Trial DesignRationale, design, and baseline characteristics in Evaluation of LIXisenatide in Acute Coronary Syndrome, a long-term cardiovascular end point trial of lixisenatide versus placebo
Section snippets
Glucose-lowering therapy and CV risk
Evidence-based primary and secondary CV risk reduction strategies, such as the use of statins,13, 14 angiotensin-converting enzyme inhibitors, and β-blockers,15, 16, 17 are effective in patients with T2DM. However, the role of glycemic control in CV risk reduction is less clear. A meta-analysis of clinical trials suggested that intensive glycemic control in patients with T2DM reduced the risk of nonfatal myocardial infarction (MI) but did not reduce total or CV-related mortality.18 Furthermore,
Study design and objectives
ELIXA (www.clinicaltrials.gov no. NCT01147250) is a randomized, double-blind, placebo-controlled, parallel-group, multicenter phase III event-driven trial designed to assess the effects of lixisenatide added to current T2DM therapy on CV morbidity and mortality in patients with a recent ACS. The primary outcome is the composite of CV death, nonfatal MI, nonfatal stroke, or hospitalization for unstable angina (UA). Secondary trial objectives include the examination of lixisenatide's effects on
Results
Screening and enrollment into ELIXA began June 24, 2010, and randomization was completed on August 2, 2013. There were 7,718 candidates screened and 6,068 participants randomized to either lixisenatide or placebo (online Appendix A) from 49 countries across 6 regions (online Appendix E) with the support of 782 principal investigators (online Appendix F). One additional candidate was screened and randomized but excluded from analysis due to inadequate consent. Baseline data include data
Discussion
ELIXA will determine the effects of lixisenatide, a GLP-1RA, compared to placebo on the burden of CV disease in patients with T2DM and ACS. Although native GLP-1 and GLP-1RAs exert favorable CV effects in animal models of MI and ischemia/reperfusion injury,40, 41, 42 few data exist in humans. In small placebo-controlled studies, GLP-1RA treatment improved myocardial salvage and reduced infarct size.43, 44 A larger retrospective analysis revealed that the nonrandomized use of GLP-1RA was
Disclosures
The authors have the following disclosures:
R. Bentley-Lewis: consultant and research support—Sanofi; research support, spouse/partner—Sanofi; Amgen, Inc; and Novartis Pharmaceuticals Corporation. D. Aguilar: consultant—Bristol-Myers Squibb Company and Sanofi. M.C. Riddle: consultant—Eli Lilly and Company, AstraZeneca Pharmaceuticals LP, Sanofi, Valeritas, LLC, and Elcelyx Therapeutics, Inc; research support—AstraZeneca Pharmaceuticals LP, Eli Lilly, and Company, Sanofi, Novo Nordisk, Inc; other
Acknowledgements
We thank Jennifer Huynh, BA, and Rebecca Walmer, BA, salaried research assistants employed by Rhonda Bentley-Lewis, MD, for their assistance with literature review and manuscript formatting.
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2020, Journal of Diabetes and its ComplicationsCitation Excerpt :GLP1 analogues are thought to be capable of reducing cardiovascular risk through several path- ways in addition or beyond their effect on blood glucose, such as: weight loss promotion, reduction in blood pressure, decreased myocardial and vascular inflammation, lower platelet aggregation, and others.39 The relative importance of these and other mechanisms is a subject of great interest in light of the three large, cardiovascular non-inferiority RCTs that have been conducted to date on GLP-1agonists inT2DM: ELIXA57, LEADER12 and SUSTAIN-611 using lixisenatide, liraglutide and semaglutide respectively. Lixisenatide trial on 6068 patients follow-up of 2.1 years, demonstrated non- inferiority to placebo and no significant difference between treatment groups was observed.
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Clinical registration trial: www.clinicaltrials.gov no. NCT01147250.