Monotherapy with the PCSK9 inhibitor alirocumab versus ezetimibe in patients with hypercholesterolemia: Results of a 24 week,double-blind,randomized Phase 3 trial

Background

Efficacy and safety of alirocumab were compared with ezetimibe in hypercholesterolemic patients at moderate cardiovascular risk not receiving statins or other lipid-lowering therapy.

Methods

In a Phase 3, randomized, double-blind, double-dummy study (NCT01644474), patients (low-density lipoprotein cholesterol [LDL-C] 100–190 mg/dL, 10-year risk of fatal cardiovascular events ≥ 1%–<5% [systemic coronary risk estimation]) were randomized to ezetimibe 10 mg/day (n = 51) or alirocumab 75 mg subcutaneously (via 1­mL autoinjector) every 2 weeks (Q2W) (n = 52), with dose up-titrated to 150 mg Q2W (also 1 mL) at week 12 if week 8 LDL-C was ≥ 70 mg/dL. Primary endpoint was mean LDL-C % change from baseline to 24 weeks, analyzed using all available data (intent-to-treat approach, ITT). Analyses using on-treatment LDL-C values were also conducted.

Results

Mean (SD) baseline LDL-C levels were 141.1 (27.1) mg/dL (alirocumab) and 138.3 (24.5) mg/dL (ezetimibe). The 24-week treatment period was completed by 85% of alirocumab and 86% of ezetimibe patients. Least squares mean (SE) LDL-C reductions were 47 (3)% with alirocumab versus 16 (3)% with ezetimibe (ITT; p < 0.0001) and 54 (2)% versus 17 (2)% (on-treatment; p < 0.0001). At week 12, before up-titration, alirocumab 75 mg Q2W reduced LDL-C by 53 (2)% (on-treatment). Injection site reactions were infrequent (< 2% and < 4% of alirocumab and ezetimibe patients, respectively).

Conclusions

Alirocumab demonstrated significantly greater LDL-C lowering versus ezetimibe after 24 weeks with the lower 75 mg Q2W dose sufficient to provide ≥ 50% LDL-C reduction in the majority of the patients. Adverse events were comparable between groups.     

Neck circumference for predicting the occurrence of future cardiovascular events: A 7.6-year longitudinal study

Background & aimsThis study aimed to investigate whether neck circumference (NC) could be used to predict future cardiovascular (CV) events in a community-based Chinese cohort.Methods and resultsWe enrolled 1435 participants aged 50–80 years (men, 43.62%) from communities in Shanghai. High NC was defined as NC ≥ 38.5 cm in men and NC ≥ 34.5 cm in women. Kaplan-Meier analysis and Cox proportional hazards regression were performed to explore the association between NC and CV events. During a mean follow-up period of 7.6 years, 148 CV events (10.31%) occurred. The incidence of CV events was higher in men than in women (83 (13.26%) vs. 65 (8.03%), P = 0.002). Multivariable-adjusted Cox regression analysis showed that for every 1-SD increase in NC in the whole population, the hazard ratio (HR) of CV events was 1.45 (95% confidence interval [CI], 1.15–1.83). The dose-response association between NC and CV events was significant in men (HR, 1.37, 95% CI, 1.10–1.71) but not in women (HR, 1.19, 95% CI, 0.94–1.52). In comparison with participants showing low baseline NC, those with high baseline NC showed a significantly higher risk of CV events (HR, 1.59, 95% CI, 1.14–2.22). Further stratified by sex, the positive association remained significant in men (HR, 1.90, 95% CI, 1.21–2.98) but not in women (HR, 1.25, 95% CI, 0.75–2.07).ConclusionNC was significantly associated with the risk of future CV events in middle-aged and elderly populations in the community and was a better predictor in men.