Treatment with a PCSK9 inhibitor is well tolerated and improves cardiovascular outcomes .
Although no overall benefit was noted in all-cause or cardiovascular mortality , such benefit may be achievable in patients with higher baseline low-density lipoprotein cholesterol
BACKGROUND We sought to examine the efficacy and safety of 2 PCSK9 ( proprotein convertase subtilisin/kexin type 9 ) inhibitors : alirocumab and evolocumab .
Effects of evolocumab (AMG 145), a monoclonal antibody to PCSK9, in hypercholesterolemic, statin-treated Japanese patients at high cardiovascular risk--primary results from the phase 2 YUKAWA study.
BACKGROUND YUKAWA is a 12-week , r and omized , double-blind , placebo-controlled , phase 2 study evaluating the efficacy and safety of evolocumab ( AMG 145 ) in statin-treated Japanese patients at high cardiovascular risk . METHODS AND RESULTS 310 eligible patients receiving stable statin ( ±ezetimibe ) therapy were r and omized to 1 of 6 treatments : placebo every 2 weeks ( Q2W ) or monthly ( QM ) , evolocumab 70 mg or 140 mg Q2W , or evolocumab 280 mg or 420 mg QM . The primary endpoint was the percentage change from baseline in low-density lipoprotein cholesterol ( LDL-C ) measured by preparative ultracentrifugation ( UC ) . Secondary endpoints included percentage changes in other lipid parameters and the proportion of patients with LDL-C < 1.8 mmol/L.  Mean ( SD ) age was 62 ( 10 ) years ; 37 % were female ; and the mean ( SD ) baseline LDL-C was 3.7 ( 0.5 ) mmol/L ( by UC ) . Mean ( SE ) changes vs. placebo in LDL-C were greatest in the high-dose groups : -68.6 ( 3.0 ) % and -63.9 ( 3.2 ) % with 140 mg Q2W and 420 mg QM dosing , respectively . Up to 96 % of evolocumab-treated patients achieved LDL-C < 1.8 mmol/L. Adverse events ( AEs ) were more frequent in evolocumab ( 51 % ) vs. placebo ( 38 % ) patients ; 4 patients taking evolocumab discontinued treatment because of an AE . There were no significant differences in AE rates based on dose or dose frequency . CONCLUSIONS In Japanese patients at high cardiovascular risk with hypercholesterolemia on stable statin therapy , evolocumab  significantly reduced LDL-C and was well tolerated during this 12-week study
Treatment with a PCSK9 inhibitor is well tolerated and improves cardiovascular outcomes .
Although no overall benefit was noted in all-cause or cardiovascular mortality , such benefit may be achievable in patients with higher baseline low-density lipoprotein cholesterol
BACKGROUND We sought to examine the efficacy and safety of 2 PCSK9 ( proprotein convertase subtilisin/kexin type 9 ) inhibitors : alirocumab and evolocumab .