Efficacy and safety of adding alirocumab to rosuvastatin versus adding ezetimibe or doubling the rosuvastatin dose in high cardiovascular-risk patients: The ODYSSEY OPTIONS II randomized trial

Farnier, Michel; Jones, Peter H.; Severance, Randall; Averna, Maurizio; Steinhagen‐Thiessen, Elisabeth; Colhoun, Helen M.; Du, Yunling; Hanotin, Corinne; Donahue, Stephen

doi:10.1016/j.atherosclerosis.2015.11.010

Cited by 160 publications

(118 citation statements)

References 26 publications

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“…A total of 138 study arms from 35 studies were analyzed, comprising 45 539 patients (Table S1). 5, 11, 12, 13, 14, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43 Alirocumab was used in 18 studies (28 treatment arms), and evolocumab was used in 17 studies (39 treatment arms; Figure 1); placebo was the most common control used (52 control arms), with ezetimibe used in 17 arms, and standard therapy in 2 arms. Eight studies were of an exclusively FH population, and 5 studies included only patients intolerant to statins.…”

Section: Resultsmentioning

confidence: 99%

Effect of PCSK9 Inhibitors on Clinical Outcomes in Patients With Hypercholesterolemia: A Meta‐Analysis of 35 Randomized Controlled Trials

Karatasakis

Danek

Karácsonyi

et al. 2017

JAHA

150

102

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BackgroundWe sought to examine the efficacy and safety of 2 PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors: alirocumab and evolocumab.Methods and ResultsWe performed a systematic review and meta‐analysis of randomized controlled trials comparing treatment with and without PCSK9 inhibitors; 35 randomized controlled trials comprising 45 539 patients (mean follow‐up: 85.5 weeks) were included. Mean age was 61.0±2.8 years, and mean baseline low‐density lipoprotein cholesterol was 106±22 mg/dL. Compared with no PCSK9 inhibitor therapy, treatment with a PCSK9 inhibitor was associated with a lower rate of myocardial infarction (2.3% versus 3.6%; odds ratio [OR]: 0.72 [95% confidence interval (CI), 0.64–0.81]; P<0.001), stroke (1.0% versus 1.4%; OR: 0.80 [95% CI, 0.67–0.96]; P=0.02), and coronary revascularization (4.2% versus 5.8%; OR: 0.78 [95% CI, 0.71–0.86]; P<0.001). Overall, no significant change was observed in all‐cause mortality (OR: 0.71 [95% CI, 0.47–1.09]; P=0.12) or cardiovascular mortality (OR: 1.01 [95% CI, 0.85–1.19]; P=0.95). A significant association was observed between higher baseline low‐density lipoprotein cholesterol and benefit in all‐cause mortality (P=0.038). No significant change was observed in neurocognitive adverse events (OR: 1.12 [95% CI, 0.88–1.42]; P=0.37), myalgia (OR: 0.95 [95% CI, 0.75–1.20]; P=0.65), new onset or worsening of preexisting diabetes mellitus (OR: 1.05 [95% CI, 0.95–1.17]; P=0.32), and increase in levels of creatine kinase (OR: 0.84 [95% CI, 0.70–1.01]; P=0.06) or alanine or aspartate aminotransferase (OR: 0.96 [95% CI, 0.82–1.12]; P=0.61).ConclusionsTreatment 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.

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Section: Resultsmentioning

confidence: 99%

Effect of PCSK9 Inhibitors on Clinical Outcomes in Patients With Hypercholesterolemia: A Meta‐Analysis of 35 Randomized Controlled Trials

Karatasakis

Danek

Karácsonyi

et al. 2017

JAHA

150

102

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“…This post‐hoc pooled analysis included individuals with a medical history of Type 1 or Type 2 DM and ASCVD who participated in 9 randomized, double‐blind, placebo‐ or ezetimibe‐controlled ODYSSEY Phase 3 trials with subcutaneous alirocumab administered every 2 weeks (Q2W), with trial durations of 24‐104 weeks (LONG TERM [NCT01507831],26 FH I [NCT01623115],23 FH II [NCT01709500],23 HIGH FH [NCT01617655],22 COMBO I [NCT01644175],24 COMBO II [NCT01644188],20 OPTIONS I [NCT01730040],19 OPTIONS II [NCT01730053]21 and ALTERNATIVE [NCT01709513]) 25. Individual trial results have been published previously.…”

Section: Methodsmentioning

confidence: 99%

“…Alirocumab is a PCSK9 inhibitor that signficantly reduced LDL‐C and other atherogenic lipid parameters in participants with hypercholesterolaemia in Phase 3 ODYSSEY trials,19, 20, 21, 22, 23, 24, 25, 26 including dedicated trials involving individuals with DM who were receiving insulin therapy27 or with mixed dyslipidaemia,28 with a safety profile comparable to controls. Alirocumab has also been demonstrated to reduce major adverse cardiovascular events vs placebo in patients with recent acute coronary syndrome in the ODYSSEY OUTCOMES trial 29.…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of alirocumab among individuals with diabetes mellitus and atherosclerotic cardiovascular disease in the ODYSSEY phase 3 trials

Ganda

Plutzky

Sanganalmath

et al. 2018

Diabetes Obesity Metabolism

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AimsIndividuals with both diabetes mellitus (DM) and atherosclerotic cardiovascular disease (ASCVD) are at very high risk of cardiovascular events. This post‐hoc analysis evaluated efficacy and safety of the PCSK9 inhibitor alirocumab among 984 individuals with DM and ASCVD pooled from 9 ODYSSEY Phase 3 trials.Materials and methodsChanges in low‐density lipoprotein cholesterol (LDL‐C) and other lipids from baseline to Week 24 were analysed (intention‐to‐treat) in four pools by alirocumab dosage (150 mg every 2 weeks [150] or 75 mg with possible increase to 150 mg every 2 weeks [75/150]), control (placebo/ezetimibe) and background statin usage (yes/no).ResultsAt Week 24, LDL‐C changes from baseline in pools with background statins were −61.5% with alirocumab 150 (vs −1.0% with placebo), −46.4% with alirocumab 75/150 (vs +6.3% with placebo) and −48.7% with alirocumab 75/150 (vs −20.6% with ezetimibe), and −54.9% with alirocumab 75/150 (vs +4.0% with ezetimibe) without background statins. A greater proportion of alirocumab recipients achieved LDL‐C < 70 and < 55 mg/dL at Week 24 vs controls. Alirocumab also resulted in significant reductions in non‐high‐density lipoprotein cholesterol, apolipoprotein B and lipoprotein(a) vs controls. Alirocumab did not appear to affect glycaemia over 78‐104 weeks. Overall safety was similar between treatment groups, with a higher injection‐site reaction frequency (mostly mild) with alirocumab.ConclusionAlirocumab significantly reduced LDL‐C and other atherogenic lipid parameters, and was generally well tolerated in individuals with DM and ASCVD.

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“…Details of the design of each of these studies have been reported previously (Figure 1). 13, 14, 15, 16, 17, 18, 19, 20, 21 The data, analytic methods, and study materials for this secondary analysis will not be made available to other researchers for purposes of reproducing the results or replicating the procedure.…”

Section: Methodsmentioning

confidence: 99%

Lower On‐Treatment Low‐Density Lipoprotein Cholesterol and Major Adverse Cardiovascular Events in Women and Men: Pooled Analysis of 10 ODYSSEY Phase 3 Alirocumab Trials

Vallejo‐Vaz

Ginsberg

Davidson

et al. 2018

JAHA

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BackgroundIn statin trials, men and women derived similar relative risk reductions in cardiovascular events per 39 mg/dL low‐density lipoprotein cholesterol (LDL‐C) reduction. We explored whether lower LDL‐C levels and greater LDL‐C percentage reductions than those achieved with statins are associated with reduced major adverse cardiovascular event (MACE) rates in women as well as men.Methods and ResultsData pooled from 10 phase 3 ODYSSEY randomized trials (n=4983) comparing alirocumab with control (placebo/ezetimibe) were assessed for association between 39 mg/dL lower on‐treatment LDL‐C and percentage LDL‐C change from baseline, and MACE risk by sex, using multivariable Cox regression. Mean baseline LDL‐C was 135 mg/dL (women) and 121 mg/dL (men). Average on‐treatment LDL‐C levels with alirocumab, ezetimibe, and placebo were 71, 114, and 134 mg/dL, respectively, in women (n=1882) and 52, 93, and 122 mg/dL, respectively, in men (n=3090). Overall, 36.5% and 58.7% of women and men, respectively, achieved on‐treatment LDL‐C <50 mg/dL. Each 39 mg/dL lower LDL‐C was associated with a 33% and 22% lower risk of MACE in women (P=0.0209) and men (P=0.0307), respectively, with no significant between‐sex difference (P for heterogeneity=0.4597). Results were similar when analyzed per 50% LDL‐C reduction, 24% (P=0.1094) and 29% (P=0.0125) lower MACE risk in women and men, respectively (P for heterogeneity=0.7499). Alirocumab was generally well tolerated in both sexes.ConclusionsThe present analysis reinforces the notion that both sexes derive a similar cardiovascular benefit from LDL‐C lowering. Although women had slightly higher on‐treatment LDL‐C than men, both sexes showed a similar lower MACE risk with lower LDL‐C.

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Efficacy and safety of adding alirocumab to rosuvastatin versus adding ezetimibe or doubling the rosuvastatin dose in high cardiovascular-risk patients: The ODYSSEY OPTIONS II randomized trial

Abstract: The addition of alirocumab to rosuvastatin provided incremental LDL-C lowering versus adding ezetimibe or doubling the rosuvastatin dose.

Cited by 160 publications

References 26 publications

Effect of PCSK9 Inhibitors on Clinical Outcomes in Patients With Hypercholesterolemia: A Meta‐Analysis of 35 Randomized Controlled Trials

Effect of PCSK9 Inhibitors on Clinical Outcomes in Patients With Hypercholesterolemia: A Meta‐Analysis of 35 Randomized Controlled Trials

Efficacy and safety of alirocumab among individuals with diabetes mellitus and atherosclerotic cardiovascular disease in the ODYSSEY phase 3 trials

Lower On‐Treatment Low‐Density Lipoprotein Cholesterol and Major Adverse Cardiovascular Events in Women and Men: Pooled Analysis of 10 ODYSSEY Phase 3 Alirocumab Trials

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