Effects of Liraglutide on Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus With or Without History of Myocardial Infarction or Stroke
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.
| Errataetall: |
CommentIn: J Thorac Cardiovasc Surg. 2020 Mar;159(3):978-984. - PMID 31227180 |
|---|---|
| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2018 |
|---|---|
| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:138 |
|---|---|
| Enthalten in: |
Circulation - 138(2018), 25 vom: 18. Dez., Seite 2884-2894 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Verma, Subodh [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 03.10.2019 Date Revised 07.10.2019 published: Print ClinicalTrials.gov: NCT01179048 CommentIn: J Thorac Cardiovasc Surg. 2020 Mar;159(3):978-984. - PMID 31227180 Citation Status MEDLINE |
|---|
| doi: |
10.1161/CIRCULATIONAHA.118.034516 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM291956823 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM291956823 | ||
| 003 | DE-627 | ||
| 005 | 20231225072023.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2018 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1161/CIRCULATIONAHA.118.034516 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0973.xml |
| 035 | |a (DE-627)NLM291956823 | ||
| 035 | |a (NLM)30566004 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Verma, Subodh |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Effects of Liraglutide on Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus With or Without History of Myocardial Infarction or Stroke |
| 264 | 1 | |c 2018 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 03.10.2019 | ||
| 500 | |a Date Revised 07.10.2019 | ||
| 500 | |a published: Print | ||
| 500 | |a ClinicalTrials.gov: NCT01179048 | ||
| 500 | |a CommentIn: J Thorac Cardiovasc Surg. 2020 Mar;159(3):978-984. - PMID 31227180 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01179048 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Multicenter Study | |
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a cardiovascular system | |
| 650 | 4 | |a diabetes mellitus | |
| 650 | 4 | |a glucagon-like peptide-1 | |
| 650 | 4 | |a liraglutide | |
| 650 | 4 | |a randomized controlled trial as topic | |
| 650 | 4 | |a type 2 | |
| 650 | 7 | |a Hypoglycemic Agents |2 NLM | |
| 650 | 7 | |a Liraglutide |2 NLM | |
| 650 | 7 | |a 839I73S42A |2 NLM | |
| 700 | 1 | |a Poulter, Neil R |e verfasserin |4 aut | |
| 700 | 1 | |a Bhatt, Deepak L |e verfasserin |4 aut | |
| 700 | 1 | |a Bain, Stephen C |e verfasserin |4 aut | |
| 700 | 1 | |a Buse, John B |e verfasserin |4 aut | |
| 700 | 1 | |a Leiter, Lawrence A |e verfasserin |4 aut | |
| 700 | 1 | |a Nauck, Michael A |e verfasserin |4 aut | |
| 700 | 1 | |a Pratley, Richard E |e verfasserin |4 aut | |
| 700 | 1 | |a Zinman, Bernard |e verfasserin |4 aut | |
| 700 | 1 | |a Ørsted, David D |e verfasserin |4 aut | |
| 700 | 1 | |a Monk Fries, Tea |e verfasserin |4 aut | |
| 700 | 1 | |a Rasmussen, Søren |e verfasserin |4 aut | |
| 700 | 1 | |a Marso, Steven P |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Circulation |d 1950 |g 138(2018), 25 vom: 18. Dez., Seite 2884-2894 |w (DE-627)NLM000039020 |x 1524-4539 |7 nnns |
| 773 | 1 | 8 | |g volume:138 |g year:2018 |g number:25 |g day:18 |g month:12 |g pages:2884-2894 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1161/CIRCULATIONAHA.118.034516 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 138 |j 2018 |e 25 |b 18 |c 12 |h 2884-2894 | ||