Efficacy and Safety of Alirocumab Versus Ezetimibe Over 2 Years (from ODYSSEY COMBO II)

Shahawy, Mahfouz El; Cannon, Christopher P.; Blom, Dirk; McKenney, James M.; Cariou, Bertrand; Lecorps, Guillaume; Pordy, Robert; Chaudhari, Umesh; Colhoun, Helen M.

doi:10.1016/j.amjcard.2017.06.023

Cited by 26 publications

(15 citation statements)

References 18 publications

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“…Significant decline in the concentrations of total cholesterol, non HDL-C and apolipoprotein B were also observed (p <0.0001). Additionally as per Shahawy et al 13 LDL-C levels showed significant reductions from baseline by 52% with Alirocumab whereas by 22% with the Ezetimibe group ( [4.9] % for the subjects of ITT analysis group, associated with a statistically significant LS mean (SE) difference among the groups of −39.1 (6.0) % (P < 0.0001). A sensitivity analysis was also done and resultant demonstration of Alirocumab with −50.9 [3.4] % and placebo with −1.0 [4.7] % in LDL-C (P <0.0001).…”

Section: Ldl-c Reductionmentioning

confidence: 58%

“…Some studies also showed that the difference in Triglyceride levels between Alirocumab and Ezetimibe arm was not statistically significant. 13,15 Modest HDL-C elevation was also documented attributed to Alirocumab as compared to control. Other lipid parameters are shown in Table 3.…”

Section: Ldl-c Goal Attainmentmentioning

confidence: 90%

“…16 In the study conducted by Leiter et al cardiovascular events were reported in 8.8% and 2.6% of subjects with DM and 5.4% and 6.7% of subjects without diabetes mellitus for the interventional and Ezetimibe arms respectively. 17 Leiter et al [13] (…”

Section: Safety Summarymentioning

confidence: 99%

“…Teramoto et al [16] (2016) Bays et al [17] ( Kereiakes et al [20] (2015) Roth et al [21] (2012) Atorvastatin Shahawy et al [11] (2017) Leiter et al [13] (2016) Farnier et al [14] (2016)…”

Section: 1%mentioning

confidence: 99%

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Alirocumab in Combination with Statins for CVD Risk Reduction: An Evidential Review

Satyanarayan¹,

Siva²,

Tsundue³

et al. 2018

SRP

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Cardiovascular disorders have been one of the mainstay causes for the estimated rise in the incidences of mortality. In earlier times, treatment approach was initiated with statin therapy even though there were high reports of adverse events and failure to attain the target lipid concentration. In 2003, Proprotein Convertase subtilisin/kexin 9 was found to be responsible for the degradation and inactivation of LDL receptors. Ever since the concept was introduced, many researches have been conducted in this field for a better control in lipid management. Alirocumab was approved by FDA in the year 2015 as a PCSK9 inhibitor indicated for heterozygous familial hypercholesterolemia. The purpose of this review is to compile the available information on the LDL-C reduction capacity of Alirocumab in combination with statins and simultaneous cardiovascular risk reduction. It also aims at providing an evidential safety data associated with Alirocumab use. Alirocumab is presently available in doses of 75 and 150mg subcutaneous injections once every two weeks. It is a monoclonal antibody directed against PCSK9 and evidential data provides an estimate of about 54% reduction in LDL-C concentrations. The application of Alirocumab as add on therapy to statins is the area of interest and the data suggests that there is a significant higher rate of LDL-C reductions in turn leading to a noteworthy cardiovascular risk reduction. However the appropriate dose of statins to incorporate a PCSK9 inhibitor requires further hypotheses. Additionally the safety profile of Alirocumab was found to be comparable with placebo or the control.

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Section: Ldl-c Reductionmentioning

confidence: 58%

Section: Ldl-c Goal Attainmentmentioning

confidence: 90%

Section: Safety Summarymentioning

confidence: 99%

“…Teramoto et al [16] (2016) Bays et al [17] ( Kereiakes et al [20] (2015) Roth et al [21] (2012) Atorvastatin Shahawy et al [11] (2017) Leiter et al [13] (2016) Farnier et al [14] (2016)…”

Section: 1%mentioning

confidence: 99%

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Alirocumab in Combination with Statins for CVD Risk Reduction: An Evidential Review

Satyanarayan¹,

Siva²,

Tsundue³

et al. 2018

SRP

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“…In the studies included in this analysis, patients at high risk for cardiovascular events who had elevated LDL-C despite maximally tolerated statin received alirocumab or control as follows: COMBO I (NCT01644175) evaluated alirocumab 75 mg every 2 weeks (Q2W), with possible dose increase to 150 mg Q2W, vs placebo for 52 weeks 10 ; COMBO II (NCT01644188) evaluated alirocumab 75 mg Q2W, with possible dose increase to 150 mg Q2W, vs ezetimibe for 104 weeks 7,11 ; and LONG TERM (NCT01507831) evaluated alirocumab 150 mg Q2W vs placebo for 78 weeks. 9 Throughout the trials, all patients continued to receive their maximally tolerated statin dose and other lipid-lowering therapies (LLTs), except for COMBO II, where other LLTs were not used.…”

Section: Methodsmentioning

confidence: 99%

Alirocumab efficacy and safety by race and ethnicity: Analysis from 3 ODYSSEY phase 3 trials

Ferdinand

Jacobson

Koren

et al. 2019

Journal of Clinical Lipidology

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BACKGROUND: Differences in lipid and cardiovascular risk profiles have been observed in African-American/black (AA/B), white (W), and Hispanic/Latino (H/L) individuals. Efficacy and safety of alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, may vary by race and ethnicity and has not been analyzed. OBJECTIVE: This post hoc analysis evaluated alirocumab efficacy and safety vs control in 3 pooled ODYSSEY phase 3 trials (COMBO I, COMBO II, and LONG TERM) by race (AA/B [n 5 154] vs W [n 5 1982]) and ethnicity (H/L [n 5 174] vs non-H/L [n 5 3149]). METHODS: Patients with elevated low-density lipoprotein cholesterol (LDL-C) despite maximally tolerated statin received alirocumab (75 mg up to 150 mg every 2 weeks [COMBO I & II] or 150 mg every 2 weeks [LONG TERM]) or control (placebo [COMBO I and LONG TERM] or ezetimibe [COMBO II]). RESULTS: At baseline, LDL-C levels were similar across treatment groups; median lipoprotein(a) levels were higher in AA/B (33.0-120.0 mg/dL) vs W (7.1-66.3 mg/dL) and lower in H/L (5.0-38.3 mg/dL) vs non-H/L (7.7-69.0 mg/dL). At week 24, alirocumab significantly reduced LDL-C vs control. Alirocumab also reduced lipoprotein(a) compared with control across the subgroups. Treatment-emergent adverse events were similar between alirocumab (68.9-85.0%) and control (70.6-82.4%) regardless of race and ethnicity. CONCLUSION: Alirocumab significantly reduced LDL-C and Lp(a) levels compared with control, regardless of race and ethnicity, with overall safety comparable to control across most of the racial and ethnic groups analyzed.

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PCSK9 monoclonal antibodies for the primary and secondary prevention of cardiovascular disease

Schmidt

Carter

Pearce

et al. 2020

Cochrane Database of Systematic Reviews

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BackgroundDespite the availability of effective drug therapies that reduce low-density lipoprotein (LDL)-cholesterol (LDL-C), cardiovascular disease (CVD) remains an important cause of mortality and morbidity. Therefore, additional LDL-C reduction may be warranted, especially for patients who are unresponsive to, or unable to take, existing LDL-C-reducing therapies. By inhibiting the proprotein convertase subtilisin/kexin type 9 (PCSK9) enzyme, monoclonal antibodies (PCSK9 inhibitors) may further reduce LDL-C, potentially reducing CVD risk as well. Objectives PrimaryTo quantify short-term (24 weeks), medium-term (one year), and long-term (five years) effects of PCSK9 inhibitors on lipid parameters and on the incidence of CVD. SecondaryTo quantify the safety of PCSK9 inhibitors, with specific focus on the incidence of type 2 diabetes, cognitive function, and cancer. Additionally, to determine if specific patient subgroups were more or less likely to benefit from the use of PCSK9 inhibitors. Search methodsWe identified studies by systematically searching the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and Web of Science. We also searched Clinicaltrials.gov and the International Clinical Trials Registry Platform and screened the reference lists of included studies. We identified the studies included in this review through electronic literature searches conducted up to May 2016, and added three large trials published in March 2017. Selection criteriaAll parallel-group and factorial randomised controlled trials (RCTs) with a follow-up time of at least 24 weeks were eligible. 1 PCSK9 monoclonal antibodies for the primary and secondary prevention of cardiovascular disease (Review)

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Efficacy and Safety of Alirocumab Versus Ezetimibe Over 2 Years (from ODYSSEY COMBO II)

Cited by 26 publications

References 18 publications

Alirocumab in Combination with Statins for CVD Risk Reduction: An Evidential Review

Alirocumab in Combination with Statins for CVD Risk Reduction: An Evidential Review

Alirocumab efficacy and safety by race and ethnicity: Analysis from 3 ODYSSEY phase 3 trials

PCSK9 monoclonal antibodies for the primary and secondary prevention of cardiovascular disease

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