Effect of proprotein convertase subtilisin kexin 9 inhibitors on platelet aggregation in patients with and without diabetes

BACKGROUND AND AIM: The impact of proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors on platelet reactivity in the setting of diabetes mellitus (DM) has not been adequately investigated. METHODS AND RESULTS: Out of 52 outpatients with atherosclerotic cardiovascular disease (ASCVD) with an indication for PCSK9 inhibitor alirocumab, 37 patients (mean age 68.1 ± 5.6 years, 62% males) were included in the study and retrospectively divided into two groups according to the presence of DM (DM+/DM-). A blood sample for platelet function testing was collected at baseline (T0), before initiation of alirocumab, and after 3 months of therapy (T90). Light transmission aggregometry was performed to study platelet aggregation, and results were expressed as percentage of maximum platelet aggregation (MPA). At 90-day follow-up, a significant reduction of total cholesterol and low-density lipoprotein cholesterol levels compared to baseline was observed in both DM+ and DM-groups. At baseline, MPA were comparable between the two groups. At T90, only in the DM + cohort, platelet aggregation induced by adenosine diphosphate (ADP) and arachidonic acid (AA) was significantly reduced compared to baseline (ADP 20 μM: 56.00 ± 28.67% vs 63.16 ± 33.69%, at T90 vs T0 respectively, p = 0.011; AA 1 mM: 28.68 ± 40.10% vs 41.74 ± 46.85%, p = 0.025). No significant change in platelet function from baseline was observed in patients DM- (p > 0.05 for all comparisons). CONCLUSION: The PCSK9 inhibitor alirocumab significantly reduced AA and ADP residual platelet aggregation after 90 days of therapy in patients with ASCVD and diabetes, but not in those without diabetes.