Format

Send to

Choose Destination
Circulation. 2018 Dec 18;138(25):2884-2894. doi: 10.1161/CIRCULATIONAHA.118.034516.

Effects of Liraglutide on Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus With or Without History of Myocardial Infarction or Stroke.

Author information

1
Division of Cardiac Surgery (S.V.), Canada.
2
Imperial College London, United Kingdom (N.R.P.).
3
Brigham and Women's Hospital Heart and Vascular Center and Harvard Medical School, Boston, MA (D.L.B.).
4
Institute of Life Science, Swansea University, United Kingdom (S.C.B.).
5
University of North Carolina School of Medicine, Chapel Hill (J.B.B.).
6
St Michael's Hospital and University of Toronto (L.A.L.), Canada.
7
Diabetes Center Bochum-Hattingen, St Josef-Hospital, Ruhr-University Bochum, Germany (M.A.N.).
8
Florida Hospital Translational Research Institute for Metabolism and Diabetes, Orlando (R.E.P.).
9
Lunenfeld Tanebaum Research Institute, Mount Sinai Hospital, University of Toronto, Canada (B.Z.).
10
Novo Nordisk A/S, Søborg, Denmark (D.D.Ø., T.M.F., S.R.).
11
Hospital Corporation of America (HCA) Midwest Health Heart & Vascular Institute, Kansas City, MO (S.P.M.).

Abstract

BACKGROUND:

The glucagon-like peptide-1 analog liraglutide reduced cardiovascular events and mortality in patients with type 2 diabetes mellitus in the LEADER trial (Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes). In a post hoc analysis, we evaluated the efficacy of liraglutide in those with and without a history of myocardial infarction (MI) and/or stroke.

METHODS:

LEADER was a randomized trial of liraglutide (1.8 mg or maximum tolerated dose) versus placebo in 9340 patients with type 2 diabetes mellitus and high cardiovascular risk, with a median follow-up of 3.8 years. The primary outcome was a composite of cardiovascular death, nonfatal MI, or nonfatal stroke (major adverse cardiovascular events). Risk groups in this post hoc analysis were defined by history of MI/stroke, established atherosclerotic cardiovascular disease without MI/stroke, or cardiovascular risk factors alone.

RESULTS:

Of the 9340 patients, 3692 (39.5%) had a history of MI/stroke, 3083 (33.0%) had established atherosclerotic cardiovascular disease without MI/stroke, and 2565 (27.5%) had risk factors alone. Major adverse cardiovascular events occurred in 18.8% of patients with a history of MI/stroke (incidence rate, 5.0 per 100 patient-years), 11.6% of patients with established atherosclerotic cardiovascular disease without MI/stroke (incidence rate, 3.0 per 100 patient-years), and 9.8% of patients with cardiovascular risk factors alone (incidence rate, 2.6 per 100 patient-years). Liraglutide reduced major adverse cardiovascular events in patients with a history of MI/stroke (322 of 1865 [17.3%] versus 372 of 1827 patients [20.4%]; hazard ratio, 0.85; 95% CI, 0.73-0.99) and in those with established atherosclerotic cardiovascular disease without MI/stroke (158 of 1538 [10.3%] versus 199 of 1545 patients [12.9%]; hazard ratio, 0.76; 95% CI, 0.62-0.94) compared with placebo. In patients with risk factors alone, the hazard ratio for liraglutide versus placebo was 1.08 (95% CI, 0.84-1.38, Pinteraction=0.11). Similar results were seen for secondary outcomes across risk groups.

CONCLUSIONS:

In this post hoc analysis of patients with type 2 diabetes mellitus and high cardiovascular risk, liraglutide reduced cardiovascular outcomes both in patients with a history of MI/stroke and in those with established atherosclerotic cardiovascular disease without MI/stroke. The cardiovascular effect appeared neutral in patients with cardiovascular risk factors alone.

CLINICAL TRIAL REGISTRATION:

URL: https://www.clinicaltrials.gov . Unique identifier: NCT01179048.

KEYWORDS:

cardiovascular system; diabetes mellitus; glucagon-like peptide-1; liraglutide; randomized controlled trial as topic; type 2

Supplemental Content

Full text links

Icon for Atypon
Loading ...
Support Center