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 .
Effect of evolocumab or ezetimibe added to moderate- or high-intensity statin therapy on LDL-C lowering in patients with hypercholesterolemia: the LAPLACE-2 randomized clinical trial.
IMPORTANCE In phase 2 studies , evolocumab , a fully human monoclonal antibody to PCSK9 , reduced LDL-C levels in patients receiving statin therapy . OBJECTIVE To evaluate the efficacy and tolerability of evolocumab when used in combination with a moderate- vs high-intensity statin . DESIGN , SETTING , AND PATIENTS Phase 3 , 12-week , r and omized , double-blind , placebo- and ezetimibe-controlled study conducted between January and December of 2013 in patients with primary hypercholesterolemia and mixed dyslipidemia at 198 sites in 17 countries . INTERVENTIONS Patients ( n = 2067 ) were r and omized to 1 of 24 treatment groups in 2 steps . Patients were initially r and omized to a daily , moderate-intensity ( atorvastatin [ 10 mg ] , simvastatin [ 40 mg ] , or rosuvastatin [ 5 mg ] ) or high-intensity ( atorvastatin [ 80 mg ] , rosuvastatin [ 40 mg ] ) statin . After a 4-week lipid-stabilization period , patients ( n = 1899 ) were r and omized to compare evolocumab ( 140 mg every 2 weeks or 420 mg monthly ) with placebo ( every 2 weeks or monthly ) or ezetimibe ( 10 mg or placebo daily ; atorvastatin patients only ) when added to statin therapies . MAIN OUTCOMES AND MEASURES Percent change from baseline in low-density lipoprotein cholesterol ( LDL-C ) level at the mean of weeks 10 and 12 and at week 12 . RESULTS Evolocumab  reduced LDL-C levels by 66 % ( 95 % CI , 58 % to 73 % ) to 75 % ( 95 % CI , 65 % to 84 % ) ( every 2 weeks ) and by 63 % ( 95 % CI , 54 % to 71 % ) to 75 % ( 95 % CI , 67 % to 83 % ) ( monthly ) vs placebo at the mean of weeks 10 and 12 in the moderate- and high-intensity statin-treated groups ; the LDL-C reductions at week 12 were comparable . For moderate-intensity statin groups , evolocumab every 2 weeks reduced LDL-C from a baseline mean of 115 to 124 mg/dL to an on-treatment mean of 39 to 49 mg/dL ; monthly evolocumab reduced LDL-C from a baseline mean of 123 to 126 mg/dL to an on-treatment mean of 43 to 48 mg/dL. For high-intensity statin groups , evolocumab every 2 weeks reduced LDL-C from a baseline mean of 89 to 94 mg/dL to an on-treatment mean of 35 to 38 mg/dL ; monthly evolocumab reduced LDL-C from a baseline mean of 89 to 94 mg/dL to an on-treatment mean of 33 to 35 mg/dL. Adverse events were reported in 36 % , 40 % , and 39 % of evolocumab- , ezetimibe- , and placebo-treated patients , respectively . The most common adverse events in evolocumab-treated patients were back pain , arthralgia , headache , muscle spasms , and pain in extremity ( all < 2 % ) . CONCLUSIONS AND RELEVANCE In this 12-week trial conducted among patients with primary hypercholesterolemia and mixed dyslipidemia , evolocumab added to moderate- or high-intensity statin therapy result ed in additional LDL-C lowering . Further studies are needed to evaluate the longer-term clinical outcomes and safety of this approach for LDL-C lowering . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01763866
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 .