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 .
Cardiovascular Efficacy and Safety of Bococizumab in High‐Risk Patients
BACKGROUND Bococizumab is a humanized monoclonal antibody that inhibits proprotein convertase subtilisin – kexin type 9 ( PCSK9 ) and reduces levels of low‐density lipoprotein ( LDL ) cholesterol . We sought to evaluate the efficacy of bococizumab in patients at high cardiovascular risk . METHODS In two parallel , multinational trials with different entry criteria for LDL cholesterol levels , we r and omly assigned the 27,438 patients in the combined trials to receive bococizumab ( at a dose of 150 mg ) subcutaneously every 2 weeks or placebo . The primary end point was nonfatal myocardial infa rct ion , nonfatal stroke , hospitalization for unstable angina requiring urgent revascularization , or cardiovascular death ; 93 % of the patients were receiving statin therapy at baseline . The trials were stopped early after the sponsor elected to discontinue the development of bococizumab owing in part to the development of high rates of antidrug antibodies , as seen in data from other studies in the program . The median follow‐up was 10 months . RESULTS At 14 weeks , patients in the combined trials had a mean change from baseline in LDL cholesterol levels of ‐56.0 % in the bococizumab group and + 2.9 % in the placebo group , for a between‐group difference of –59.0 percentage points ( P<0.001 ) and a median reduction from baseline of 64.2 % ( P<0.001 ) . In the lower‐risk , shorter‐ duration trial ( in which the patients had a baseline LDL cholesterol level of ≥70 mg per deciliter [ 1.8 mmol per liter ] and the median follow‐up was 7 months ) , major cardiovascular events occurred in 173 patients each in the bococizumab group and the placebo group ( hazard ratio , 0.99 ; 95 % confidence interval [ CI ] , 0.80 to 1.22 ; P=0.94 ) . In the higher‐risk , longer‐ duration trial ( in which the patients had a baseline LDL cholesterol level of ≥100 mg per deciliter [ 2.6 mmol per liter ] and the median follow‐up was 12 months ) , major cardiovascular events occurred in 179 and 224 patients , respectively ( hazard ratio , 0.79 ; 95 % CI , 0.65 to 0.97 ; P=0.02 ) . The hazard ratio for the primary end point in the combined trials was 0.88 ( 95 % CI , 0.76 to 1.02 ; P=0.08 ) . Injection‐site reactions were more common in the bococizumab group than in the placebo group ( 10.4 % vs. 1.3 % , P<0.001 ) . CONCLUSIONS In two r and omized trials comparing the PCSK9 inhibitor bococizumab with placebo , bococizumab had no benefit with respect to major adverse cardiovascular events in the trial involving lower‐risk patients but did have a significant benefit in the trial involving higher‐risk patients . ( Funded by Pfizer ; SPIRE‐1 and SPIRE‐2 Clinical Trials.gov numbers , NCT01975376 and NCT01975389 .
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 .