Interaction Between Enalapril and Aspirin on Mortality After Acute Myocardial Infarction: Subgroup Analysis of the Cooperative New Scandinavian Enalapril Survival Study II (CONSENSUS II)

The use of angiotensin-converting enzyme (ACE) inhibitors early after an acute myocardial infarction to reduce mortality has been studied in several trials with inconsistent results. Aspirin (ASA) has become a well-documented therapeutic adjunct in patients with coronary heart disease. Attention has...

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Bibliographic Details
Published in:The American journal of cardiology 1997-01, Vol.79 (2), p.115-119
Main Authors: Nguyen, Khang Ngoc, Aursnes, Ivar, Kjekshus, John
Format: Article
Language:English
Subjects:
Aged
Angiotensin-Converting Enzyme Inhibitors - administration & dosage
Angiotensin-Converting Enzyme Inhibitors - therapeutic use
Anti-Inflammatory Agents, Non-Steroidal - administration & dosage
Anti-Inflammatory Agents, Non-Steroidal - antagonists & inhibitors
Anti-Inflammatory Agents, Non-Steroidal - therapeutic use
Aspirin
Aspirin - administration & dosage
Aspirin - antagonists & inhibitors
Aspirin - therapeutic use
Biological and medical sciences
Cardiovascular system
Cause of Death
Confidence Intervals
Double-Blind Method
Drug Interactions
Drug therapy
Enalapril - administration & dosage
Enalapril - antagonists & inhibitors
Enalapril - therapeutic use
Female
Follow-Up Studies
Forecasting
Heart attacks
Heart Failure - physiopathology
Humans
Logistic Models
Male
Medical research
Medical sciences
Mortality
Myocardial Infarction - drug therapy
Pharmacology. Drug treatments
Placebos
Recurrence
Retrospective Studies
Scandinavian and Nordic Countries
Survival Rate
Treatment Outcome
Vasodilator agents. Cerebral vasodilators
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Summary:The use of angiotensin-converting enzyme (ACE) inhibitors early after an acute myocardial infarction to reduce mortality has been studied in several trials with inconsistent results. Aspirin (ASA) has become a well-documented therapeutic adjunct in patients with coronary heart disease. Attention has recently been focused on a possible interaction between ASA and ACE inhibitors. We therefore reanalyzed data from the Cooperative New Scandinavian Enalapril Survival Study II (CONSENSUS II) to find any evidence of differential effects of the ACE inhibitor enalapril in subgroups defined by use of ASA at baseline. Logistic regression tested the multiplicative interaction. We used Rothman synergy index S, which would be equal to unity under additivity, and less than unity when suggesting antagonism, to examine the postulated interaction with departure from an additive model. Logistic regression showed that the enalapril-ASA interaction term was a significant predictor of mortality at the end of the study (p = 0.047), and was a borderline significant predictor of mortality 30 days after randomization (p = 0.085). The Rothman synergy index S was 0.66 (95% confidence interval 0.46 to 0.94) for mortality at the end of the study, and 0.68 ( 0.44 to 1.04) for 30-day mortality, indicating antagonism between enalapril and ASA with departure from an additive model. Thus, we found evidence of enalapril-ASA interaction. The effect of enalapril was less favorable among patients taking ASA than among patients not taking ASA at baseline.
ISSN:0002-9149
1879-1913
DOI:10.1016/S0002-9149(96)00696-0