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 .
Efficacy, safety, and tolerability of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 in combination with a statin in patients with hypercholesterolaemia (LAPLACE-TIMI 57): a randomised, placebo-controlled, dose-ranging, phase 2 study
BACKGROUND LDL cholesterol ( LDL-C ) is a well established risk factor for cardiovascular disease . Proprotein convertase subtilisin/kexin type 9 ( PCSK9 ) binds LDL receptors , targeting them for degradation . We therefore assessed the efficacy , safety , and tolerability of AMG 145 , a human monoclonal IgG2 antibody against PCSK9 , in stable patients with hypercholesterolemia on a statin . METHODS In a phase 2 , dose-ranging study done in 78 centres in the USA , Canada , Denmark , Hungary , and Czech Republic , patients ( aged 18 - 80 years ) with LDL-C greater than 2·2 mmol/L on a stable dose of statin ( with or without ezetimibe )  , were r and omly assigned equally , through an interactive voice response system , to subcutaneous injections of AMG 145 70 mg , 105 mg , or 140 mg , or matching placebo every 2 weeks ; or subcutaneous injections of AMG 145 280 mg , 350 mg , or 420 mg , or matching placebo every 4 weeks . Everyone was masked to treatment assignment within the every 2 weeks and every 4 weeks schedules . The primary endpoint was the percentage change in LDL-C concentration from baseline after 12 weeks . Analysis was by modified intention to treat . This study is registered with Clinical Trials.gov , number NCT01380730 . FINDINGS 631 patients with hypercholesterolaemia were r and omly assigned to AMG 145 70 mg ( n=79 ) , 105 mg ( n=79 ) , or 140 mg ( n=78 ) , or matching placebo ( n=78 ) every 2 weeks ; or AMG 145 280 mg ( n=79 ) , 350 mg ( n=79 ) , and 420 mg ( n=80 ) , and matching placebo ( n=79 ) every 4 weeks . At the end of the dosing interval at week 12 , the mean LDL-C concentrations were reduced generally dose dependently by AMG 145 every 2 weeks ( ranging from 41·8 % to 66·1 % ; p<0·0001 for each dose vs placebo ) and AMG 145 every 4 weeks ( ranging from 41·8 % to 50·3 % ; p<0·0001 ) . No treatment-related serious adverse events occurred . The frequencies of treatment-related adverse events were similar in the AMG 145 and placebo groups ( 39 [ 8 % ] of 474 vs 11 [ 7 % ] of 155 ) ; none of these events were severe or life-threatening . INTERPRETATION The results suggest that PCSK9 inhibition could be a new model in lipid management . Inhibition of PCSK9 warrants assessment in phase 3 clinical trials . FUNDING Amgen
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 .