• Gilles R Dagenais, Lars Rydén, Lawrence A Leiter, Mark Lakshmanan, Leanne Dyal, Jeffrey L Probstfield, Charles Messan Atisso, Jonathan E Shaw, Ignacio Conget, William C Cushman, Patricio Lopez-Jaramillo, Fernando Lanas, Ernesto German Cordona Munoz, Valdis Pirags, Nana Pogosova, Jan Basile, Wayne H H Sheu, Theodora Temelkova-Kurktschiev, Peter J Raubenheimer, Matyas Keltai, Stephanie Hall, Prem Pais, Helen M Colhoun, Matthew C Riddle, and Hertzel C Gerstein.
• Clinical Research Center, Laval University, Quebec Heart and Lung Institute, 2725, chemin Ste-Foy, Quebec City, Qc, GIV 4G5, Canada. gilles.dagenais@criucpq.ulaval.ca.
• Cardiovasc Diabetol. 2020 Nov 25; 19 (1): 199.

BackgroundThe Researching cardiovascular Events with a Weekly INcretin in Diabetes (REWIND) double blind randomized trial demonstrated that weekly subcutaneous dulaglutide 1.5 mg, a glucagon like peptide-1 receptor agonist, versus matched placebo reduced the first outcome of major adverse cardiovascular event (MACE), cardiovascular death, nonfatal myocardial infarction or nonfatal stroke (594 versus 663 events) in 9901 persons with type 2 diabetes and either chronic cardiovascular disease or risk factors, and followed during 5.4 years. These findings were based on a time-to-first-event analysis and preclude relevant information on the burden of total major events occurring during the trial. This analysis reports on the total cardiovascular or fatal events in the REWIND participants METHODS: We compared the total incidence of MACE or non-cardiovascular deaths, and the total incidence of expanded MACE (MACE, unstable angina, heart failure or revascularization) or non-cardiovascular deaths between participants randomized to dulaglutide and those randomized to placebo. Incidences were expressed as number per 1000 person-years. Hazard ratios (HR) were calculated using the conditional time gap and proportional means models.ResultsParticipants had a mean age of 66.2 years, 46.3% were women and 31% had previous cardiovascular disease. During the trial there were 1972 MACE or non-cardiovascular deaths and 3673 expanded MACE or non-cardiovascular deaths. The incidence of total MACE or non-cardiovascular deaths in the dulaglutide and placebo groups was 35.8 and 40.3 per 1000 person-years, respectively [absolute reduction = 4.5 per 1000 person-years; conditional time gap HR 0.90 (95% CI, 0.82-0.98) p = 0.020, and proportional means HR 0.89 (95% CI, 0.80-0.98) p = 0.022]. The incidence of total expanded MACE or non-cardiovascular deaths in the dulaglutide and placebo groups was 67.1 and 74.7 per 1000 person-years, respectively [absolute reduction = 7.6 per 1000 person-years; conditional time gap HR 0.93 (95% CI, 0.87-0.99) p = 0.023, and proportional means HR 0.90 (95% CI, 0.82-0.99) p = 0.028].ConclusionsThese findings suggest that weekly subcutaneous dulaglutide reduced total cardiovascular or fatal event burden in people with type 2 diabetes at moderate cardiovascular risk.Clinical Trial Registrationhttps://www.clinicaltrials.gouv . Unique Identifier NCT01394952).

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