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 .
Cardiovascular benefits and diabetes risks of statin therapy in primary prevention: an analysis from the JUPITER trial
BACKGROUND In view of evidence that statin therapy increases risk of diabetes , the balance of benefit and risk of these drugs in primary prevention has become controversial . We undertook an analysis of participants from the JUPITER trial to address the balance of vascular benefits and diabetes hazard of statin use . METHODS In the r and omised , double-blind JUPITER trial , 17,603 men and women without previous cardiovascular disease or diabetes were r and omly assigned to rosuvastatin 20 mg or placebo and followed up for up to 5 years for the primary endpoint ( myocardial infa rct ion , stroke , admission to hospital for unstable angina , arterial revascularisation , or cardiovascular death ) and the protocol -prespecified secondary endpoints of venous thromboembolism , all-cause mortality , and incident physician-reported diabetes . In this analysis , participants were stratified on the basis of having none or at least one of four major risk factors for developing diabetes : metabolic syndrome , impaired fasting glucose , body-mass index 30 kg/m(2 ) or higher , or glycated haemoglobin A(1c ) greater than 6 % . The trial is registered at Clinical Trials.gov , NCT00239681 . FINDINGS Trial participants with one or more major diabetes risk factor ( n=11,508 ) were at higher risk of developing diabetes than were those without a major risk factor ( n=6095 ) . In individuals with one or more risk factors , statin allocation was associated with a 39 % reduction in the primary endpoint ( hazard ratio [ HR ] 0·61 , 95 % CI 0·47 - 0·79 , p=0·0001 ) , a 36 % reduction in venous thromboembolism ( 0·64 , 0·39 - 1·06 , p=0·08 ) , a 17 % reduction in total mortality ( 0·83 , 0·64 - 1·07 , p=0·15 ) , and a 28 % increase in diabetes ( 1·28 , 1·07 - 1·54 , p=0·01 ) . Thus , for those with diabetes risk factors , a total of 134 vascular events or deaths were avoided for every 54 new cases of diabetes diagnosed . For trial participants with no major diabetes risk factors  , statin allocation was associated with a 52 % reduction in the primary endpoint ( HR 0·48 , 95 % CI 0·33 - 0·68 , p=0·0001 ) , a 53 % reduction in venous thromboembolism ( 0·47 , 0·21 - 1·03 , p=0·05 ) , a 22 % reduction in total mortality ( 0·78 , 0·59 - 1·03 , p=0·08 ) , and no increase in diabetes ( 0·99 , 0·45 - 2·21 , p=0·99 ) . For such individuals , a total of 86 vascular events or deaths were avoided with no new cases of diabetes diagnosed . In analysis limited to the 486 participants who developed diabetes during follow-up ( 270 on rosuvastatin vs 216 on placebo ; HR 1·25 , 95 % CI 1·05 - 1·49 , p=0·01 ) , the point estimate of cardiovascular risk reduction  associated with statin therapy ( HR 0·63 , 95 % CI 0·25 - 1·60 ) was consistent with that for the trial as a whole ( 0·56 , 0·46 - 0·69 ) . By comparison with placebo , statins  accelerated the average time to diagnosis of diabetes by 5·4 weeks ( 84·3 [ SD 47·8 ] weeks on rosuvastatin vs 89·7 [ 50·4 ] weeks on placebo ) . INTERPRETATION In the JUPITER primary prevention trial , the cardiovascular and mortality benefits  of statin therapy exceed the diabetes hazard , including in participants at high risk of developing diabetes . FUNDING AstraZeneca
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 .