Elsevier

American Heart Journal

Volume 152, Issue 3, September 2006, Pages 470-477
American Heart Journal

Clinical Investigation
Acute Ischemic Heart Disease
Effects of early angiotensin-converting enzyme inhibition in patients with non–ST-elevation acute anterior myocardial infarction

https://doi.org/10.1016/j.ahj.2006.02.022Get rights and content

Background

No data are available on the clinical efficacy of the early administration (<24 hours from onset of chest pain) of angiotensin-converting enzyme inhibitors in non-thrombolysed patients with non–ST-elevation myocardial infarction (NSTEMI). We have addressed this issue in a subgroup of NSTEMI patients enrolled in the SMILE trial.

Methods

Of the overall population of 1556 patients, 526 (33.8%) had an anterior wall NSTEMI, defined as an ST elevation <1 mm or an ST depression in at least two contiguous precordial leads with or without new abnormal Q waves. No patient of the SMILE Study received thrombolytic therapy or was reperfused. Patients were randomized, double-blind, to zofenopril (n = 253) or placebo (n = 273) for 6 weeks. The primary end point was the effect of treatment on the 6-week combined occurrence of death and severe congestive heart failure (CHF). Secondary end points included the evaluation of the 6-week rate of severe CHF as well as the 1-year mortality rate.

Results

After 6 weeks of treatment, zofenopril significantly reduced both the incidence of the primary end point (risk reduction 65%, 95% CI 20-80, 2P = .003) and the 6-week incidence of severe CHF (84%, 95% CI 33-97, 2P = .006) in NSTEMI patients. One-year mortality was also significantly reduced by zofenopril treatment (43%, 95% CI 14-57, 2P = .036).

Conclusions

Results of this post hoc analysis of the SMILE Study strongly suggest the benefit of the early administration of zofenopril even in patients with an anterior wall NSTEMI.

Section snippets

Subjects

The SMILE Study included 1556 patients admitted to 154 Italian coronary care units who were randomized to study treatment with an ACE inhibitor or placebo in addition to recommended pharmacological treatment. Details of the study protocol have been published elsewhere.7 Main SMILE Study inclusion criteria were the following: (1) male or female sex, (2) age 18 to 80 years, (3) admittance to the intensive care unit within 24 hours of the onset of chest pain typically associated with

Patients

A total of 526 (33.8%) of the 1556 patients included in the main SMILE Study had NSTEMI with chest pain. Mean treatment duration was 5.1 ± 0.4 weeks (median 5.4 weeks), whereas average follow-up time was 52 ± 2 weeks.

The number of NSTEMI patients was well balanced between the two treatment arms: 273 patients (51.9% of the NSTEMI patients) were assigned to placebo and 253 (48.1%) to zofenopril. As reported in Table I, the two treatment groups were homogeneous for baseline clinical

Discussion

The results of this post hoc analysis of the SMILE Study7 demonstrate that a 6-week treatment period with zofenopril is effective in reducing death and severe refractory CHF in non-thrombolysed NSTEMI patients9 and represent the first evidence of a prognostic benefit of early ACE inhibition in these patients. In addition to these clinically relevant observations, our study highlights the beneficial effect of short-term treatment with zofenopril on long-term survival after withdrawal of

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