Aspirin does not interact with ACE inhibitors when both are given early after acute myocardial infarction: results of the GISSI-3 Trial.
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.
Latini
R
R
Department of Cardiovascular Research, Istituto di Ricerche Farmacologiche Mario Negri, Via Eritrea, 62 20157 Milan, Italy. latini@irfmn.mnegri.it
Santoro
E
E
Masson
S
S
Tavazzi
L
L
Maggioni
A P
AP
Franzosi
M G
MG
Barlera
S
S
Calvillo
L
L
Salio
M
M
Staszewsky
L
L
Labarta
V
V
Tognoni
G
G
D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D017706:Lisinopril / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D016017:Odds Ratio; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D012044:Regression Analysis; D015996:Survival Rate; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D010975:Platelet Aggregation Inhibitors; D003404:Creatinine; D017706:Lisinopril; D001241:Aspirin