Aspirin (ASA) and
angiotensin-converting enzyme inhibitor (ACEi)
therapy reduce mortality when administered early after the onset of
myocardial infarction. ASA can antagonize some effects of ACEi
therapy by inhibiting the synthesis of vasodilating
prostaglandins; however, the evidence for this effect from large controlled trials is contradictory. The authors analyzed a database of 18,895 patients of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardio-3 (GISSI-3) Trial in which patients were allocated either to receive
lisinopril or not to receive
lisinopril within 24 hours of the onset of symptoms of
myocardial infarction. The aim of the study was to verify the possible negative interaction between ASA and the ACEi
lisinopril in the postacute phase of acute
myocardial infarction. Of 18,895 analyzable patients, 15,841 received ASA at entry. Overall
lisinopril reduced 42-day mortality from 7.1% to 6.3%. In patients receiving ASA, mortality was reduced by
lisinopril from 6.0% to 5.4%, and from 13.0% to 10.8% in patients not receiving ASA. The difference in proportional reductions of mortality corresponds to the fact that a more marked
lisinopril effect is seen in patients at higher baseline risk across all study subgroups, one of which coincides with the
no-ASA group. The analysis of the inhospital incidence of major clinical events did not reveal a potentially negative interaction between ASA and
lisinopril. The same findings were obtained from the analysis of reinfarction at 42 days. The interaction between ASA and
lisinopril was also tested by multivariate analysis adjusted for confounding variables at entry, and the interaction tests were not statistically significant. Serum
creatinine levels at 42 days were significantly higher in
lisinopril group than in the control group. Systolic and diastolic blood pressures in
lisinopril group were significantly lower than controls at 42 days. The effect of
lisinopril on
creatinine and blood pressure did not differ between the ASA and
no-ASA groups. ASA does not decrease the mortality benefit of early
lisinopril after
myocardial infarction, nor does it increase the risk of major adverse events.
Lisinopril is safe and effective when given early after the onset of
myocardial infarction, regardless of a concomitant administration of ASA started early and continued over a 6-week period.