Anti-PCSK9 antibodies for hypercholesterolaemia: Overview of clinical data and implications for primary care.

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Term Occurence Count Dictionary
Evolocumab 18 endocrinologydiseasesdrugs
atorvastatin 30 endocrinologydiseasesdrugs
ezetimibe 39 endocrinologydiseasesdrugs
type 2 diabetes mellitus 13 endocrinologydiseases
Alirocumab 19 endocrinologydiseasesdrugs
diabetes mellitus 17 endocrinologydiseases
fenofibrate 1 endocrinologydiseasesdrugs
rosuvastatin 14 endocrinologydiseasesdrugs
simvastatin 11 endocrinologydiseasesdrugs

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Select Drug Character Offset Drug Term Instance
Alirocumab 18894 therapy (all treatment arms)Anti‐PCSK9 antibody groupComparator groupHeterozygous FHODYSSEY FH I30 Alirocumab 75 mg Q2W: 72.2%Placebo: 2.4%78 82.7%‐85.3% received high‐intensity statin therapy (atorvastatin
Alirocumab 19126 rosuvastatin 20‐40 mg QD or simvastatin 80 mg QD) 56.0%‐59.5% received ezetimibe ODYSSEY FH II 30 Alirocumab 75 mg Q2W: 81.4%Placebo: 11.3%78 86.8%‐91.5% received high‐intensity statin therapy (atorvastatin
Alirocumab 19362 rosuvastatin 20‐40 mg QD or simvastatin 80 mg QD) 64.6%‐67.1% received ezetimibe ODYSSEY HIGH FH54,a Alirocumab 150 mg Q2W: 41.0%Placebo: 5.7%24100% received maximally tolerated statin ± other LLTRUTHERFORD‐240 Evolocumab
Alirocumab 21233 80 mg QD + ezetimibe 10 mg: 11.1% Overall: 6.4% 52NoneModerate‐to‐very high CV riskODYSSEY MONO34,c Alirocumab 75 mg Q2W (up titrated to 150 mg Q2W): 65.0%Ezetimibe: 10 mg QD: 2%‐3%24NoneODYSSEY CHOICE I35,d Alirocumab
Alirocumab 21346 75 mg Q2W (up titrated to 150 mg Q2W): 65.0%Ezetimibe: 10 mg QD: 2%‐3%24NoneODYSSEY CHOICE I35,d Alirocumab 300 mg Q4W: 78.9% Alirocumab 300 mg Q4W + statin: 85.2% Alirocumab 75 mg Q2W: 84.9% Alirocumab 75 mg
Alirocumab 21376 150 mg Q2W): 65.0%Ezetimibe: 10 mg QD: 2%‐3%24NoneODYSSEY CHOICE I35,d Alirocumab 300 mg Q4W: 78.9% Alirocumab 300 mg Q4W + statin: 85.2% Alirocumab 75 mg Q2W: 84.9% Alirocumab 75 mg Q2W + statin: 82.5% Placebo:
Alirocumab 21415 2%‐3%24NoneODYSSEY CHOICE I35,d Alirocumab 300 mg Q4W: 78.9% Alirocumab 300 mg Q4W + statin: 85.2% Alirocumab 75 mg Q2W: 84.9% Alirocumab 75 mg Q2W + statin: 82.5% Placebo: 9.4% Placebo + statin: 22.2% 24 No
Alirocumab 21444 I35,d Alirocumab 300 mg Q4W: 78.9% Alirocumab 300 mg Q4W + statin: 85.2% Alirocumab 75 mg Q2W: 84.9% Alirocumab 75 mg Q2W + statin: 82.5% Placebo: 9.4% Placebo + statin: 22.2% 24 No statin group: 0–1.4% received
Alirocumab 21768 received atorvastatin, rosuvastatin or simvastatin 32.4%‐45.2% received other LLT ODYSSEY CHOICE II81,d Alirocumab 150 mg Q4W: 63.9% Alirocumab 75 mg Q2W: 70.3% Placebo Q2W: 1.8%24 30.2%‐34.5% received diet alone 59.3%‐60.3%
Alirocumab 21798 or simvastatin 32.4%‐45.2% received other LLT ODYSSEY CHOICE II81,d Alirocumab 150 mg Q4W: 63.9% Alirocumab 75 mg Q2W: 70.3% Placebo Q2W: 1.8%24 30.2%‐34.5% received diet alone 59.3%‐60.3% received ezetimibe 5.2%‐10.3%
Alirocumab 21979 alone 59.3%‐60.3% received ezetimibe 5.2%‐10.3% received fenofibrate High CV riskODYSSEY COMBO I31,e Alirocumab 75 mg Q2W: 75.0%Placebo: 9%24 99.5–100% received statins (high dose: 61.7%‐64.5%; atorvastatin
Alirocumab 22248 simvastatin 80 mg QD) 7.2%‐10.3% received ezetimibe 38.3%‐49.5% received other LLT ODYSSEY COMBO II 28,f Alirocumab 75 mg Q2W: 77.0%Ezetimibe 10 mg QD: 45.6%24 99.8%‐100% received statins 66.4%‐66.8% received high‐intensity
Alirocumab 22476 statin therapy (atorvastatin 40‐80 mg QD or rosuvastatin 20‐40 mg QD) ODYSSEY LONG TERM 33,f,g Alirocumab 150 mg Q2W (high or very high risk): 80.7% Regardless of risk: 79.3% Placebo: (high or very high risk):8.5% Regardless
Alirocumab 23552 received statins (atorvastatin 5 mg or 20 mg QD)High‐to‐very high CV riskODYSSEY OPTIONS I 27,i Alirocumab 75 mg Q2W + atorvastatin 20/40 mg QD: 84.6%‐87.2% Ezetimibe 10 mg QD + atorvastatin 20/40 mg QD:
Alirocumab 23831 40/80 mg QD: 18.5%‐34.5% 24100% received statins (atorvastatin 20 mg or 40 mg QD)ODYSSEY OPTIONS II29,i Alirocumab 75 mg Q2W + rosuvastatin 10/20 mg QD: 66.7%‐84.9% Ezetimibe 10 mg QD + rosuvastatin 10/20 mg QD:
Alirocumab 24097 29.9%‐45.0% 24100% received statins (rosuvastatin 10 mg or 20 mg QD)Statin intolerantODYSSEY ALTERNATIVE 32 Alirocumab 75 mg Q2W (up titrated to 150 mg Q2W): 41.9%‐51.2% Ezetimibe 10 mg QD: 4.4%‐5.6% Atorvastatin
Alirocumab 42566 2Observed and predicted reductions in cardiovascular events in ODYSSEY LONG TERM and OSLER‐1 and ‐2 Alirocumab EvolocumabStudyODYSSEY LONG TERM33OSLER‐1 and ‐241Number of patients2341 (1553 alirocumab/788 placebo)4465
Alirocumab 54138 PCSK9, proprotein convertase subtilisin/kexin type 9Approved indications for alirocumab and evolocumab3.6 Alirocumab and evolocumab have both been approved in Europe for use as an adjunct to diet in adults with primary
Alirocumab 54566 approved for use in combination with other LLTs in patients aged 12 years and older who have HoFH.15 Alirocumab is administered subcutaneously at a recommended starting dose of 75 mg once every 2 weeks or 300 mg
Evolocumab 12257 LDL‐C reductions ranged from 45.7% to 57.9% with alirocumab, and from 55.7% to 61.3% with evolocumab.18 Evolocumab has been investigated in patients with homozygous familial hypercholesterolaemia (HoFH), but alirocumab
Evolocumab 19476 150 mg Q2W: 41.0%Placebo: 5.7%24100% received maximally tolerated statin ± other LLTRUTHERFORD‐240 Evolocumab 140 mg Q2W: 68.0% Evolocumab 420 mg QM: 63.0% Placebo: 2%12 100% received statins: 87% received high‐intensity
Evolocumab 19506 5.7%24100% received maximally tolerated statin ± other LLTRUTHERFORD‐240 Evolocumab 140 mg Q2W: 68.0% Evolocumab 420 mg QM: 63.0% Placebo: 2%12 100% received statins: 87% received high‐intensity statin (simvastatin
Evolocumab 19825 ezetimibe) 62% received ezetimibe Type 2 diabetes mellitusPooled meta‐analysis of four studies45, 79 Evolocumab 140 mg Q2W: 88.0% Evolocumab 420 mg Q4W: 87.0% Ezetimibe 10 mg + placebo Q2W: 36.0% Ezetimibe 10 mg
Evolocumab 19855 ezetimibe Type 2 diabetes mellitusPooled meta‐analysis of four studies45, 79 Evolocumab 140 mg Q2W: 88.0% Evolocumab 420 mg Q4W: 87.0% Ezetimibe 10 mg + placebo Q2W: 36.0% Ezetimibe 10 mg + placebo QM: 29.0% Placebo
Evolocumab 20614 QD GAUSS‐242: 33% received LLT, 18% received low‐dose statin therapy Low‐to‐high CV riskDESCARTES36,b Evolocumab 420 mg Q4W + diet + background LLT: 83.6% Evolocumab 420 mg Q4W + diet + atorvastatin 10 mg QD: 90.1% Evolocumab
Evolocumab 20667 statin therapy Low‐to‐high CV riskDESCARTES36,b Evolocumab 420 mg Q4W + diet + background LLT: 83.6% Evolocumab 420 mg Q4W + diet + atorvastatin 10 mg QD: 90.1% Evolocumab 420 mg Q4W + diet + atorvastatin 80 mg
Evolocumab 20728 mg Q4W + diet + background LLT: 83.6% Evolocumab 420 mg Q4W + diet + atorvastatin 10 mg QD: 90.1% Evolocumab 420 mg Q4W + diet + atorvastatin 80 mg QD: 80.8% Evolocumab 420 mg Q4W + diet + atorvastatin 80 mg
Evolocumab 20789 + diet + atorvastatin 10 mg QD: 90.1% Evolocumab 420 mg Q4W + diet + atorvastatin 80 mg QD: 80.8% Evolocumab 420 mg Q4W + diet + atorvastatin 80 mg QD + ezetimibe 10 mg QD: 67.0% Overall: 82.3%Goal defined as
Evolocumab 22941 simvastatin 80 mg QD) 13.9%‐15.0% received ezetimibe 27.9%‐28.1% received other LLT YUKAWA‐237,h Evolocumab 140 mg Q2W + atorvastatin 5 mg QD: 98.0%‐100% Evolocumab 420 QM + atorvastatin 5 mg QD: 96.0%‐100% Evolocumab
Evolocumab 23002 ezetimibe 27.9%‐28.1% received other LLT YUKAWA‐237,h Evolocumab 140 mg Q2W + atorvastatin 5 mg QD: 98.0%‐100% Evolocumab 420 QM + atorvastatin 5 mg QD: 96.0%‐100% Evolocumab 140 Q2W + atorvastatin 20 mg QD: 96.0%‐100% Evolocumab
Evolocumab 23058 140 mg Q2W + atorvastatin 5 mg QD: 98.0%‐100% Evolocumab 420 QM + atorvastatin 5 mg QD: 96.0%‐100% Evolocumab 140 Q2W + atorvastatin 20 mg QD: 96.0%‐100% Evolocumab 420 mg QM + atorvastatin 20 mg QD: 98.0%‐100%Goal
Evolocumab 23116 QM + atorvastatin 5 mg QD: 96.0%‐100% Evolocumab 140 Q2W + atorvastatin 20 mg QD: 96.0%‐100% Evolocumab 420 mg QM + atorvastatin 20 mg QD: 98.0%‐100%Goal defined as LDL‐C <70 mg/dL (<1.8 mmol/L) for
Evolocumab 24382 statins 32.5%‐49.2% received LLT other than nutraceuticals 5.6%‐13.6% received nutraceuticals GAUSS‐242 Evolocumab 140 mg Q2W + placebo QD (week 12): 50.5% Evolocumab 420 mg QM+ placebo QD (week 12): 37.5%Goal defined
Evolocumab 24435 nutraceuticals 5.6%‐13.6% received nutraceuticals GAUSS‐242 Evolocumab 140 mg Q2W + placebo QD (week 12): 50.5% Evolocumab 420 mg QM+ placebo QD (week 12): 37.5%Goal defined as LDL‐C <70 mg/dL (<1.8 mmol/L) for all patients Ezetimibe
Evolocumab 42576 predicted reductions in cardiovascular events in ODYSSEY LONG TERM and OSLER‐1 and ‐2Alirocumab Evolocumab StudyODYSSEY LONG TERM33OSLER‐1 and ‐241Number of patients2341 (1553 alirocumab/788 placebo)4465
Evolocumab 54445 who do not achieve their LDL‐C goal with other LLTs, or in those who are statin‐intolerant.15, 17 Evolocumab is also approved for use in combination with other LLTs in patients aged 12 years and older who have
Evolocumab 54859 dose of alirocumab can be tailored to the individual and may be up‐ or down‐titrated as needed.17 Evolocumab is administered subcutaneously at a recommended dose of 140 mg every 2 weeks or 420 mg every month:
atorvastatin 18994 I30Alirocumab 75 mg Q2W: 72.2%Placebo: 2.4%78 82.7%‐85.3% received high‐intensity statin therapy ( atorvastatin 40‐80 mg QD, rosuvastatin 20‐40 mg QD or simvastatin 80 mg QD) 56.0%‐59.5% received ezetimibe ODYSSEY
atorvastatin 19227 30Alirocumab 75 mg Q2W: 81.4%Placebo: 11.3%78 86.8%‐91.5% received high‐intensity statin therapy ( atorvastatin 40‐80 mg QD, rosuvastatin 20‐40 mg QD or simvastatin 80 mg QD) 64.6%‐67.1% received ezetimibe ODYSSEY
atorvastatin 19633 63.0% Placebo: 2%12 100% received statins: 87% received high‐intensity statin (simvastatin 80 mg QD, atorvastatin ≥40 mg QD, rosuvastatin ≥20 mg QD or any dose of statin together with ezetimibe) 62% received
atorvastatin 20098 16.0% 12 MENDEL‐238: no background therapy LAPLACE‐280: 29% received high‐intensity statin therapy ( atorvastatin >40 mg QD or rosuvastatin >20 mg QD, simvastatin 80 mg or any statin plus ezetimibe), 41% received
atorvastatin 20363 statin therapy RUTHERFORD‐240: 87% received high‐intensity statin therapy (simvastatin 80 mg QD, atorvastatin ≥40 mg QD, rosuvastatin ≥20 mg QD or any dose of statin together with ezetimibe 10 mg QD), 62%
atorvastatin 20698 riskDESCARTES36,b Evolocumab 420 mg Q4W + diet + background LLT: 83.6% Evolocumab 420 mg Q4W + diet + atorvastatin 10 mg QD: 90.1% Evolocumab 420 mg Q4W + diet + atorvastatin 80 mg QD: 80.8% Evolocumab 420 mg Q4W
atorvastatin 20759 LLT: 83.6% Evolocumab 420 mg Q4W + diet + atorvastatin 10 mg QD: 90.1% Evolocumab 420 mg Q4W + diet + atorvastatin 80 mg QD: 80.8% Evolocumab 420 mg Q4W + diet + atorvastatin 80 mg QD + ezetimibe 10 mg QD: 67.0% Overall:
atorvastatin 20820 QD: 90.1% Evolocumab 420 mg Q4W + diet + atorvastatin 80 mg QD: 80.8% Evolocumab 420 mg Q4W + diet + atorvastatin 80 mg QD + ezetimibe 10 mg QD: 67.0% Overall: 82.3%Goal defined as LDL‐C <70 mg/dL (<1.8 mmol/L)
atorvastatin 21015 <70 mg/dL (<1.8 mmol/L) for all patients Placebo Q4W+ diet + background LLT: 3.2% Placebo Q4W + diet + atorvastatin 10 mg QD: 5.3% Placebo Q4W + diet + atorvastatin 80 mg QD: 6.1% Placebo Q4W + diet + atorvastatin
atorvastatin 21065 diet + background LLT: 3.2% Placebo Q4W + diet + atorvastatin 10 mg QD: 5.3% Placebo Q4W + diet + atorvastatin 80 mg QD: 6.1% Placebo Q4W + diet + atorvastatin 80 mg QD + ezetimibe 10 mg: 11.1% Overall: 6.4% 52NoneModerate‐to‐very
atorvastatin 21115 atorvastatin 10 mg QD: 5.3% Placebo Q4W + diet + atorvastatin 80 mg QD: 6.1% Placebo Q4W + diet + atorvastatin 80 mg QD + ezetimibe 10 mg: 11.1% Overall: 6.4% 52NoneModerate‐to‐very high CV riskODYSSEY MONO34,cAlirocumab
atorvastatin 21559 75 mg Q2W + statin: 82.5% Placebo: 9.4% Placebo + statin: 22.2% 24 No statin group: 0–1.4% received atorvastatin , rosuvastatin or simvastatin; 32.4%‐45.2% received other LLT Statin group: 99.4%‐100% received atorvastatin,
atorvastatin 21671 atorvastatin, rosuvastatin or simvastatin; 32.4%‐45.2% received other LLT Statin group: 99.4%‐100% received atorvastatin , rosuvastatin or simvastatin 32.4%‐45.2% received other LLT ODYSSEY CHOICE II81,d Alirocumab 150 mg
atorvastatin 22077 I31,eAlirocumab 75 mg Q2W: 75.0%Placebo: 9%24 99.5–100% received statins (high dose: 61.7%‐64.5%; atorvastatin 40‐80 mg QD or rosuvastatin 20‐40 mg QD or simvastatin 80 mg QD) 7.2%‐10.3% received ezetimibe 38.3%‐49.5%
atorvastatin 22391 10 mg QD: 45.6%24 99.8%‐100% received statins 66.4%‐66.8% received high‐intensity statin therapy ( atorvastatin 40‐80 mg QD or rosuvastatin 20‐40 mg QD) ODYSSEY LONG TERM 33,f,g Alirocumab 150 mg Q2W (high
atorvastatin 22777 tolerated daily statin therapy ≥99.9% received statins 46.7%‐46.8% received high‐intensity therapy ( atorvastatin 40‐80 mg QD, rosuvastatin 20‐40 mg QD or simvastatin 80 mg QD) 13.9%‐15.0% received ezetimibe 27.9%‐28.1%
atorvastatin 22966 QD) 13.9%‐15.0% received ezetimibe 27.9%‐28.1% received other LLT YUKAWA‐237,h Evolocumab 140 mg Q2W + atorvastatin 5 mg QD: 98.0%‐100% Evolocumab 420 QM + atorvastatin 5 mg QD: 96.0%‐100% Evolocumab 140 Q2W +
atorvastatin 23022 LLT YUKAWA‐237,h Evolocumab 140 mg Q2W + atorvastatin 5 mg QD: 98.0%‐100% Evolocumab 420 QM + atorvastatin 5 mg QD: 96.0%‐100% Evolocumab 140 Q2W + atorvastatin 20 mg QD: 96.0%‐100% Evolocumab 420 mg
atorvastatin 23079 5 mg QD: 98.0%‐100% Evolocumab 420 QM + atorvastatin 5 mg QD: 96.0%‐100% Evolocumab 140 Q2W + atorvastatin 20 mg QD: 96.0%‐100% Evolocumab 420 mg QM + atorvastatin 20 mg QD: 98.0%‐100%Goal defined as
atorvastatin 23140 QD: 96.0%‐100% Evolocumab 140 Q2W + atorvastatin 20 mg QD: 96.0%‐100% Evolocumab 420 mg QM + atorvastatin 20 mg QD: 98.0%‐100%Goal defined as LDL‐C <70 mg/dL (<1.8 mmol/L) for all patients Placebo Q2W
atorvastatin 23257 20 mg QD: 98.0%‐100%Goal defined as LDL‐C <70 mg/dL (<1.8 mmol/L) for all patients Placebo Q2W + atorvastatin 5 mg QD: 0.0%‐29.0% Placebo QM + atorvastatin 5 mg QD: 4.0%‐42.0% Placebo Q2W + atorvastatin 20 mg
atorvastatin 23306 <70 mg/dL (<1.8 mmol/L) for all patients Placebo Q2W + atorvastatin 5 mg QD: 0.0%‐29.0% Placebo QM + atorvastatin 5 mg QD: 4.0%‐42.0% Placebo Q2W + atorvastatin 20 mg QD: 20.0%‐59.0% Placebo QM + atorvastatin
atorvastatin 23356 atorvastatin 5 mg QD: 0.0%‐29.0% Placebo QM + atorvastatin 5 mg QD: 4.0%‐42.0% Placebo Q2W + atorvastatin 20 mg QD: 20.0%‐59.0% Placebo QM + atorvastatin 20 mg QD: 20.0%‐88.0% 12100% received statins
atorvastatin 23407 atorvastatin 5 mg QD: 4.0%‐42.0% Placebo Q2W + atorvastatin 20 mg QD: 20.0%‐59.0% Placebo QM + atorvastatin 20 mg QD: 20.0%‐88.0% 12100% received statins (atorvastatin 5 mg or 20 mg QD)High‐to‐very high
atorvastatin 23470 20 mg QD: 20.0%‐59.0% Placebo QM + atorvastatin 20 mg QD: 20.0%‐88.0% 12100% received statins ( atorvastatin 5 mg or 20 mg QD)High‐to‐very high CV riskODYSSEY OPTIONS I 27,iAlirocumab 75 mg Q2W + atorvastatin
atorvastatin 23576 (atorvastatin 5 mg or 20 mg QD)High‐to‐very high CV riskODYSSEY OPTIONS I 27,iAlirocumab 75 mg Q2W + atorvastatin 20/40 mg QD: 84.6%‐87.2% Ezetimibe 10 mg QD + atorvastatin 20/40 mg QD: 65.1%‐68.4% Rosuvastatin
atorvastatin 23639 OPTIONS I 27,iAlirocumab 75 mg Q2W + atorvastatin 20/40 mg QD: 84.6%‐87.2% Ezetimibe 10 mg QD + atorvastatin 20/40 mg QD: 65.1%‐68.4% Rosuvastatin 40 mg QD: 62.2% Atorvastatin 40/80 mg QD: 18.5%‐34.5% 24100%
atorvastatin 23776 65.1%‐68.4% Rosuvastatin 40 mg QD: 62.2% Atorvastatin 40/80 mg QD: 18.5%‐34.5% 24100% received statins ( atorvastatin 20 mg or 40 mg QD)ODYSSEY OPTIONS II29,iAlirocumab 75 mg Q2W + rosuvastatin 10/20 mg QD: 66.7%‐84.9% Ezetimibe
atorvastatin 24754 (18% low dose statin) 4%‐12% received rosuvastatin 0%‐6% received simvastatin 1%‐4% received atorvastatin 3–7% received other statins 18% received a low‐dose statin Only studies that reported LDL‐C goal
atorvastatin 31306 observed in 2.4% of patients receiving alirocumab and in 1.6% and 4.8% of patients receiving ezetimibe and atorvastatin , respectively.32 In GAUSS‐2, 2.0% of statin‐intolerant patients receiving evolocumab 420 mg every
ezetimibe 1959 reductions in LDL‐C levels were achieved with anti‐PCSK9 antibodies. When combined with statins (± ezetimibe ), high rates of LDL‐C goal achievement were observed (41%‐87% with alirocumab and 63%‐100% with
ezetimibe 5880 a first‐line therapeutic intervention, and as a second line, the cholesterol absorption inhibitor ezetimibe and bile sequestrants can be added to statins.3, 7 However, these therapies may not be sufficient in
ezetimibe 10226 from the IMPROVE‐IT trial21 also showed that the LDL‐C reduction associated with the addition of ezetimibe to statins followed the same correlation. In both treated and untreated non‐elderly individuals, the
ezetimibe 11926 respectively.18 In most studies, anti‐PCSK9 antibodies were used in combination with other LLTs (statins and/or ezetimibe ). LDL‐C reductions of 45.7%‐57.9% were observed with alirocumab, and 59.2%‐76.3% with evolocumab
ezetimibe 19100 (atorvastatin 40‐80 mg QD, rosuvastatin 20‐40 mg QD or simvastatin 80 mg QD) 56.0%‐59.5% received ezetimibe ODYSSEY FH II 30Alirocumab 75 mg Q2W: 81.4%Placebo: 11.3%78 86.8%‐91.5% received high‐intensity
ezetimibe 19333 (atorvastatin 40‐80 mg QD, rosuvastatin 20‐40 mg QD or simvastatin 80 mg QD) 64.6%‐67.1% received ezetimibe ODYSSEY HIGH FH54,aAlirocumab 150 mg Q2W: 41.0%Placebo: 5.7%24100% received maximally tolerated statin
ezetimibe 19722 80 mg QD, atorvastatin ≥40 mg QD, rosuvastatin ≥20 mg QD or any dose of statin together with ezetimibe ) 62% received ezetimibe Type 2 diabetes mellitusPooled meta‐analysis of four studies45, 79 Evolocumab
ezetimibe 19746 ≥40 mg QD, rosuvastatin ≥20 mg QD or any dose of statin together with ezetimibe) 62% received ezetimibe Type 2 diabetes mellitusPooled meta‐analysis of four studies45, 79 Evolocumab 140 mg Q2W: 88.0% Evolocumab
ezetimibe 20188 therapy (atorvastatin >40 mg QD or rosuvastatin >20 mg QD, simvastatin 80 mg or any statin plus ezetimibe ), 41% received non‐intensive statin therapy, 30% received no statin therapy RUTHERFORD‐240: 87%
ezetimibe 20452 80 mg QD, atorvastatin ≥40 mg QD, rosuvastatin ≥20 mg QD or any dose of statin together with ezetimibe 10 mg QD), 62% received ezetimibe 10 mg QD GAUSS‐242: 33% received LLT, 18% received low‐dose
ezetimibe 20487 QD, rosuvastatin ≥20 mg QD or any dose of statin together with ezetimibe 10 mg QD), 62% received ezetimibe 10 mg QD GAUSS‐242: 33% received LLT, 18% received low‐dose statin therapy Low‐to‐high CV riskDESCARTES36,b Evolocumab
ezetimibe 20845 Q4W + diet + atorvastatin 80 mg QD: 80.8% Evolocumab 420 mg Q4W + diet + atorvastatin 80 mg QD + ezetimibe 10 mg QD: 67.0% Overall: 82.3%Goal defined as LDL‐C <70 mg/dL (<1.8 mmol/L) for all patients Placebo
ezetimibe 21140 5.3% Placebo Q4W + diet + atorvastatin 80 mg QD: 6.1% Placebo Q4W + diet + atorvastatin 80 mg QD + ezetimibe 10 mg: 11.1% Overall: 6.4% 52NoneModerate‐to‐very high CV riskODYSSEY MONO34,cAlirocumab 75 mg
ezetimibe 21904 63.9% Alirocumab 75 mg Q2W: 70.3% Placebo Q2W: 1.8%24 30.2%‐34.5% received diet alone 59.3%‐60.3% received ezetimibe 5.2%‐10.3% received fenofibrate High CV riskODYSSEY COMBO I31,eAlirocumab 75 mg Q2W: 75.0%Placebo:
ezetimibe 22184 atorvastatin 40‐80 mg QD or rosuvastatin 20‐40 mg QD or simvastatin 80 mg QD) 7.2%‐10.3% received ezetimibe 38.3%‐49.5% received other LLT ODYSSEY COMBO II 28,fAlirocumab 75 mg Q2W: 77.0%Ezetimibe 10 mg QD:
ezetimibe 22883 (atorvastatin 40‐80 mg QD, rosuvastatin 20‐40 mg QD or simvastatin 80 mg QD) 13.9%‐15.0% received ezetimibe 27.9%‐28.1% received other LLT YUKAWA‐237,h Evolocumab 140 mg Q2W + atorvastatin 5 mg QD: 98.0%‐100% Evolocumab
ezetimibe 29244 the safety profile of statins in general, the risk of AEs is impacted minimally by the addition of ezetimibe .57Musculoskeletal events such as back pain or arthralgia are also among the most common AEs reported
ezetimibe 31292 (>3×ULN) were observed in 2.4% of patients receiving alirocumab and in 1.6% and 4.8% of patients receiving ezetimibe and atorvastatin, respectively.32 In GAUSS‐2, 2.0% of statin‐intolerant patients receiving evolocumab
ezetimibe 31500 evolocumab 420 mg every month had elevated creatinine kinase levels (>5×ULN) compared with 0% in the ezetimibe group. Elevated levels of creatinine kinase were not observed in the evolocumab 140 mg every 2 weeks
ezetimibe 31655 were not observed in the evolocumab 140 mg every 2 weeks group, but were seen in the corresponding ezetimibe group (6%).42There are case reports documenting mild and reversible impaired cognitive function in patients
ezetimibe 33992 with statins include elevated liver enzymes, which may occur more frequently in patients receiving ezetimibe ‐statin combination therapy than with statin monotherapy.57 Differences in levels of liver enzymes
ezetimibe 38163 drug: agents that increase the number of LDL receptors, such as statins, anti‐PCSK9 antibodies and ezetimibe , are likely to reduce CV risk.72 Drugs with a different mechanism of action, such as inhibitors of the
ezetimibe 39650 end‐point of this study was a composite of CV death, major coronary event and non‐fatal stroke. Adding ezetimibe to statin therapy in patients with mean LDL‐C levels within guideline recommendations (<70 mg/dL
ezetimibe 41152 predicted reduction in CVE rate of 22% for every 38.7 mg/dL (1 mmol/L) reduction in LDL‐C in statin and ezetimibe trials, and the LDL‐C reductions reported (at 24 and 12 weeks in two anti‐PCSK9 antibody trials,
ezetimibe 43815 antibody‐mediated LDL‐C lowering (assuming that the same benefit is observed as with statin and ezetimibe ) to predict 10‐year NNTs with anti‐PCSK9 antibodies to prevent one CVE for patients with varying
ezetimibe 45143 residual CVE risk and who are receiving an anti‐PCSK9 antibody as add‐on therapy to statin and ezetimibe . CVE, cardiovascular event; LDL‐C, low‐density lipoprotein cholesterol; NNT, number needed to treat;
ezetimibe 49658 has very high baseline LDL‐C levels (scenario A) despite receiving maximally tolerated statin plus ezetimibe and (scenario B) under ezetimibe treatment in the scenario of statin intolerance. On the basis of
ezetimibe 49691 levels (scenario A) despite receiving maximally tolerated statin plus ezetimibe and (scenario B) under ezetimibe treatment in the scenario of statin intolerance. On the basis of the overall results from ODYSSEY
ezetimibe 49993 would be anticipated in scenario A following the addition of an anti‐PCSK9 antibody to a statin plus ezetimibe . Using estimates from the CTT trial, this would translate into a 47% reduction in relative risk of major
ezetimibe 50235 Assuming a predicted 10‐year absolute risk of CV death of 20% for this patient (Figure 3), the use of ezetimibe plus maximally tolerated statin would half this risk (9%). Anti‐PCSK9 antibody as an add‐on therapy
ezetimibe 50493 terms of absolute 10‐year risk of a major CVE (fatal and non‐fatal), an anti‐PCSK9 antibody with ezetimibe and maximally tolerated statin would reduce the 10‐year absolute CVE risk from 60% to 15%. Addition
ezetimibe 50647 the 10‐year absolute CVE risk from 60% to 15%. Addition of an anti‐PCSK9 antibody to statin and ezetimibe gives a NNT of 8. We have applied the same principles to another scenario (scenario B). This patient
ezetimibe 50976 intolerant. In this case, and using data from the ODYSSEY ALTERNATIVE trial32 and the CTT meta‐analysis,5 ezetimibe slightly reduced the 10‐year absolute risk of CV death from 20% to 17%; treatment with anti‐PCSK9
ezetimibe 51331 NNT for the addition of an anti‐PCSK9 antibody to ezetemibe therapy was 4, compared with 10 with ezetimibe alone. In both scenarios, it was assumed that treatments were well tolerated and that patients were
ezetimibe 51551 to treatmentScenario AParameterBaselineEzetimibe + maximally tolerated statinAnti‐PCSK9 antibody + ezetimibe + maximally tolerated statinLDL‐C, mg/dL (mmol/L)261 (6.7)141 (3.6)41 (1.1)Predicted reduction in
ezetimibe 52206 treatmentfScenario B: Statin intoleranceParameterBaseline without statinsEzetimibe aloneAnti‐PCSK9 antibody + ezetimibe LDL‐C, mg/dL (mmol/L)191 (4.9)163 (4.2)51 (1.3)Predicted reduction in LDL‐C (% change vs previous
ezetimibe 55637 LDL‐C in a broad range of patient populations, and are suitable as an add‐on therapy to a statin or ezetimibe , or as a monotherapy for patients who are intolerant to statins. Current data suggest that they not
ezetimibe 58839 level and CVE risk is similar between drugs that specifically target the LDL receptor pathway (eg, ezetimibe and various statins). This contrasts with other drugs that modulate LDL‐C levels by other pathways
ezetimibe 59266 reductions induced by these agents would have the same proportional effect on CVE risk as statins and ezetimibe . Furthermore, preliminary data demonstrating a CVE risk benefit in anti‐PCSK9 antibody trials, albeit
fenofibrate 21936 Q2W: 1.8%24 30.2%‐34.5% received diet alone 59.3%‐60.3% received ezetimibe 5.2%‐10.3% received fenofibrate High CV riskODYSSEY COMBO I31,eAlirocumab 75 mg Q2W: 75.0%Placebo: 9%24 99.5–100% received statins (high
rosuvastatin 19023 72.2%Placebo: 2.4%78 82.7%‐85.3% received high‐intensity statin therapy (atorvastatin 40‐80 mg QD, rosuvastatin 20‐40 mg QD or simvastatin 80 mg QD) 56.0%‐59.5% received ezetimibe ODYSSEY FH II 30Alirocumab
rosuvastatin 19256 81.4%Placebo: 11.3%78 86.8%‐91.5% received high‐intensity statin therapy (atorvastatin 40‐80 mg QD, rosuvastatin 20‐40 mg QD or simvastatin 80 mg QD) 64.6%‐67.1% received ezetimibe ODYSSEY HIGH FH54,aAlirocumab
rosuvastatin 19660 received statins: 87% received high‐intensity statin (simvastatin 80 mg QD, atorvastatin ≥40 mg QD, rosuvastatin ≥20 mg QD or any dose of statin together with ezetimibe) 62% received ezetimibe Type 2 diabetes mellitusPooled
rosuvastatin 20125 background therapy LAPLACE‐280: 29% received high‐intensity statin therapy (atorvastatin >40 mg QD or rosuvastatin >20 mg QD, simvastatin 80 mg or any statin plus ezetimibe), 41% received non‐intensive statin therapy,
rosuvastatin 20390 therapy RUTHERFORD‐240: 87% received high‐intensity statin therapy (simvastatin 80 mg QD, atorvastatin ≥40 mg QD, rosuvastatin ≥20 mg QD or any dose of statin together with ezetimibe 10 mg QD), 62% received ezetimibe 10 mg
rosuvastatin 21573 statin: 82.5% Placebo: 9.4% Placebo + statin: 22.2% 24 No statin group: 0–1.4% received atorvastatin, rosuvastatin or simvastatin; 32.4%‐45.2% received other LLT Statin group: 99.4%‐100% received atorvastatin, rosuvastatin
rosuvastatin 21685 or simvastatin; 32.4%‐45.2% received other LLT Statin group: 99.4%‐100% received atorvastatin, rosuvastatin or simvastatin 32.4%‐45.2% received other LLT ODYSSEY CHOICE II81,d Alirocumab 150 mg Q4W: 63.9% Alirocumab
rosuvastatin 22108 75.0%Placebo: 9%24 99.5–100% received statins (high dose: 61.7%‐64.5%; atorvastatin 40‐80 mg QD or rosuvastatin 20‐40 mg QD or simvastatin 80 mg QD) 7.2%‐10.3% received ezetimibe 38.3%‐49.5% received other
rosuvastatin 22422 received statins 66.4%‐66.8% received high‐intensity statin therapy (atorvastatin 40‐80 mg QD or rosuvastatin 20‐40 mg QD) ODYSSEY LONG TERM 33,f,g Alirocumab 150 mg Q2W (high or very high risk): 80.7% Regardless
rosuvastatin 22806 therapy ≥99.9% received statins 46.7%‐46.8% received high‐intensity therapy (atorvastatin 40‐80 mg QD, rosuvastatin 20‐40 mg QD or simvastatin 80 mg QD) 13.9%‐15.0% received ezetimibe 27.9%‐28.1% received other
rosuvastatin 23855 18.5%‐34.5% 24100% received statins (atorvastatin 20 mg or 40 mg QD)ODYSSEY OPTIONS II29,iAlirocumab 75 mg Q2W + rosuvastatin 10/20 mg QD: 66.7%‐84.9% Ezetimibe 10 mg QD + rosuvastatin 10/20 mg QD: 43.1%‐57.2% Rosuvastatin
rosuvastatin 23918 OPTIONS II29,iAlirocumab 75 mg Q2W + rosuvastatin 10/20 mg QD: 66.7%‐84.9% Ezetimibe 10 mg QD + rosuvastatin 10/20 mg QD: 43.1%‐57.2% Rosuvastatin 20/40 mg QD: 29.9%‐45.0% 24100% received statins (rosuvastatin
rosuvastatin 24025 rosuvastatin 10/20 mg QD: 43.1%‐57.2% Rosuvastatin 20/40 mg QD: 29.9%‐45.0% 24100% received statins ( rosuvastatin 10 mg or 20 mg QD)Statin intolerantODYSSEY ALTERNATIVE 32Alirocumab 75 mg Q2W (up titrated to 150
rosuvastatin 24695 2.0% Ezetimibe 10 mg QD + placebo QM: 0.0% 12 33% received any LLT (18% low dose statin) 4%‐12% received rosuvastatin 0%‐6% received simvastatin 1%‐4% received atorvastatin 3–7% received other statins 18% received
simvastatin 10538 20‐year follow‐up of the West of Scotland Coronary Prevention Study (WOSCOP)22 and in the Scandinavian simvastatin survival study (4S; up to 8 years follow‐up).23 It is therefore currently accepted to use the same
simvastatin 19054 received high‐intensity statin therapy (atorvastatin 40‐80 mg QD, rosuvastatin 20‐40 mg QD or simvastatin 80 mg QD) 56.0%‐59.5% received ezetimibe ODYSSEY FH II 30Alirocumab 75 mg Q2W: 81.4%Placebo: 11.3%78 86.8%‐91.5%
simvastatin 19287 received high‐intensity statin therapy (atorvastatin 40‐80 mg QD, rosuvastatin 20‐40 mg QD or simvastatin 80 mg QD) 64.6%‐67.1% received ezetimibe ODYSSEY HIGH FH54,aAlirocumab 150 mg Q2W: 41.0%Placebo:
simvastatin 19610 68.0% Evolocumab 420 mg QM: 63.0% Placebo: 2%12 100% received statins: 87% received high‐intensity statin ( simvastatin 80 mg QD, atorvastatin ≥40 mg QD, rosuvastatin ≥20 mg QD or any dose of statin together with
simvastatin 20150 therapy LAPLACE‐280: 29% received high‐intensity statin therapy (atorvastatin >40 mg QD or rosuvastatin >20 mg QD, simvastatin 80 mg or any statin plus ezetimibe), 41% received non‐intensive statin therapy, 30% received no statin
simvastatin 20340 therapy, 30% received no statin therapy RUTHERFORD‐240: 87% received high‐intensity statin therapy ( simvastatin 80 mg QD, atorvastatin ≥40 mg QD, rosuvastatin ≥20 mg QD or any dose of statin together with
simvastatin 21589 82.5% Placebo: 9.4% Placebo + statin: 22.2% 24 No statin group: 0–1.4% received atorvastatin, rosuvastatin or simvastatin ; 32.4%‐45.2% received other LLT Statin group: 99.4%‐100% received atorvastatin, rosuvastatin or
simvastatin 21701 32.4%‐45.2% received other LLT Statin group: 99.4%‐100% received atorvastatin, rosuvastatin or simvastatin 32.4%‐45.2% received other LLT ODYSSEY CHOICE II81,d Alirocumab 150 mg Q4W: 63.9% Alirocumab 75 mg
simvastatin 22139 received statins (high dose: 61.7%‐64.5%; atorvastatin 40‐80 mg QD or rosuvastatin 20‐40 mg QD or simvastatin 80 mg QD) 7.2%‐10.3% received ezetimibe 38.3%‐49.5% received other LLT ODYSSEY COMBO II 28,fAlirocumab
simvastatin 22837 statins 46.7%‐46.8% received high‐intensity therapy (atorvastatin 40‐80 mg QD, rosuvastatin 20‐40 mg QD or simvastatin 80 mg QD) 13.9%‐15.0% received ezetimibe 27.9%‐28.1% received other LLT YUKAWA‐237,h Evolocumab
simvastatin 24725 0.0% 12 33% received any LLT (18% low dose statin) 4%‐12% received rosuvastatin 0%‐6% received simvastatin 1%‐4% received atorvastatin 3–7% received other statins 18% received a low‐dose statin Only studies
Select Disease Character Offset Disease Term Instance
diabetes mellitus 12802 HeFH.39, 43 Anti‐PCSK9 antibodies are also effective in LDL‐C lowering in patients with type 2 diabetes mellitus : pooled analyses of clinical trials of alirocumab or evolocumab in these patients revealed mean LDL‐C
diabetes mellitus 17352 were achieved by a large proportion of patients, regardless of the presence of comorbidities, type 2 diabetes mellitus , HeFH and CVD; and irrespective of baseline characteristics such as age, gender and use (and dose) of
diabetes mellitus 18021 their LDL‐C goals were not reported. A meta‐analysis of patient data from individuals with type 2 diabetes mellitus receiving evolocumab found that goal achievement was 87.0%‐88.0%.45 Goal achievement was not reported
diabetes mellitus 18219 achievement was not reported for similar alirocumab studies. The high proportion of patients with type 2 diabetes mellitus achieving their LDL‐C goals may relate to the fact that baseline LDL‐C levels in these patients
diabetes mellitus 18384 fact that baseline LDL‐C levels in these patients is slightly lower than in those without type 2 diabetes mellitus .Table 1LDL‐C goal achievement (according to the 2011 EAS/ESC guidelines53) with alirocumab and evolocumab,
diabetes mellitus 19763 rosuvastatin ≥20 mg QD or any dose of statin together with ezetimibe) 62% received ezetimibe Type 2 diabetes mellitus Pooled meta‐analysis of four studies45, 79 Evolocumab 140 mg Q2W: 88.0% Evolocumab 420 mg Q4W: 87.0% Ezetimibe
diabetes mellitus 25650 following—10‐year fatal CVD risk SCORE ≥5%; moderate chronic kidney disease; type 1 or type 2 diabetes mellitus without target organ damage; or FH. Very high CV risk: presence of one or more of the following—history
diabetes mellitus 26065 artery stent procedure; renal artery stenosis or renal artery stent procedure; or type 1 or type 2 diabetes mellitus with target organ damage. dCV risk definition not reported. eHigh CV risk: LDL‐C ≥70 mg/dL (≥1.8 mmol/L)
diabetes mellitus 26289 (≥1.8 mmol/L) and established CVD or LDL‐C ≥100 mg/dL (≥2.6 mmol/L) with CHD risk equivalents (eg, diabetes mellitus with other risk factors or chronic kidney disease) and LDL‐C ≥70 mg/dL (≥1.8 mmol/L). fHigh
diabetes mellitus 26586 CHD risk equivalent (ischaemic stroke, peripheral artery disease, moderate chronic kidney disease, or diabetes mellitus plus ≥2 additional risk factors). g17.7% of patients had heterozygous HF. hHigh CV was determined
diabetes mellitus 26974 <70 mg/dL (<1.8 mmol/L) was also assessed. iVery high CV risk: a history of CVD, including CHD, or type 2 diabetes mellitus with target organ damage and LDL‐C ≥70 mg/dL (≥1.8 mmol/L). High CV risk: no history of CVD
diabetes mellitus 27218 factors as follows—10‐year fatal CVD risk SCORE ≥5%; moderate chronic kidney disease; type 2 diabetes mellitus with no target organ damage; and LDL‐C ≥100 mg/dL (≥2.6 mmol/L). CHD, coronary heart disease;
diabetes mellitus 35619 in this population are expected. For alirocumab, a pooled analysis of data from patients with type 2 diabetes mellitus and chronic kidney disease enrolled in phase 3 trials showed no difference in LDL‐C lowering or safety
diabetes mellitus 47102 those aged over 30 years with FH and other risk factors; those aged over 40 years and with type 2 diabetes mellitus and other risk factors or microalbuminuria; patients aged over 60 years without type 2 diabetes mellitus,
diabetes mellitus 47208 diabetes mellitus and other risk factors or microalbuminuria; patients aged over 60 years without type 2 diabetes mellitus , but with multiple other risk factors and a SCORE (ie, 10‐year risk of fatal CVD) of 10% or higher.
diabetes mellitus 48132 conditions: FH; previous myocardial infarction, progressive coronary heart disease or atherosclerosis; type 2 diabetes mellitus ; moderate‐to‐severe chronic kidney disease (glomerular filtration rate <60 mL/min/1.73 m2); or
diabetes mellitus 48691 presentFamilial hypercholesterolaemiaPrevious myocardial infarction, progressive CVD or atherosclerosisType 2 diabetes mellitus Moderate‐to‐severe chronic kidney disease (GFR<60 mL/min/1.73 m2)Heart failure (New York Heart
type 2 diabetes mellitus 12795 than in HeFH.39, 43 Anti‐PCSK9 antibodies are also effective in LDL‐C lowering in patients with type 2 diabetes mellitus : pooled analyses of clinical trials of alirocumab or evolocumab in these patients revealed mean LDL‐C
type 2 diabetes mellitus 17345 goals were achieved by a large proportion of patients, regardless of the presence of comorbidities, type 2 diabetes mellitus , HeFH and CVD; and irrespective of baseline characteristics such as age, gender and use (and dose) of
type 2 diabetes mellitus 18014 achieving their LDL‐C goals were not reported. A meta‐analysis of patient data from individuals with type 2 diabetes mellitus receiving evolocumab found that goal achievement was 87.0%‐88.0%.45 Goal achievement was not reported
type 2 diabetes mellitus 18212 Goal achievement was not reported for similar alirocumab studies. The high proportion of patients with type 2 diabetes mellitus achieving their LDL‐C goals may relate to the fact that baseline LDL‐C levels in these patients
type 2 diabetes mellitus 18377 to the fact that baseline LDL‐C levels in these patients is slightly lower than in those without type 2 diabetes mellitus .Table 1LDL‐C goal achievement (according to the 2011 EAS/ESC guidelines53) with alirocumab and evolocumab,
type 2 diabetes mellitus 25643 of the following—10‐year fatal CVD risk SCORE ≥5%; moderate chronic kidney disease; type 1 or type 2 diabetes mellitus without target organ damage; or FH. Very high CV risk: presence of one or more of the following—history
type 2 diabetes mellitus 26058 carotid artery stent procedure; renal artery stenosis or renal artery stent procedure; or type 1 or type 2 diabetes mellitus with target organ damage. dCV risk definition not reported. eHigh CV risk: LDL‐C ≥70 mg/dL (≥1.8 mmol/L)
type 2 diabetes mellitus 26967 <70 mg/dL (<1.8 mmol/L) was also assessed. iVery high CV risk: a history of CVD, including CHD, or type 2 diabetes mellitus with target organ damage and LDL‐C ≥70 mg/dL (≥1.8 mmol/L). High CV risk: no history of CVD
type 2 diabetes mellitus 27211 other risk factors as follows—10‐year fatal CVD risk SCORE ≥5%; moderate chronic kidney disease; type 2 diabetes mellitus with no target organ damage; and LDL‐C ≥100 mg/dL (≥2.6 mmol/L). CHD, coronary heart disease;
type 2 diabetes mellitus 35612 evolocumab in this population are expected. For alirocumab, a pooled analysis of data from patients with type 2 diabetes mellitus and chronic kidney disease enrolled in phase 3 trials showed no difference in LDL‐C lowering or safety
type 2 diabetes mellitus 47095 prevention; those aged over 30 years with FH and other risk factors; those aged over 40 years and with type 2 diabetes mellitus and other risk factors or microalbuminuria; patients aged over 60 years without type 2 diabetes mellitus,
type 2 diabetes mellitus 47201 diabetes mellitus and other risk factors or microalbuminuria; patients aged over 60 years without type 2 diabetes mellitus , but with multiple other risk factors and a SCORE (ie, 10‐year risk of fatal CVD) of 10% or higher.
type 2 diabetes mellitus 48125 conditions: FH; previous myocardial infarction, progressive coronary heart disease or atherosclerosis; type 2 diabetes mellitus ; moderate‐to‐severe chronic kidney disease (glomerular filtration rate <60 mL/min/1.73 m2); or

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