Association of PCSK9 inhibitors with mortality: insights from a retrospective cohort analysis

Abstract

Abstract Aims Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are effective in reducing cardiovascular events, but their impact on all-cause mortality and medical utilization compared to statins is unclear. This study investigated PCSK9 inhibitor use and its impact on mortality and medical utilization vs. statins, using TriNetX database data with up to 9 years of follow-up. Methods and results This retrospective cohort study analysed TriNetX data spanning 1 July 2015, to 31 December 2023, including 79 194 PCSK9 inhibitor users (alirocumab, evolocumab, inclisiran) and 5 437 513 statin users with hyperlipidaemia. The primary outcomes were all-cause mortality and medical utilization, including hospital inpatient services, emergency department visits, critical care, and mechanical ventilation. Propensity score matching showed that PCSK9 inhibitor use was associated with a 28.3% lower risk of all-cause mortality [adjusted hazard ratio (aHR) 0.717, 95% confidence interval (CI): 0.673–0.763] and significant reductions in medical utilization (hospital inpatient services usage: aHR 0.692, 95% CI: 0.664–0.721; emergency department services: aHR 0.756, 95% CI: 0.726–0.788; critical care services: aHR 0.619, 95% CI: 0.578–0.664; and mechanical ventilation: aHR 0.537, 95% CI: 0.484–0.596) compared to statins. These findings were consistent across various demographics and clinical subgroups. The sensitivity analyses supported the robustness of the findings. Conclusion PCSK9 inhibitors significantly reduced all-cause mortality and medical utilization compared to statins, suggesting their important role in dyslipidaemia management, particularly for statin-naïve or intolerant patients. Further research, including randomized controlled trials, is needed to confirm these findings and explore the underlying mechanisms.