Réduction des événements artériels périphériques et des ETEV induite par l'alirocumab chez les patients avec SCA et lien avec la baisse de la Lp(a).

Background: Patients with acute coronary syndrome (ACS) are at risk for peripheral artery disease (PAD) events and venous thromboembolism (VTE). Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors reduce lipoprotein(a) and low-density lipoprotein cholesterol (LDL-C) levels. Our objective was to ascertain whether PCSK9 inhibition reduces the risk of PAD events or VTE after ACS, and if such effects are related to levels of lipoprotein(a) or LDL-C.

Methods: This was a prespecified analysis of the ODYSSEY OUTCOMES randomized clinical trial, which was conducted in 18 924 patients with recent ACS on intensive or maximumtolerated statin treatment who were randomized to the PCSK9 inhibitor alirocumab or placebo. In a prespecified analysis, PAD events (critical limb ischemia, limb revascularization, or amputation for ischemia) and VTE (deep vein thrombosis or pulmonary embolism) were assessed. LDL-C was corrected for cholesterol content in lipoprotein(a).

Results: At baseline, median lipoprotein(a) and LDL-Ccorrected were 21 and 75 mg/dL, respectively; with alirocumab, median relative reductions were 23.5% and 70.6%, respectively. PAD events and VTE occurred in 246 and 92 patients, respectively. In the placebo group, risk of PAD events was related to baseline quartile of lipoprotein(a) (Ptrend=0.0021), but not baseline quartile of LDL-Ccorrected (Ptrend=0.06); VTE tended to associate with baseline quartile of lipoprotein(a) (Ptrend=0.06), but not LDL-Ccorrected (Ptrend=0.85). Alirocumab reduced risk of PAD events (hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.54–0.89; P=0.004), with nonsignificantly fewer VTE events (HR, 0.67; 95% CI, 0.44–1.01; P=0.06). Reduction in PAD events with alirocumab was associated with baseline quartile of lipoprotein(a) (Ptrend=0.03), but not LDL-Ccorrected (Ptrend=0.50). With alirocumab, the change from baseline to Month 4 in lipoprotein(a), but not LDL-Ccorrected, was associated with the risk of VTE and the composite of VTE and PAD events.

Conclusions: In statin-treated patients with recent ACS, risk of PAD events is related to lipoprotein(a) level and is reduced by alirocumab, particularly among those with high lipoprotein(a). Further study is required to confirm whether risk of VTE is related to lipoprotein(a) level and its reduction with alirocumab.