Early PCSK9 inhibitor subscription during episode of acute myocardial infarction (EPISODE-AMI) study

Abstract Background/Introduction Evidence supports proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor therapy on top of statin could improve cardiovascular outcomes in patients post acute coronary syndrome (1-12 months after index event). However, there is no large-scale real-world study to evaluate the effect of early subscription of a PCSK9 inhibitor during acute phase of acute myocardial infarction (AMI) on long-term major adverse cardiovascular event (MACE), all-cause mortality and medical utilization. Purpose To evaluate the effect of early subscription of a PCSK9 inhibitor, either alirocumab, evolocumab, or inclisiran, during acute phase of AMI on long-term cardiovascular outcomes and medical resources utilization. Methods This retrospective cohort study was performed by analyzing aggregated data from the US collaborative network of TriNetX, a global federated healthcare research network providing access to real-time electronic medical records among large healthcare organizations. Data was extracted between January 1, 2016, and June 30, 2024. The study population was divided into two cohorts, group 1 (PCSK9 inhibitor) and group 2 (statin), who should use each drug within 5 days of index event. Evaluated endpoints included MACE, all-cause mortality, and medical utilization at one year of follow up. Results A total of 575,572 eligible AMI patients (2,245 in group 1 and 573,327 in group 2) were identified. After propensity score matching (n = 1,594 in each group), as compared to statin users, the risk of MACE (hazard ratio (HR): 0.828, 95% confidence interval (CI): 0.724-0.947) and all-cause mortality (HR: 0.684, 95% CI: 0.474-0.986) in the PCSK9 inhibitor users was significantly reduced. PCSK9 inhibitor treatment was associated with less hospital inpatient services usage (HR: 0.744, 95% CI: 0.656-0.844), emergency department services (HR 0.713, 95% CI: 0.602-0.844), and mechanical ventilation (HR 0.634, 95% CI: 0.447-0.900). Subgroup and sensitivity analyses showed consistent results regarding MACE and all-cause mortality in favor of PCSK9 inhibitor treatment. Conclusions Early subscription of a PCSK9 inhibitor during acute phase of AMI was associated with a lower risk of MACE, all-cause mortality, and medical utilization.