Mortality reduction with implanted defibrillator for primary prevention of sudden death after Myocardial Infarction: temporal trends in the PROFID study

Background and aim: Randomized trials conducted in the early 2000s established the survival benefit of primary prevention implantable cardioverter-defibrillator (ICD) therapy in patients with reduced left ventricular ejection fraction (LVEF) after myocardial infarction. However, management of myocardial infarction and heart failure has substantially evolved since that time. We investigated whether the estimated association between primary prevention ICD implantation in post-myocardial infarction patients with reduced LVEF and mortality reduction has changed over time. Methods: We analyzed individual participant data from 32,214 patients with LVEF ≤35% after myocardial infarction included in the PROFID pooled cohort, comprising 7,477 patients carrying a primary prevention ICD (ICD patients) and 24,737 patients without an ICD (non-ICD patients). The primary endpoint was all-cause mortality. Propensity scores were estimated using multivariable logistic regression including age, sex, LVEF, renal function, and diabetes, and overlap weighting was applied to balance treatment groups. Time period-specific analyses were performed across three prespecified time periods defined by inclusion year: 1995-2004, 2005-2014, and 2015-2020. Weighted cumulative mortality curves were generated for each time period. Temporal changes in the estimated association between ICD implantation and mortality reduction were assessed using a weighted Cox proportional hazards model. Results: A total of 12,097 deaths occurred during a mean follow-up of 43.7 months. The estimated association between ICD implantation and mortality changed significantly across time (P for interaction <0.001). In weighted time period-specific analyses, the estimated mortality reduction associated with ICD implantation progressively decreased over more recent periods. The hazard ratio for ICD versus non-ICD patients was 0.54 (95% CI 0.47-0.62; P<0.001) in 1995-2004, 0.67 (95% CI 0.62-0.72; P<0.001) in 2005-2014, and 0.89 (95% CI 0.73-1.07; P=0.221) in 2015-2020, with negligible separation of the weighted cumulative mortality curves in the most recent time period. Conclusions: In this analysis including a large cohort of post-myocardial infarction patients with reduced LVEF, the estimated mortality reduction associated with primary prevention ICD implantation progressively decreased over time.