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CLINICAL STUDY: MYOCARDIAL INFARCTION

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

Pieter J. de Kam, MSc^*, Adriaan A. Voors, MD, PhD , Maarten P. van den Berg, MD, PhD^*, Dirk J. van Veldhuisen, MD, PhD, FACC^*, Jan Brouwer, MD, PhD^*, Harry J. G. M. Crijns, MD, PhD^*, Claudio Borghi, MD, Ettore Ambrosioni, MD, Judith S. Hochman, MD^||, Thierry H. LeJemtel, MD^¶, Jan-Herre Kingma, MD, PhD, Martin St. John Sutton, MD, MBBS, FACC^#, Wiek H. van Gilst, PhD^* on behalf of the FAMIS CAPTIN and CATS Investigators

^* Department of Cardiology, University Hospital, Groningen, The Netherlands
Department of Cardiology, St. Anthonius Hospital, Nieuwegein, The Netherlands
Department of Clinical Pharmacology, University of Groningen, Groningen, The Netherlands
Department of Cardiology, University of Bologna, Bologna, Italy
^|| Department of Cardiology, St. Luke’s–Roosevelt Hospital, New York, New York, USA
^¶ Division of Cardiology, Albert Einstein College of Medicine, New York, New York, USA
^# Cardiovascular Division, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania, USA

Manuscript received February 14, 2000; revised manuscript received July 7, 2000, accepted August 24, 2000.

Reprint requests and correspondence: Dr. D. J. van Veldhuisen, Department of Cardiology/Thoraxcenter, University Hospital Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands
d.j.van.veldhuisen{at}thorax.azg.nl

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.

Abbreviations and Acronyms   ACE = angiotensin-converting enzyme   CAPTIN = CAPtopril plus Tissue plasminogen activator following acute myocardial INfarction study   CATS = Captopril And Thrombolysis Study   CONSENSUS-II = COoperative New Scandinavian ENalapril SUrvival Study II   FAMIS = Fosinopril in Acute Myocardial Infarction Study   GISSI-3 = Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto miocardico-3   HOPE = Heart Outcomes Prevention Evaluation study   LV = left ventricular   MI = myocardial infarction   SAVE = Survival And Ventricular Enlargement trial

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