Evaluation of the effects of aspirin combined with angiotensin-converting enzyme inhibitors in patients with coronary artery disease

BACKGROUND: Several studies have suggested that there may be an interaction between angiotensin-converting enzyme (ACE) inhibitors and aspirin in pati ents with congestive heart failure, such that their benefits are attenuated when used in combination. Whether this interaction exists in patients with coronary artery disease is not known. SUBJECTS AND METHODS: Patients enrolled in two large trials, Global Utiliza tion of Streptokinase and Tissue Plasminogen Activator for Occluded Coronar y Arteries (GUSTO-I) and Evaluation in PTCA to Improve Long-Term Outcome wi th Abciximab GP IIb/IIIa Blockade (EPILOG), were stratified according to us e of aspirin and ACE inhibitors on discharge from the hospital. In the EPIL OG trial, left ventricular systolic function was assessed by contrast ventr iculography. The primary endpoint was all-cause mortality at 1 year. EPILOG patients, ail of whom were receiving aspirin, were also examined for the c ombined endpoint of death or nonfatal myocardial infarction. Stratified and multivariate analyses were used to adjust for baseline differences in pati ent characteristics. RESULTS: We studied 31,622 patients in the GUSTO-I trial and 2,619 patients in the EPILOG trial. There were 615 deaths among the GUSTO-I patients and 45 deaths among the EPILOG patients at 1 year. Unadjusted mortality was gre ater among patients treated with both ACE inhibitors and aspirin than among patients treated with aspirin alone (3.3% versus 1.6%, P < 0.001 for GUSTO -I; and 3.7% versus 1.2%, P < 0.001 for EPILOG). Similarly, the composite e ndpoint of death or nonfatal myocardial infarction was more frequent among EPILOG patients who were taking ACE inhibitors (6.3% versus 3.3%, P = 0.001 ). After adjusting for confounders, combined use of aspirin and ACE inhibit ors was associated with increased mortality in GUSTO-I patients (hazard rat io [HR] = 2.2, 95% confidence interval [CI]: 1.1 to 4.3, P = 0.03) com pare d with aspirin alone. In EPILOG patients, after adjusting for clinical fact ors and extent of left ventricular dysfunction, the combination of aspirin and ACE inhibitors was associated with an increased risk of death (HR = 2.1 , 95% CI: 1.1 to 3.8, P = 0.02) and of death or nonfatal myocardial infarct ion (HR = 1.5, 95% CI: 1.1 to 2.5, P = 0.02) compared with aspirin alone. CONCLUSION: These observational findings suggest the possibility of an inte raction between aspirin and ACE inhibitors among patients with ischemic hea rt disease. Further study of this issue is warranted. (C) 2000 by Excerpta Medica, Inc.