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 .
A 52-week placebo-controlled trial of evolocumab in hyperlipidemia.
BACKGROUND Evolocumab , a monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 ( PCSK9 ) , significantly reduced low-density lipoprotein ( LDL ) cholesterol levels in phase 2 studies . We conducted a phase 3 trial to evaluate the safety and efficacy of 52 weeks of treatment with evolocumab . METHODS We stratified patients with hyperlipidemia according to the risk categories outlined by the Adult Treatment Panel III of the National Cholesterol Education Program . On the basis of this classification , patients were started on background lipid-lowering therapy with diet alone or diet plus atorvastatin at a dose of 10 mg daily , atorvastatin at a dose of 80 mg daily , or atorvastatin at a dose of 80 mg daily plus ezetimibe at a dose of 10 mg daily , for a run-in period of 4 to 12 weeks . Patients with an LDL cholesterol level of 75 mg per deciliter ( 1.9 mmol per liter ) or higher were then r and omly assigned in a 2:1 ratio to receive either evolocumab ( 420 mg ) or placebo every 4 weeks . The primary end point was the percent change from baseline in LDL cholesterol , as measured by means of ultracentrifugation , at week 52 . RESULTS Among the 901 patients included in the primary analysis , the overall least-squares mean ( ±SE ) reduction in LDL cholesterol from baseline in the evolocumab group , taking into account the change in the placebo group , was 57.0±2.1 % ( P<0.001 ) . The mean reduction was 55.7±4.2 % among patients who underwent background therapy with diet alone , 61.6±2.6 % among those who received 10 mg of atorvastatin , 56.8±5.3 % among those who received 80 mg of atorvastatin , and 48.5±5.2 % among those who received a combination of 80 mg of atorvastatin and 10 mg of ezetimibe ( P<0.001 for all comparisons ) . Evolocumab treatment also significantly reduced levels of apolipoprotein B , non-high-density lipoprotein cholesterol , lipoprotein(a ) , and triglycerides . The most common adverse events were nasopharyngitis , upper respiratory tract infection , influenza , and back pain . CONCLUSIONS At 52 weeks , evolocumab added to diet alone , to low-dose atorvastatin , or to high-dose atorvastatin with or without ezetimibe significantly reduced LDL cholesterol levels in patients with a range of  cardiovascular risks . ( Funded by Amgen ; DESCARTES Clinical Trials.gov number , NCT01516879 . )
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 .