TY - JOUR
T1 - The design and rationale for the Dapagliflozin Effect on Cardiovascular Events (DECLARE)–TIMI 58 Trial
AU - Wiviott, Stephen D.
AU - Raz, Itamar
AU - Bonaca, Marc P.
AU - Mosenzon, Ofri
AU - Kato, Eri T.
AU - Cahn, Avivit
AU - Silverman, Michael G.
AU - Bansilal, Sameer
AU - Bhatt, Deepak L.
AU - Leiter, Lawrence A.
AU - McGuire, Darren K.
AU - Wilding, John PH
AU - Gause-Nilsson, Ingrid AM
AU - Langkilde, Anna Maria
AU - Johansson, Peter A.
AU - Sabatine, Marc S.
N1 - Funding Information:
Data analysis will be conducted in parallel between the Sponsor and the TIMI Study Group. The TIMI Study Group and The Hadassah Medical Organization will have complete access to the study database, and will submit results for presentation and publication of the primary results in a peer-reviewed medical journal. The trial was funded by and research grants for trial activities were provided to the Brigham and Women's Hospital (TIMI) and the Hadassah Medical Organization by AstraZeneca .
Funding Information:
Data analysis will be conducted in parallel between the Sponsor and the TIMI Study Group. The TIMI Study Group and The Hadassah Medical Organization will have complete access to the study database, and will submit results for presentation and publication of the primary results in a peer-reviewed medical journal. The trial was funded by and research grants for trial activities were provided to the Brigham and Women's Hospital (TIMI) and the Hadassah Medical Organization by AstraZeneca.
Funding Information:
Dr Cahn discloses the following relationships: Advisory Board: Novo Nordisk, Eli Lilly, Sanofi, Boehringer Ingelheim, AstraZeneca; research grant support through Hadassah Hebrew University Hospital: AstraZeneca; Speaker's Bureau: AstraZeneca, Novo Nordisk, Eli Lilly, Sanofi, Merck Sharp & Dohme, Boehringer Ingelheim. Stock/shareholder: Glucome Ltd.
Publisher Copyright:
© 2018
PY - 2018/6
Y1 - 2018/6
N2 - Background: Dapagliflozin is a sodium-glucose co-transporter-2 (SGLT-2) inhibitor that reduces blood glucose in patients with type 2 diabetes mellitus (T2DM) by promoting glycosuria via inhibiting urinary glucose reabsorption. In addition to improving blood glucose control, treatment with dapagliflozin results in glucose-induced osmotic diuresis, weight loss, and blood pressure lowering. Previous trials of SGLT-2 inhibitors showed reductions in cardiovascular (CV) events, including CV death and hospitalization for heart failure, and ischemic events in patients with atherosclerotic cardiovascular disease (ASCVD). Research design and methods: DECLARE–TIMI 58 (NCT01730534) is a phase 3b randomized, double-blind, placebo-controlled trial designed to evaluate the CV safety and efficacy of dapagliflozin that has completed randomization of 17,160 patients with T2DM and a history of either established ASCVD (n = 6,971) or multiple risk factors for ASCVD (n = 10,189). Patients were randomized in a 1:1 fashion to dapagliflozin 10 mg or matching placebo. The primary safety outcome is the time to the first event of the composite of CV death, myocardial infarction, or ischemic stroke (major adverse cardiovascular events; MACEs). The co-primary efficacy outcomes are the composite of CV death, myocardial infarction, or ischemic stroke and the composite of CV death or hospitalization for heart failure. This event-driven trial will continue until at least 1,390 subjects have a MACE outcome, thereby providing >99% power to test for the primary outcome of safety of dapagliflozin measured by rejecting the hypothesis that the upper bound of the CI >1.3 for the primary outcome of MACE, as well as 85% power to detect a 15% relative risk reduction in MACE and an estimated 87% power to detect a 20% reduction in the composite of CV death or hospitalization for heart failure at a 1-sided α level of.0231. Conclusion: The DECLARE–TIMI 58 trial is testing the hypotheses that dapagliflozin is safe (does not increase) and may reduce the occurrence of major CV events. DECLARE–TIMI 58 is the largest study to address this question with an SGLT-2 inhibitor in patients with T2DM and with established CV disease and without CV disease but with multiple risk factors.
AB - Background: Dapagliflozin is a sodium-glucose co-transporter-2 (SGLT-2) inhibitor that reduces blood glucose in patients with type 2 diabetes mellitus (T2DM) by promoting glycosuria via inhibiting urinary glucose reabsorption. In addition to improving blood glucose control, treatment with dapagliflozin results in glucose-induced osmotic diuresis, weight loss, and blood pressure lowering. Previous trials of SGLT-2 inhibitors showed reductions in cardiovascular (CV) events, including CV death and hospitalization for heart failure, and ischemic events in patients with atherosclerotic cardiovascular disease (ASCVD). Research design and methods: DECLARE–TIMI 58 (NCT01730534) is a phase 3b randomized, double-blind, placebo-controlled trial designed to evaluate the CV safety and efficacy of dapagliflozin that has completed randomization of 17,160 patients with T2DM and a history of either established ASCVD (n = 6,971) or multiple risk factors for ASCVD (n = 10,189). Patients were randomized in a 1:1 fashion to dapagliflozin 10 mg or matching placebo. The primary safety outcome is the time to the first event of the composite of CV death, myocardial infarction, or ischemic stroke (major adverse cardiovascular events; MACEs). The co-primary efficacy outcomes are the composite of CV death, myocardial infarction, or ischemic stroke and the composite of CV death or hospitalization for heart failure. This event-driven trial will continue until at least 1,390 subjects have a MACE outcome, thereby providing >99% power to test for the primary outcome of safety of dapagliflozin measured by rejecting the hypothesis that the upper bound of the CI >1.3 for the primary outcome of MACE, as well as 85% power to detect a 15% relative risk reduction in MACE and an estimated 87% power to detect a 20% reduction in the composite of CV death or hospitalization for heart failure at a 1-sided α level of.0231. Conclusion: The DECLARE–TIMI 58 trial is testing the hypotheses that dapagliflozin is safe (does not increase) and may reduce the occurrence of major CV events. DECLARE–TIMI 58 is the largest study to address this question with an SGLT-2 inhibitor in patients with T2DM and with established CV disease and without CV disease but with multiple risk factors.
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U2 - 10.1016/j.ahj.2018.01.012
DO - 10.1016/j.ahj.2018.01.012
M3 - Article
C2 - 29898853
AN - SCOPUS:85045458725
SN - 0002-8703
VL - 200
SP - 83
EP - 89
JO - American heart journal
JF - American heart journal
ER -