Baseline Statin Exposure and Incident Acute Myocardial Infarction in Adults Aged >=75 Years Without Prior Cardiovascular Disease: A Population-Based Cohort Study

Background: Adults aged [≥]75 years represent a rapidly growing population at risk of acute myocardial infarction (AMI), yet they remain markedly underrepresented in statin trials for primary prevention. The limited evidence base, together with multimorbidity, functional heterogeneity, and competing mortality risks, has contributed to uncertainty regarding the potential role of statins in very old adults. This study evaluated the association between baseline statin exposure and incident AMI among community-dwelling adults aged [≥]75 years without prior cardiovascular disease. Methods: We conducted a retrospective population-based cohort study using linked primary-care, hospital, laboratory, and pharmacy dispensing data from the Community of Madrid. Statin exposure was ascertained during a 24-month exposure-assessment period from 1 January 2018 to 31 December 2019 and classified at a landmark date of 1 January 2020, when outcome follow-up began. Participants were classified as exposed if they had received at least two statin dispensations during the exposure-assessment period and had no record of prior lipid-lowering therapy before 2018. Individuals with prior cardiovascular disease, type 1 diabetes, cancer, dementia, or advanced chronic kidney disease were excluded. Missing data were addressed using multiple imputation. The association between baseline statin exposure and incident AMI was estimated using multivariable Cox proportional hazards regression. Propensity-score matching and Fine-Gray competing-risk regression, with all-cause mortality as the competing event, were performed as sensitivity analyses. Results: Among 174,014 individuals included in the final cohort, 32,698 (18.8%) met the criteria for baseline statin exposure. The mean age was 82.5 years. During a median follow-up of 5 years, AMI occurred in 533 (1.63%) statin-exposed individuals and 2722 (1.93%) non-exposed individuals (p=0.0003). The observed absolute risk difference was 0.30 percentage points (95% CI, 0.14-0.45), corresponding to an estimated observational number needed to treat of 338 over 5 years (95% CI, 222-708). In the fully adjusted Cox model, baseline statin exposure was associated with a lower risk of incident AMI (HR, 0.805; 95% CI, 0.731-0.887). In the full-cohort Fine-Gray model accounting for competing mortality, baseline statin exposure remained associated with a lower cumulative incidence of AMI (sHR, 0.823; 95% CI, 0.748-0.905). After propensity-score matching, the association remained in the competing-risk analysis (subdistribution HR, 0.852; 95% CI, 0.738-0.983). Conclusions: In this large population-based cohort of adults aged [≥]75 years without prior cardiovascular disease, baseline statin exposure was associated with a lower incidence of AMI across several analytical approaches. The observed absolute risk difference was modest, and the findings should be interpreted in light of the observational design, residual confounding, and the potential for selection related to survival to the landmark date. Further randomized evidence is needed to determine whether this association reflects a causal effect of statin therapy in very old adults. Keywords: Statins; primary prevention; acute myocardial infarction; aged [≥]75 years; landmark analysis; competing risks; propensity-score matching; real-world data.