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 patients 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.


METHODS
Patients enrolled in two large trials, Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-I) and Evaluation in PTCA to Improve Long-Term Outcome with Abciximab GP IIb/IIIa Blockade (EPILOG), were stratified according to use of aspirin and ACE inhibitors on discharge from the hospital. In the EPILOG trial, left ventricular systolic function was assessed by contrast ventriculography. The primary endpoint was all-cause mortality at 1 year. EPILOG patients, all of whom were receiving aspirin, were also examined for the combined endpoint of death or nonfatal myocardial infarction. Stratified and multivariate analyses were used to adjust for baseline differences in patient 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 greater 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 endpoint 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 inhibitors was associated with increased mortality in GUSTO-I patients (hazard ratio [HR] = 2.2, 95% confidence interval [CI]: 1.1 to 4.3, P = 0.03) compared with aspirin alone. In EPILOG patients, after adjusting for clinical factors 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 infarction (HR = 1.5, 95% CI: 1.1 to 2.5, P = 0.02) compared with aspirin alone.


CONCLUSIONS
These observational findings suggest the possibility of an interaction between aspirin and ACE inhibitors among patients with ischemic heart disease. Further study of this issue is warranted.
Peterson
J G
JG
Department of Cardiology, Cleveland Clinic Foundation, Cleveland, Ohio, USA.
Topol
E J
EJ
Sapp
S K
SK
Young
J B
JB
Lincoff
A M
AM
Lauer
M S
MS
D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D001241:Aspirin / Q000037:antagonists & inhibitors* / Q000627:therapeutic use; D003327:Coronary Disease / Q000150:complications / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D016757:Death, Sudden, Cardiac / Q000209:etiology; D004359:Drug Therapy, Combination; D005260:Female; D005343:Fibrinolytic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000209:etiology; D010351:Patient Discharge; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D016019:Survival Analysis; D013599:Systole / Q000187:drug effects; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000209:etiology; D016277:Ventricular Function, Left / Q000187:drug effects*
D000806:Angiotensin-Converting Enzyme Inhibitors; D016861:Cyclooxygenase Inhibitors; D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; D001241:Aspirin