Dataset Information

Lipid-lowering efficacy and safety of alirocumab in patients with or without diabetes: A sub-analysis of ODYSSEY COMBO II.

ABSTRACT: AIM:This sub-analysis of the ODYSSEY COMBO II study compared the effects of alirocumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, in high cardiovascular risk patients with or without diabetes mellitus (DM) receiving maximally tolerated statin therapy. METHODS:COMBO II was a 104-week, double-blind study (n?=?720) enrolling patients with documented atherosclerotic cardiovascular disease (ASCVD) and baseline LDL-C ?70?mg/dL (1.8?mmol/L), and patients without documented ASCVD at high cardiovascular risk with LDL-C ?100?mg/dL (2.6?mmol/L). Patients receiving maximally tolerated statin therapy were randomized (2:1) to alirocumab 75?mg every 2?weeks (Q2W; 1?mL subcutaneous injection) or oral ezetimibe 10?mg daily. Alirocumab dose was increased to 150?mg Q2W (also 1?mL) at Week 12 if Week 8 LDL-C was ?70?mg/dL. RESULTS:History of DM was reported in 31% (n?=?148) of patients on alirocumab and 32% (n?=?77) of patients on ezetimibe. At Week 24, alirocumab consistently reduced LDL-C from baseline in patients with (-49.1%) or without DM (-51.2%) to a significantly greater extent than ezetimibe (-18.4% and -21.8%, respectively). Occurrence of treatment-emergent adverse events was similar between groups. Efficacy results at 104?weeks were similar to those at 24?weeks. CONCLUSIONS:Over a 104-week double-blind study period, alirocumab provided consistently greater LDL-C reductions than ezetimibe, with similar LDL-C results in patients with or without DM. Safety of alirocumab was similar regardless of baseline DM status.

SUBMITTER: Leiter LA

PROVIDER: S-EPMC5485164 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Lipid-lowering efficacy and safety of alirocumab in patients with or without diabetes: A sub-analysis of ODYSSEY COMBO II.

Leiter Lawrence A LA Zamorano José Luis JL Bujas-Bobanovic Maja M Louie Michael J MJ Lecorps Guillaume G Cannon Christopher P CP Handelsman Yehuda Y

Diabetes, obesity & metabolism 20170418 7

<h4>Aim</h4>This sub-analysis of the ODYSSEY COMBO II study compared the effects of alirocumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, in high cardiovascular risk patients with or without diabetes mellitus (DM) receiving maximally tolerated statin therapy.<h4>Methods</h4>COMBO II was a 104-week, double-blind study (n = 720) enrolling patients with documented atherosclerotic cardiovascular disease (ASCVD) and baseline LDL-C ≥70 mg/dL (1.8 mmol/L), and patients without ...[more]

PMID: 28206704

Similar Datasets

Project description:Type 2 diabetes mellitus (T2DM) is often associated with mixed dyslipidaemia, where non-high-density lipoprotein cholesterol (non-HDL-C) levels may more closely align with cardiovascular risk than low-density lipoprotein cholesterol (LDL-C). We describe the design and rationale of the ODYSSEY DM-DYSLIPIDEMIA study that assesses the efficacy and safety of alirocumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, versus lipid-lowering usual care in individuals with T2DM and mixed dyslipidaemia at high cardiovascular risk with non-HDL-C inadequately controlled despite maximally tolerated statin therapy. For the first time, atherogenic cholesterol-lowering with a PCSK9 inhibitor will be assessed with non-HDL-C as the primary endpoint with usual care as the comparator.DM-DYSLIPIDEMIA is a Phase 3b/4, randomised, open-label, parallel group, multinational study that planned to enrol 420 individuals. Main inclusion criteria were T2DM and mixed dyslipidaemia (non-HDL-C ?100 mg/dl [?2.59 mmol/l], and triglycerides ?150 and <500 mg/dl [?1.70 and <5.65 mmol/l]) with documented atherosclerotic cardiovascular disease or ?1 additional cardiovascular risk factor. Participants were randomised (2:1) to alirocumab 75 mg every 2 weeks (Q2W) or lipid-lowering usual care on top of maximally tolerated statin (or no statin if intolerant). If randomised to usual care, investigators were able to add their pre-specified choice of one of the following to the patient's current statin regimen: ezetimibe, fenofibrate, omega-3 fatty acids or nicotinic acid, in accordance with local standard-of-care. Alirocumab-treated individuals with non-HDL-C ?100 mg/dl at week 8 will undergo a blinded dose increase to 150 mg Q2W at week 12. The primary efficacy endpoint is non-HDL-C change from baseline to week 24 with alirocumab versus usual care; other lipid levels (including LDL-C), glycaemia-related measures, safety and tolerability will also be assessed. Alirocumab will be compared to fenofibrate in a secondary analysis.Recruitment completed with 413 individuals randomised in 14 countries worldwide. Results of this trial are expected in the second quarter of 2017.ODYSSEY DM-DYSLIPIDEMIA will provide information on the efficacy and safety of alirocumab versus lipid-lowering usual care in individuals with T2DM and mixed dyslipidaemia at high cardiovascular risk using non-HDL-C as the primary efficacy endpoint. Trial registration NCT02642159 (registered December 24, 2015).

Project description:AimsLipoprotein(a) concentration is associated with first cardiovascular events in clinical trials. It is unknown if this relationship holds for total (first and subsequent) events. In the ODYSSEY OUTCOMES trial in patients with recent acute coronary syndrome (ACS), the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab reduced lipoprotein(a), low-density lipoprotein cholesterol (LDL-C), and cardiovascular events compared with placebo. This post hoc analysis determined whether baseline levels and alirocumab-induced changes in lipoprotein(a) and LDL-C [corrected for lipoprotein(a) cholesterol] independently predicted total cardiovascular events.Methods and resultsCardiovascular events included cardiovascular death, non-fatal myocardial infarction, stroke, hospitalization for unstable angina or heart failure, ischaemia-driven coronary revascularization, peripheral artery disease events, and venous thromboembolism. Proportional hazards models estimated relationships between baseline lipoprotein(a) and total cardiovascular events in the placebo group, effects of alirocumab treatment on total cardiovascular events by baseline lipoprotein(a), and relationships between lipoprotein(a) reduction with alirocumab and subsequent risk of total cardiovascular events. Baseline lipoprotein(a) predicted total cardiovascular events with placebo, while higher baseline lipoprotein(a) levels were associated with greater reduction in total cardiovascular events with alirocumab (hazard ratio Ptrend = 0.045). Alirocumab-induced reductions in lipoprotein(a) (median -5.0 [-13.6, 0] mg/dL) and corrected LDL-C (median -51.3 [-67.1, -34.0] mg/dL) independently predicted lower risk of total cardiovascular events. Each 5-mg/dL reduction in lipoprotein(a) predicted a 2.5% relative reduction in cardiovascular events.ConclusionBaseline lipoprotein(a) predicted the risk of total cardiovascular events and risk reduction by alirocumab. Lipoprotein(a) lowering contributed independently to cardiovascular event reduction, supporting the concept of lipoprotein(a) as a treatment target after ACS.

Dataset Information

Lipid-lowering efficacy and safety of alirocumab in patients with or without diabetes: A sub-analysis of ODYSSEY COMBO II.

Publications

Lipid-lowering efficacy and safety of alirocumab in patients with or without diabetes: A sub-analysis of ODYSSEY COMBO II.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets