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 .
Variation in PCSK9 and HMGCR and Risk of Cardiovascular Disease and Diabetes.
BACKGROUND Pharmacologic inhibitors of proprotein convertase subtilisin-kexin type 9 ( PCSK9 ) are being evaluated in clinical trials for the treatment of cardiovascular disease . The effect of lowering low-density lipoprotein ( LDL ) cholesterol levels by inhibiting PCSK9 on the risk of cardiovascular events or diabetes is unknown . METHODS We used genetic scores consisting of independently inherited variants in the genes encoding PCSK9 and 3-hydroxy-3-methylglutaryl-coenzyme A reductase ( HMGCR ; the target of statins ) as instruments to r and omly assign 112,772 participants from 14 studies , with 14,120 cardiovascular events and 10,635 cases of diabetes , to groups according to the number of LDL cholesterol-lowering alleles that they had inherited . We compared the effects of lower LDL cholesterol levels that were mediated by variants in PCSK9 , HMGCR , or both on the risk of cardiovascular events and the risk of diabetes . RESULTS Variants in PCSK9 and HMGCR were associated with nearly identical protective effects on the risk of cardiovascular events per decrease of 10 mg per deciliter ( 0.26 mmol per liter ) in the LDL cholesterol level : odds ratio for cardiovascular events , 0.81 ( 95 % confidence interval [ CI ] , 0.74 to 0.89 ) for PCSK9 and 0.81 ( 95 % CI , 0.72 to 0.90 ) for HMGCR . Variants in these two genes were also associated with very similar effects on the risk of diabetes : odds ratio for each 10 mg per deciliter decrease in LDL cholesterol , 1.11 ( 95 % CI , 1.04 to 1.19 ) for PCSK9 and 1.13 ( 95 % CI , 1.06 to 1.20 ) for HMGCR . The increased risk of diabetes was limited to persons with impaired fasting glucose levels for both scores and was lower in magnitude than the protective effect against cardiovascular events . When present together , PCSK9 and HMGCR variants had additive effects on the risk of both cardiovascular events and diabetes . CONCLUSIONS In this study , variants in PCSK9 had approximately the same effect as variants in HMGCR on the risk of cardiovascular events and diabetes per unit decrease in the LDL cholesterol level . The effects of these variants were independent and additive . ( Funded by the Medical Research Council and the National Heart , Lung , and Blood Institute . )
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 .