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CLINICAL STUDIES

Clinical effects of early angiotensin-converting enzyme inhibitor treatment for acute myocardial infarction are similar in the presence and absence of aspirin

Systematic overview of individual data from 96,712 randomized patients

Roberto Latini, MD^*, Gianni Tognoni, MD^*, Aldo P. Maggioni, MD^* , Colin Baigent, MB, BCh, Eugene Braunwald, MD, Zheng-Ming Chen, PhD, Rory Collins, MB, BS, Marcus Flather, MD^||, MariaGrazia Franzosi, PhD^*, John Kjekshus, MD^¶, Lars Køber, MD^#, Li-Sheng Liu, MD^**, Richard Peto, FRS, Marc Pfeffer, MD, Fabrizio Pizzetti, MD, Eugenio Santoro, MSc^*, Peter Sleight, MD, Karl Swedberg, MD, Luigi Tavazzi, MD, Wen Wang, MSc^**, Salim Yusuf, MD^|||| on behalf of the Angiotensin-converting Enzyme Inhibitor Myocardial Infarction Collaborative Group¹

^* Istituto di Ricerche Farmacologiche "Mario Negri," Milano, Italy
Associazione Nazionale Medici-Cardiologi Ospedalieri, Firenze, Italy
Clinical Trial Service Unit, Radcliffe Infirmary, Oxford, United Kingdom
Brigham and Women’s Hospital, Boston, Massachusetts, USA
^|| Royal Brompton Hospital, London, United Kingdom
^¶ The National Hospital, University of Oslo, Oslo, Norway
^# Gentofte Hospital/University of Copenhagen, Hellerup, Denmark
^** Fu Wai Hospital, Beijing, China
Santo Spirito Hospital, Casale Monferrato (AL), Italy
Göteborg University, Göteborg, Sweden
Policlinico S. Matteo, Pavia, Italy
^|||| McMaster Clinic, Hamilton General Hospital, Hamilton, Ontario, Canada

Manuscript received November 16, 1998; revised manuscript received December 16, 1999, accepted February 9, 2000.

Reprint requests and correspondence: Dr. Roberto Latini, Department of Cardiovascular Research, Istituto Mario Negri, Via Eritrea, 62, 20157 Milano, Italy
latini{at}irfmn.mnegri.it

OBJECTIVES

We sought to determine whether the clinical effects of early angiotensin-converting enzyme (ACE) inhibitor (ACEi) treatment for acute myocardial infarction (MI) are influenced by the concomitant use of aspirin (ASA).

BACKGROUND

Aspirin and ACEi both reduce mortality when given early after MI. Aspirin inhibits the synthesis of vasodilating prostaglandins, and, in principle, this inhibition might antagonize some of the effects of ACEi. But it is uncertain whether, in practice, this influences the effects of ACEi on mortality and major morbidity after MI.

METHODS

This overview sought individual patient data from all trials involving more than 1,000 patients randomly allocated to receive ACEi or control starting in the acute phase of MI (0–36 h from onset) and continuing for four to six weeks. Data on concomitant ASA use were available for 96,712 of 98,496 patients in four eligible trials (and for none of 1,556 patients in the one other eligible trial).

RESULTS

Overall 30-day mortality was 7.1% among patients allocated to ACEi and 7.6% among those allocated to control, corresponding to a 7% (standard deviation [SD], 2%) proportional reduction (95% confidence interval 2% to 11%, p = 0.004). Angiotensin-converting enzyme inhibitor was associated with similar proportional reductions in 30-day mortality among the 86,484 patients who were taking ASA (6% [SD, 3%] reduction) and among the 10,228 patients who were not (10% [SD, 5%] reduction: chi-squared test of heterogeneity between these reductions = 0.4; p = 0.5). Angiotensin-converting enzyme inhibitor produced definite increases in the incidence of persistent hypotension (17.9% ACEi vs. 9.4% control) and of renal dysfunction (1.3% ACEi vs. 0.6% control), but there was no good evidence that these effects were different in the presence or absence of ASA (chi-squared for heterogeneity = 0.4 and 0.0, respectively; both not significant). Nor was there good evidence that the effects of ACEi on other clinical outcomes were changed by concomitant ASA use.

CONCLUSIONS

Both ASA and ACEi are beneficial in acute MI. The present results support the early use of ACEi in acute MI, irrespective of whether or not ASA is being given.

Abbreviations and Acronyms   ACE = angiotensin-converting enzyme   ACEi = angiotensin-converting enzyme inhibitor   ASA = aspirin   CCS = Chinese Cardiac Study   CONSENSUS = Cooperative New Scandinavian Enalapril Survival Study   GISSI = Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico   ISIS = International Study of Infarct Survival   MI = myocardial infarction   SD = standard deviation   SOLVD = Studies Of Left Ventricular Dysfunction

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