or severe heart failure (defined as heart failure necessitating ACE inhibition, VO2max <10 mL/kg per min) and average oxygen consumption at 4 weeks.

Secondary Endpoints:

Left ventricular EF

Drug/Procedures Used:

Cardiopulmonary exercise testing (CPX) is a "gold standard" in assessing the severity of heart failure. Patients were randomized to captopril (n=104) versus placebo (n=104). The initial dose of medication was administered after 49.5 and 50.1 hours respectively, after onset of chest pain in the captopril and placebo groups. The dose titration was performed by adjustment to individual tolerance and with a strong effort to keep systolic blood pressure >100 mm Hg and diastolic blood pressure >60 mm Hg (titrated dose, mean 46/69 mg/day after 7 days/4 weeks, respectively) in order to preserve the blood pressure in the acute phase of myocardial infarction; development of congestive heart failure (CHF) was followed over 4 weeks by measuring oxygen consumption. Echocardiography and chest-xray were also performed.

Concomitant Medications:

Concomitant medication was left to the decision of the physicians taking primary care of the patients and was carefully monitored.

Principal Findings:

Baseline characteristics were comparable among groups. There were no major differences in infarct size or treatment of AMI, however there was a predominance of anterior MI in the placebo group (n=51 pts for the placebo group and n=36 pts for the captopril group, p = 0.048). The average oxygen consumption after 4 weeks was not significantly different between groups (13.6±4 ml/kg/min for the captopril group, n=102 and 13.1±4 ml/kg/min for the placebo group, n=101), nor was the exercise time (896±613 for the capropril group and 836±329 for the placebo group). The combined endpoint of death, development of overt heart failure necessitating ACE-inhibitor therapy despite maximal therapy and VO2max ≤10 mL/kg per min after 4 weeks, occurred in 7 pts on captopril (6.7%) and 18 pts (17.3%) on placebo; p=0.03. The difference was mainly due to fewer congestive heart failure events (VO2max ≤10, 4 vs 10 patients; CHF necessitating ACE inhibitors, 1 vs 5 pts). Left ventricular volumes were smaller in the captopril group at 4 weeks (ESV, p <0.05) and at 3 months (EDV, p <0.05) than in the placebo group. However, volume changes were small and only of borderline significance. Left ventricular ejection fraction at 4 weeks was 47 ± 11% in the captopril group and 44 ± 13% in the placebo group (p=0.09). Signs or symptoms of acute heart failure during the course of 4 weeks occurred in 31 pts of the captopril group (29.8%) and 40 pts in the placebo group (38.5%; p=NS). There were no significant changes in radiographic heart size or in oxygen consumption at 3 months.

Adverse events with possible, likely, or definite connection to therapy occurred at a similar rate in both groups (36% vs 30% in the captopril and placebo-treated pts, respectively). Severe adverse events were observed with similar frequency in both groups (17.3%) and were mainly caused by heart failure, myocardial ischemia, and arrhythmia. Hypotension with diastolic blood pressure <60 mm Hg occurred in 22% and 11.5% in the captopril and placebo groups, respectively.

Interpretation:

Among patients with acute myocardial infarction, treatment with the ACE inhibitor captopril with individualized dose titration was associated with a reduction in the 4-week incidence of severe heart failure or death.

This study showed a beneficial effect of early, carefully ad individually titrated ACE-inhibition in terms of death and overt heart failure, in contrast to the disappointing results from larger trials (GISS-II, ISIS-IV). Though a major difference between those trials and the ECCE trial was lack of individualized up-titration, it must also be emphasized that in the ECCE trial, the placebo group included a larger percentage of patients with anterior MI.

References:

Kleber FX, et al. 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). AJC 1997;80(3):162A-167A.

Clinical Topics: Heart Failure and Cardiomyopathies, Noninvasive Imaging, Acute Heart Failure, Echocardiography/Ultrasound

Keywords: Myocardial Infarction, Creatine Kinase, X-Rays, Hypotension, Blood Pressure, Electrocardiography, Captopril, Oxygen Consumption, Chest Pain, Heart Failure, Stroke Volume, Echocardiography


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