Dulaglutide and cardiovascular and heart failure outcomes in patients with and without heart failure: a post-hoc analysis from the REWIND randomized trial
Language English Country England, Great Britain Media print-electronic
Document type Randomized Controlled Trial, Journal Article, Research Support, Non-U.S. Gov't
PubMed
36073143
DOI
10.1002/ejhf.2670
Knihovny.cz E-resources
- Keywords
- Clinical trial, Dulaglutide, GLP-1, Glucagon-like peptide 1 receptor agonist, Heart failure, Heart failure hospitalization, Major adverse cardiovascular events,
- MeSH
- Diabetes Mellitus, Type 2 * complications drug therapy epidemiology MeSH
- Hypoglycemic Agents therapeutic use adverse effects MeSH
- Incretins therapeutic use MeSH
- Cardiovascular Diseases * epidemiology MeSH
- Humans MeSH
- Heart Failure * drug therapy epidemiology chemically induced MeSH
- Treatment Outcome MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Randomized Controlled Trial MeSH
- Names of Substances
- Hypoglycemic Agents MeSH
- Incretins MeSH
AIMS: People with diabetes are at high risk for cardiovascular events including heart failure (HF). We examined the effect of the glucagon-like peptide 1 agonist dulaglutide on incident HF events and other cardiovascular outcomes in those with or without prior HF in the randomized placebo-controlled Researching Cardiovascular Events with a Weekly Incretin in Diabetes (REWIND) trial. METHODS AND RESULTS: The REWIND major adverse cardiovascular event (MACE) outcome was the first occurrence of a composite endpoint of non-fatal myocardial infarction, non-fatal stroke, or death from cardiovascular causes (including unknown causes). In this post-hoc analysis, a HF event was defined as an adjudication-confirmed hospitalization or urgent evaluation for HF. Of the 9901 participants studied over a median follow-up of 5.4 years, 213/4949 (4.3%) randomly assigned to dulaglutide and 226/4952 (4.6%) participants assigned to placebo experienced a HF event (hazard ratio [HR] 0.93, 95% confidence interval [CI] 0.77-1.12; p = 0.456). In the 853 (8.6%) participants with HF at baseline, there was no change in either MACE or HF events with dulaglutide as compared to participants without HF (p = 0.44 and 0.19 for interaction, respectively). Combined cardiovascular death and HF events were marginally reduced with dulaglutide compared to placebo (HR 0.88, 95% CI 0.78-1.00; p = 0.050) but unchanged in patients with and without HF at baseline (p = 0.31). CONCLUSIONS: Dulaglutide was not associated with a reduction in HF events in patients with type 2 diabetes regardless of baseline HF status over 5.4 years of follow-up.
Baker Heart and Diabetes Institute Melbourne Victoria Australia
Department of Medicine K2 Karolinska Institute Stockholm Sweden
Division of Endocrinology and Metabolism Taipei Veterans General Hospital Taipei Taiwan
Division of Endocrinology University of Cape Town Cape Town South Africa
Eli Lilly and Co Indianapolis IN USA
Endocrinology and Nutrition Department Hospital Clínic i Universitari Barcelona Spain
International Research Center Hospital Alemão Oswaldo Cruz São Paulo Brazil
Li Ka Shing Knowledge Institute St Michael's Hospital University of Toronto Toronto Ontario Canada
Medical University of South Carolina Ralph H Johnson VA Medical Center Charleston SC USA
National Medical Research Center of Cardiology Moscow Russia
Robert Koch Medical Center Sofia Bulgaria
St John's Research Institute Bangalore India
Universidad de La Fontera Temuco Chile
University Hospital Motol Prague Czech Republic
University of Tennessee Health Science Center Memphis TN USA
See more in PubMed
Cho NH, Shaw JE, Karuranga S, Huang Y, da Rocha Fernandes JD, Ohlrogge AW, et al. IDF Diabetes Atlas: global estimates of diabetes prevalence for 2017 and projections for 2045. Diab Res Clin Pract. 2018;138:271-81.
Cavender MA, Steg PG, Smith SC, Eagle K, Ohman EM, Goto S, et al. Impact of diabetes mellitus on hospitalization for heart failure, cardiovascular events, and death. Circulation. 2015;132:923-31.
Donahoe SM, Stewart GC, McCabe CH, Mohanavelu S, Murphy SA, Cannon CP, et al. Diabetes and mortality following acute coronary syndromes. JAMA. 2007;298:765-75.
Bhatt DL, Eagle KA, Ohman EM, Hirsch AT, Goto S, Mahoney EM, et al.; REACH Registry Investigators. Comparative determinants of 4-year cardiovascular event rates in stable outpatients at risk of or with atherothrombosis. JAMA. 2010;304:1350-7.
Miao B, Hernandez AV, Alberts MJ, Mangiafico N, Roman YM, Coleman CI. Incidence and predictors of major adverse cardiovascular events in patients with established atherosclerotic disease or multiple risk factors. J Am Heart Assoc. 2020;9:e014402.
Dunlay SM, Givertz MM, Aguilar D, Allen LA, Chan M, Desai AS, et al. Type 2 diabetes mellitus and heart failure: a scientific statement from the American Heart Association and the Heart Failure Society of America. Circulation. 2019;140:e294-324.
Gerstein HC, Sattar N, Rosenstock J, Ramasundarahettige C, Pratley R, Lopes RD, et al.; AMPLITUDE-O Trial Investigators. Cardiovascular and renal outcomes with efpeglenatide in type 2 diabetes. N Engl J Med. 2021;385:896-907.
Kenny HC, Abel ED. Heart failure in type 2 diabetes mellitus. Circ Res. 2019;124:121-41.
Dauriz M, Mantovani A, Bonapace S, Verlato G, Zoppini G, Bonora E, et al. Prognostic impact of diabetes on long-term survival outcomes in patients with heart failure: a meta-analysis. Diabetes Care. 2017;40:1597-605.
Sattar N, Lee M, Kristensen SL, Branch KR, Del Prato S, Lam CSP, et al. Cardiovascular, mortality and kidney outcomes with glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes - an updated systematic review and meta-analysis of randomised trials. Lancet Diabetes Endocrinol. 2021;9:653-62.
Margulies KB, Hernandez AF, Redfield MM, Givertz MM, Oliveira GH, Cole R, et al.; NHLBI Heart Failure Clinical Research Network. Effects of liraglutide on clinical stability among patients with advanced heart failure and reduced ejection fraction: a randomized clinical trial. JAMA. 2016;316:500-8.
Hernandez AF, Green JB, Janmohamed S, D'Agostino RB, Sr., Granger CB, Jones NP, et al.; Harmony Outcomes Committees and Investigators. Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial. Lancet. 2018;392:1519-29.
Palmer SC, Tendal B, Mustafa RA, Vandvik PO, Li S, Hao Q, et al. Sodium-glucose cotransporter protein-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists for type 2 diabetes: systematic review and network meta-analysis of randomised controlled trials. BMJ. 2021;372:m4573.
Seferović PM, Coats AJS, Ponikowski P, Filippatos G, Huelsmann M, Jhund PS, et al. European Society of Cardiology/Heart Failure Association position paper on the role and safety of new glucose-lowering drugs in patients with heart failure. Eur J Heart Fail. 2020;22:196-213.
Gerstein HC, Colhoun HM, Dagenais GR, Diaz R, Lakshmanan M, Pais P, et al.; REWIND Investigators. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. Lancet. 2019;394:121-30.
Gerstein HC, Colhoun HM, Dagenais GR, Diaz R, Lakshmanan M, Pais P, et al.; REWIND Trial Investigators. Design and baseline characteristics of participants in the Researching cardiovascular Events with a Weekly INcretin in Diabetes (REWIND) trial on the cardiovascular effects of dulaglutide. Diabetes Obes Metab. 2018;20:42-9.
Nichols GA, Hillier TA, Erbey JR, Brown JB. Congestive heart failure in type 2 diabetes: prevalence, incidence, and risk factors. Diabetes Care. 2001;24:1614-9.
Scheen AJ. GLP-1 receptor agonists and heart failure in diabetes. Diabetes Metab. 2017;43 Suppl 1:2S13-2S19.
Jorsal A, Kistorp C, Holmager P, Tougaard RS, Nielsen R, Hänselmann A, et al. Effect of liraglutide, a glucagon-like peptide-1 analogue, on left ventricular function in stable chronic heart failure patients with and without diabetes (LIVE) - a multicentre, double-blind, randomised, placebo-controlled trial. Eur J Heart Fail. 2017;19:69-77.
Marso SP, Bain SC, Consoli A, Eliaschewitz FG, Jódar E, Leiter LA, et al.; SUSTAIN-6 Investigators. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2016;375:1834-44.
Marso SP, Daniels GH, Brown-Frandsen K, Kristensen P, Mann JF, Nauck MA, et al.; LEADER Steering Committee; LEADER Trial Investigators. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375:311-22.
Husain M, Birkenfeld AL, Donsmark M, Dungan K, Eliaschewitz FG, Franco DR, et al.; PIONEER 6 Investigators. Oral semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2019;381:841-51.
Pfeffer MA, Claggett B, Diaz R, Dickstein K, Gerstein HC, Køber LV, et al.; ELIXA Investigators. Lixisenatide in patients with type 2 diabetes and acute coronary syndrome. N Engl J Med. 2015;373:2247-57.
Holman RR, Bethel MA, Mentz RJ, Thompson VP, Lokhnygina Y, Buse JB, et al.; EXSCEL Study Group. Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2017;377:1228-39.
Marso SP, Baeres FMM, Bain SC, Goldman B, Husain M, Nauck MA, et al.; LEADER Trial Investigators. Effects of liraglutide on cardiovascular outcomes in patients with diabetes with or without heart failure. J Am Coll Cardiol. 2020;75:1128-41.
Fudim M, White J, Pagidipati NJ, Lokhnygina Y, Wainstein J, Murin J, et al. Effect of once-weekly exenatide in patients with type 2 diabetes mellitus with and without heart failure and heart failure related outcomes: insights from the EXSCEL trial. Circulation. 2019;140:1613-22.
Juhaeri J, Gao S, Dai WS. Incidence rates of heart failure, stroke, and acute myocardial infarction among type 2 diabetic patients using insulin glargine and other insulin. Pharmacoepidemiol Drug Saf. 2009;18:497-503.
McAllister DA, Read SH, Kerssens J, Livingstone S, McGurnaghan S, Jhund P, et al. Incidence of hospitalization for heart failure and case-fatality among 3.25 million people with and without diabetes mellitus. Circulation. 2018;138:2774-86.
