Patients with atherosclerotic cardiovascular disease (ASCVD) remain at high residual risk even before a first myocardial infarction or ischemic stroke. Real-world data published in the European Heart Journal evaluated whether proprotein convertase subtilisin/kexin type 9 inhibitor monoclonal antibodies (PCSK9i mAb) were associated with lower long-term ischemic events and mortality in this setting.

This retrospective cohort study used the Optum Research Database to identify patients initiating PCSK9i mAb between January 2016 and December 2022. A 1:2 propensity score-matched comparator cohort of non-initiators was created. The analysis included 19,670 patients, comprising 6,545 initiators and 13,125 non-initiators.

The primary composite endpoint included non-fatal myocardial infarction (MI), non-fatal ischemic stroke, or all-cause mortality. In intention-to-treat analysis using a parametric G-formula, estimated 5-year event rates were 17.5% (95% CI 15.5% to 19.5%) with PCSK9i mAb and 25.4% (95% CI 23.6% to 27.1%) without therapy, corresponding to relative and absolute risk reductions of 30.9% and 7.8%, respectively.

Individual endpoints also favored treatment, with relative risk reductions of 28.3% for MI (P < 0.0001), 26.4% for ischemic stroke (P = 0.02), and 28.5% for all-cause mortality (P < 0.0001). Among initiators, mean low-density lipoprotein cholesterol (LDL-C) declined from 117.8 mg/dL at baseline to 54.7 mg/dL during treatment, an absolute reduction of 63.1 mg/dL.

These findings suggest PCSK9i mAb therapy was associated with lower ischemic event and mortality rates in routine care among ASCVD patients without prior events.