The Effect of PCSK9 Monoclonal Antibodies on Platelet Reactivity and Cardiovascular Events in Patients Receiving Primary Percutaneous Coronary Intervention: A Propensity Score-Matched Analysis.

Abstract

Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies (mAbs) have demonstrated promising effects in lowering cardiovascular incidents among patients with acute coronary syndrome. However, their influence on early platelet reactivity after primary percutaneous coronary intervention (PPCI) remains unclear.

Objectives: This research sought to investigate the effects of entirely human anti-PCSK9 antibodies on platelet function as measured by thrombelastography and 12-month postoperative results in patients receiving PPCI and treated with ticagrelor-based dual antiplatelet therapy.

Methods: This single-center prospective study was conducted at Zhongshan Hospital, Fudan University, China, between January 2021 and June 2023. Patients were divided into two groups: those receiving standard statin therapy (statin-only group) and those receiving additional PCSK9 mAbs (either evolocumab 140 mg or alirocumab 75 mg, subcutaneously, every 2 weeks; PCSK9 mAb group). A total of 1250 eligible patients were enrolled. To equalize baseline characteristics, propensity score matching was conducted in a 1:1 ratio, resulting in 310 patients per group. Platelet activity was measured using thrombelastography 5 days after PPCI, presented as adenosine diphosphate-induced maximal amplitude (MA_ADP). The primary clinical outcome was the occurrence of major adverse cardiovascular events, which included cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, and coronary revascularization, measured over a 12-month period.

Results: At 5 days after PPCI, the PCSK9 mAb group exhibited levels of MA_ADP that were significantly lower than those in the statin-only group (17.10 ± 9.52 mm vs. 20.73 ± 12.07 mm, P < 0.001). The use of PCSK9 mAbs was significantly correlated with reduced MA_ADP (β - 0.166, P < 0.001). The occurrence of major adverse cardiovascular events in the PCSK9 mAb group was significantly lower than in the statin-only group. Furthermore, individuals in the top MA_ADP tertile (MA_ADP > 21.7 mm) plus statin-only subgroup exhibited the lowest rate of cumulative event-free survival.

Conclusion: Incorporating PCSK9 mAbs into ticagrelor-based dual antiplatelet therapy significantly reduced platelet reactivity and correlated with better cardiovascular results over a 12-month period. These findings support the use of PCSK9 mAbs as an effective adjunctive therapy in the management of acute coronary syndrome.