[Efficacy and safety of alirocumab versus ezetimibe in high cardiovascular risk Chinese patients with hyperlipidemia: ODYSSEY EAST Study-Chinese sub-population analysis].

Objective: To compare the efficacy and safety profile of alirocumab (PCSK9 inhibitor) versus ezetimibe on top of maximally tolerated statin dose in high cardiovascular risk Chinese patients with hyperlipidemia. Methods: The ODYSSEY EAST study was a randomized, double-blinded, double dummy, active-control, parallel group, multi-centers clinical trial, the Chinese sub-population included 456 patients with hyperlipidemia and high cardiovascular risk on maximally tolerated statin dose. Patients were randomized (2∶1) to receive the subcutaneous injection of alirocumab (75 mg Q2W; with dose up titration to 150 mg Q2W at week 12 if low-density lipoprotein cholesterol (LDL-C) was ≥1.81 mmol/L at week 8) or the oral administration of ezetimibe (10 mg daily) for 24 weeks. The primary endpoint was percentage change in calculated LDL-C from baseline to week 24. Key secondary efficacy endpoints included percentage change from baseline to week 12 or 24 in LDL-C (week 12) and other lipid parameters, including apolipoprotein (Apo) B, non-high-density lipoprotein cholesterol (non-HDL-C), TC, lipoprotein(a) (Lp(a)), HDL-C, fasting triglycerides (TG), and Apo A1, and the proportion of patients reaching LDL-C<1.81 mmol/L at week 24. Safety profile of therapeutic drugs was also assessed during the treatment period. Results: The mean age of 456 Chinese patients was (59.5±10.9) years, 341(74.8%) patients were male, 303 patients (66.4%) in alirocumab group and 153 patients (33.5%) in ezetimibe group. Demographic characteristics, disease characteristics, and lipid parameters at baseline were similar between the two groups. LDL-C was reduced more from baseline to week 12 and 24 in alirocumab group versus ezetimibe group, the difference of their least-squares mean (standard error) percent change were(-35.2±2.2)% and (-36.9±2.5)% (both P<0.001). At 12 weeks, alirocumab had significant reduction on Lp(a), Apo B, total cholesterol and non HDL-C, the difference of their least-squares mean (standard error) percent change were (-40.3±2.8)%, (-27.7±1.8)%, (-19.6±1.5)% and (-27.7±1.9)%, respectively (all P<0.001). At 24 weeks, the percent of patients who reached LDL-C<1.81 mmol/L and LDL-C<1.42 mmol/L was significantly higher in alirocumab group (85.3% and 70.5%) than in ezetimibe group (42.2% and 17.0%, both P<0.001), and alirocumab use was also associated with significant reduction on Lp(a), Apo B, total cholesterol and non HDL-C, the difference of their least-squares mean (standard error) percent change were (-37.2±2.8)%, (-29.1±2.0)%, (-21.6±1.6)% and (-29.6±2.2)%, respectively (all P<0.001). The incidence of treatment related adverse events was similar between the two treatment groups (223/302 patients (73.8%) in alirocumab group and 109/153 patients (71.2%) in ezetimibe group). Respiratory infection, urinary infection, dizziness and local injection-site reactions were the most frequently reported adverse events. Conclusions: In high cardiovascular risk patients with hyperlipidemia from China on maximally tolerated statin dose, the reduction of LDL-C induced by alirocumab is more significant than that induced by ezetimibe. Both treatments were generally safe during the observation period of study.

Efficacy and safety of alirocumab versus ezetimibe in high cardiovascular risk Chinese patients with hyperlipidemia: ODYSSEY EAST Study-Chinese sub-population analysis / 中华心血管病杂志

Objective: To compare the efficacy and safety profile of alirocumab (PCSK9 inhibitor) versus ezetimibe on top of maximally tolerated statin dose in high cardiovascular risk Chinese patients with hyperlipidemia. Methods: The ODYSSEY EAST study was a randomized, double-blinded, double dummy, active-control, parallel group, multi-centers clinical trial, the Chinese sub-population included 456 patients with hyperlipidemia and high cardiovascular risk on maximally tolerated statin dose. Patients were randomized (2∶1) to receive the subcutaneous injection of alirocumab (75 mg Q2W; with dose up titration to 150 mg Q2W at week 12 if low-density lipoprotein cholesterol (LDL-C) was ≥1.81 mmol/L at week 8) or the oral administration of ezetimibe (10 mg daily) for 24 weeks. The primary endpoint was percentage change in calculated LDL-C from baseline to week 24. Key secondary efficacy endpoints included percentage change from baseline to week 12 or 24 in LDL-C (week 12) and other lipid parameters, including apolipoprotein (Apo) B, non-high-density lipoprotein cholesterol (non-HDL-C), TC, lipoprotein(a) (Lp(a)), HDL-C, fasting triglycerides (TG), and Apo A1, and the proportion of patients reaching LDL-C<1.81 mmol/L at week 24. Safety profile of therapeutic drugs was also assessed during the treatment period. Results: The mean age of 456 Chinese patients was (59.5±10.9) years, 341(74.8%) patients were male, 303 patients (66.4%) in alirocumab group and 153 patients (33.5%) in ezetimibe group. Demographic characteristics, disease characteristics, and lipid parameters at baseline were similar between the two groups. LDL-C was reduced more from baseline to week 12 and 24 in alirocumab group versus ezetimibe group, the difference of their least-squares mean (standard error) percent change were(-35.2±2.2)% and (-36.9±2.5)% (both P<0.001). At 12 weeks, alirocumab had significant reduction on Lp(a), Apo B, total cholesterol and non HDL-C, the difference of their least-squares mean (standard error) percent change were (-40.3±2.8)%, (-27.7±1.8)%, (-19.6±1.5)% and (-27.7±1.9)%, respectively (all P<0.001). At 24 weeks, the percent of patients who reached LDL-C<1.81 mmol/L and LDL-C<1.42 mmol/L was significantly higher in alirocumab group (85.3% and 70.5%) than in ezetimibe group (42.2% and 17.0%, both P<0.001), and alirocumab use was also associated with significant reduction on Lp(a), Apo B, total cholesterol and non HDL-C, the difference of their least-squares mean (standard error) percent change were (-37.2±2.8)%, (-29.1±2.0)%, (-21.6±1.6)% and (-29.6±2.2)%, respectively (all P<0.001). The incidence of treatment related adverse events was similar between the two treatment groups (223/302 patients (73.8%) in alirocumab group and 109/153 patients (71.2%) in ezetimibe group). Respiratory infection, urinary infection, dizziness and local injection-site reactions were the most frequently reported adverse events. Conclusions: In high cardiovascular risk patients with hyperlipidemia from China on maximally tolerated statin dose, the reduction of LDL-C induced by alirocumab is more significant than that induced by ezetimibe. Both treatments were generally safe during the observation period of study.