The reduction in MACEs was observed in White but not in Asian subjects .
Both alirocumab and evolocumab are well tolerated and can greatly improve lipid profiles for patients at high cardiovascular risk .
Both PCSK9 monoclonal antibodies significantly reduce the risk of nonfatal MACEs in patients with previous cardiovascular events , but the effect on all-cause mortality remains uncertain
Proprotein convertase subtilisin/kexin type 9 ( PCSK9 ) monoclonal antibodies are powerful lipid-lowering drugs which have been shown to improve clinical endpoints in patients with hypercholesterolemia .
However , it is not clear how effective PCSK9 monoclonal antibodies are for patients at high cardiovascular risk .
Also , whether the effectiveness of PCSK9 monoclonal antibodies varies between different drug types , dosages , race , and indications for PCSK9 monoclonal antibodies remains unclear .
Therefore , we used recently published studies to systematic ally evaluate the efficacy and safety of PCSK9 monoclonal antibodies by analyzing the lipid profiles , adverse events , and clinical endpoints in patients at high cardiovascular risk .
Lipid‐Reduction Variability and Antidrug‐Antibody Formation with Bococizumab
BACKGROUND Bococizumab , a humanized monoclonal antibody targeting proprotein convertase subtilisin – kexin type 9 ( PCSK9 ) , reduces levels of low‐density lipoprotein ( LDL ) cholesterol . However , the variability and durability of this effect are uncertain . METHODS We conducted six parallel , multinational lipid‐lowering trials enrolling 4300 patients with hyperlipidemia who were r and omly assigned to receive 150 mg of bococizumab or placebo subcutaneously every 2 weeks and who were followed for up to 12 months ; 96 % were receiving statin therapy at the time of enrollment . The patients were assessed for lipid changes over time , stratified according to the presence or absence of antidrug antibodies detected during the treatment period . RESULTS At 12 weeks , patients who received bococizumab had a reduction of 54.2 % in the LDL cholesterol level from baseline , as compared with an increase of 1.0 % among those who received placebo ( absolute between‐group difference , ‐55.2 percentage points ) . Significant between‐group differences were also observed in total cholesterol , non – high‐density lipoprotein cholesterol , apolipoprotein B , and lipoprotein(a ) ( P<0.001 for all comparisons ) . However , high‐titer antidrug antibodies developed in a substantial proportion of the patients who received bococizumab , which markedly diminished the magnitude and durability of the reduction in LDL cholesterol levels . In addition , among patients with no antidrug antibodies , there was wide variability in the reduction in LDL cholesterol levels at both 12 weeks and 52 weeks . Major cardiovascular events occurred in 57 patients ( 2.5 % ) who received bococizumab and in 55 ( 2.7 % ) who received placebo ( hazard ratio , 0.96 ; 95 % confidence interval , 0.66 to 1.39 ; P=0.83 ) . The most common adverse event among patients who received bococizumab was injection‐site reaction ( 12.7 per 100 person‐years ) . CONCLUSIONS In six multinational trials evaluating bococizumab , antidrug antibodies developed in a large proportion of the patients and significantly attenuated the lowering of LDL cholesterol levels . Wide variation in the relative reduction in cholesterol levels was also observed among patients in whom antidrug antibodies did not develop . ( Funded by Pfizer ; SPIRE Clinical Trials.gov numbers , NCT01968954 , NCT01968967 , NCT01968980 , NCT02100514 , NCT02135029 , and NCT02458287 .
The reduction in MACEs was observed in White but not in Asian subjects .
Both alirocumab and evolocumab are well tolerated and can greatly improve lipid profiles for patients at high cardiovascular risk .
Both PCSK9 monoclonal antibodies significantly reduce the risk of nonfatal MACEs in patients with previous cardiovascular events , but the effect on all-cause mortality remains uncertain
Proprotein convertase subtilisin/kexin type 9 ( PCSK9 ) monoclonal antibodies are powerful lipid-lowering drugs which have been shown to improve clinical endpoints in patients with hypercholesterolemia .
However , it is not clear how effective PCSK9 monoclonal antibodies are for patients at high cardiovascular risk .
Also , whether the effectiveness of PCSK9 monoclonal antibodies varies between different drug types , dosages , race , and indications for PCSK9 monoclonal antibodies remains unclear .
Therefore , we used recently published studies to systematic ally evaluate the efficacy and safety of PCSK9 monoclonal antibodies by analyzing the lipid profiles , adverse events , and clinical endpoints in patients at high cardiovascular risk .