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 and Safety of Alirocumab in Japanese Subjects (Phase 1 and 2 Studies).
We assessed the safety and tolerability of ascending single doses of alirocumab in healthy Japanese subjects and evaluated the effect of alirocumab at 3 doses ( 50 , 75 , 150 mg ) on low-density lipoprotein cholesterol ( LDL-C ) reduction in patients with primary hypercholesterolemia on atorvastatin . A r and omized , single ascending-dose study of alirocumab ( 100 , 150 , 250 , or 300 mg ) or placebo ( 3:1 ratio ) , administered subcutaneously , was conducted in 32 healthy Japanese men . The phase 2 , r and omized , double-blind , placebo-controlled , parallel-group study was performed in patients with primary hypercholesterolemia ( defined as calculated LDL-C ≥100 mg/dl [ 2.6 mmol/l ] ) who were on a stable dose of atorvastatin ( 5 to 20 mg ) . Patients were r and omized to alirocumab ( 50 , 75 , or 150 mg ) or placebo ( in single 1.0-ml injection volumes ) administered every 2 weeks ( Q2W ) for 12 weeks ; the primary outcome was the mean percent change in calculated LDL-C from baseline to week 12 . Single subcutaneous administration of alirocumab in healthy subjects was well tolerated over 15 weeks and result ed in highest mean percent reductions in LDL-C from baseline of approximately 40 % to 60 % . In the multiple-dose study , least-square mean ( SE ) changes in calculated LDL-C concentrations from baseline to week 12 were -54.8 % ( 3.1 % ) for alirocumab 50 mg , -62.3 % ( 3.1 % ) for alirocumab 75 mg , and -71.7 % ( 3.1 % ) for alirocumab 150 mg , with a least-square mean ( SE ) difference versus placebo of -52.2 % ( 4.3 % ) , -59.6 % ( 4.3 % ) , and -69.1 % ( 4.3 % ) , respectively ( all p < 0.0001 ) . In conclusion , alirocumab was well tolerated and significantly reduced LDL-C concentrations in Japanese patients with primary hypercholesterolemia on atorvastatin
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 .