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 .
Low-Density Lipoprotein Cholesterol–Lowering Effects of AMG 145, a Monoclonal Antibody to Proprotein Convertase Subtilisin/Kexin Type 9 Serine Protease in Patients With Heterozygous Familial Hypercholesterolemia: The Reduction of LDL-C With PCSK9 Inhibition in Heterozygous Familial Hypercholesterole
Background — Despite statin treatment , many patients with heterozygous familial hypercholesterolemia do not reach desired low-density lipoprotein cholesterol ( LDL-C ) targets . AMG 145 , a fully human monoclonal antibody against proprotein convertase subtilisin/kexin type 9 ( PCSK9 ) serine protease , demonstrated significant reductions in LDL-C in phase 1 studies . This phase 2 , multicenter , double-blind , r and omized , placebo-controlled , dose-ranging study evaluated the efficacy and safety of AMG 145 in heterozygous familial hypercholesterolemia patients . Methods and Results — Patients with heterozygous familial hypercholesterolemia diagnosed by Simon Broome criteria with LDL-C ≥2.6 mmol/L ( 100 mg/dL ) despite statin therapy with or without ezetimibe  were r and omized 1:1:1 to AMG 145 350 mg , AMG 145 420 mg , or placebo-administered subcutaneously every 4 weeks . The primary end point was percentage change from baseline in LDL-C at week 12 . Of 168 patients r and omized , 167 received investigational product and were included in the full analysis set ( mean [ SD ] age , 50 [ 13 ] years ; 47 % female ; 89 % white ; mean [ SD ] baseline LDL-C , 4.0 [ 1.1 ] mmol/L ( 156 [ 42 ] mg/dL ) ) . At week 12 , LDL-C reduction measured by preparative ultracentrifugation ( least squares mean [ st and ard error ( SE ) ] ) was 43 (3)% and 55 (3)% with AMG 145 350 mg and 420 mg , respectively , compared with 1 (3)% increase with placebo ( P<0.001 for both dose groups ) . Serious adverse events ( not considered treatment-related ) occurred in 2 patients on AMG 145 . Conclusions — AMG 145 administered every 4 weeks yielded rapid and substantial reductions in LDL-C in heterozygous familial hypercholesterolemia patients despite intensive statin use , with or without ezetimibe , with minimal adverse events and good tolerability . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT01375751
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 .