Effect of evidence‐based drug therapy on long‐term outcomes in patients discharged after myocardial infarction: a nested case–control study in Italy

PURPOSE: There are some methodological concerns regarding results from observational studies about the effectiveness of evidence-based (EB) drug therapy in secondary prevention after myocardial infarction. The present study used a nested case–control approach to address these major methodological limitations. METHODS: A cohort of 6880 patients discharged from hospital after acute myocardial infarction (AMI) in 2006–2007 was enrolled and followed-up throughout 2009. Exposure was defined as adherence to each drug in terms of the proportion of days covered (cutoff ≥ 75%). Composite treatment groups, that is, groups with no EB therapy or therapy with one, two, three, or four EB drugs), were analyzed. Outcomes were overall mortality and reinfarction. Nested case–control studies were performed for both outcomes, matching four controls to every case (841 deaths, 778 reinfarctions) by gender, age, and individual follow-up. The association between exposure to EB drug therapy and outcomes was analyzed using conditional logistic regression, adjusting for revascularization procedures, comorbidities, duration of index admission, and use of the study drugs prior to admission. RESULTS: Mortality and reinfarction risk decreased with the use of an increasing number of EB drugs. Combinations of two or more EB drugs were associated with a significant protective effect (p < 0.001) versus no EB drugs (mortality: 4 EB drugs: ORadj = 0.35; 95%CI: 0.21–0.59; reinfarction: 4 EB drugs: ORadj = 0.23; 95%CI: 0.15–0.37). CONCLUSIONS: These findings of the beneficial effects of EB polytherapy on mortality and morbidity in a population-based setting using a nested case–control approach strengthen existing evidence from observational studies.