@article{16972fd3f8124909b78c85e4b94d3f6e,
title = "Cardiovascular and renal benefits of dapagliflozin in patients with short and long-standing type 2 diabetes: Analysis from the DECLARE-TIMI 58 trial",
abstract = "Aim: To investigate whether the cardiovascular and renal benefits observed with dapagliflozin in the DECLARE-TIMI 58 trial are also observed in patients with short and long-standing diabetes. Materials and Methods: This post hoc analysis studied the dual primary efficacy endpoints, a composite of cardiovascular death or hospitalization for heart failure (CVD/HHF) and major adverse cardiovascular events (MACE; CVD, myocardial infarction [MI], ischaemic stroke) by diabetes duration. Results: Of the 17 160 patients, 3836 had diabetes duration of ≤5 years, 4731 >5-10 years, 3952 >10-15 years, 2433 >15-20 years and 2206 >20 years. Dapagliflozin reduced the risk of CVD/HHF by a similar amount across diabetes duration subgroups, ranging from HR 0.79 (0.58-1.06) in patients with diabetes duration of ≤5 years to 0.75 (0.55-1.03) in those patients with diabetes duration of >20 years (interaction trend P-value 0.76). Hazard ratios (HRs) for MACE ranged from 1.08 (0.87-1.35) in patients with diabetes duration of ≤5 years to 0.67 (0.52-0.86) in those patients with diabetes duration of >20 years (interaction trend P-value 0.004). This was driven by greater reductions in the risk of MI and ischaemic stroke with dapagliflozin in patients with long-standing diabetes (interaction trend P-values 0.019 and 0.015, respectively). The duration-based MACE heterogeneity was apparent in those with or without a history of prior MI and in those with multiple risk factors. The renal-specific outcome was reduced with dapagliflozin with HRs ranging from 0.79 (0.47-1.34) in patients with diabetes duration of ≤5 years to 0.42 (0.25-0.72) in those patients with diabetes duration of >20 years (interaction trend P-value 0.084). Conclusions: Dapagliflozin reduced the risk of CVD/HHF consistently, regardless of diabetes duration, whereas the treatment effect for MACE differed by duration subgroups, with significant reductions with dapagliflozin in patients with long-standing diabetes.",
keywords = "cardiovascular disease, dapagliflozin, diabetes duration, major adverse cardiovascular events, sodium-glucose co-transporter-2 inhibitors, type 2 diabetes",
author = "Bajaj, {Harpreet S.} and Itamar Raz and Ofri Mosenzon and Murphy, {Sabina A.} and Aliza Rozenberg and Ilan Yanuv and Bhatt, {Deepak L.} and Leiter, {Lawrence A.} and McGuire, {Darren K.} and Wilding, {John P.H.} and Gause-Nilsson, {Ingrid A.M.} and Sabatine, {Marc S.} and Wiviott, {Stephen D.} and Avivit Cahn",
note = "Funding Information: The DECLARE ‐ TIMI 58 trial was funded by AstraZeneca Funding information Funding Information: HSB reports personal fees for lectures and research funding for serving as principal investigator on clinical trials paid to LMC Healthcare from Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, Novo Nordisk and Sanofi; he serves as an editor for the and as a columnist for Medscape. IR reports personal fees from AstraZeneca, Bristol‐Myers Squibb, Boehringer Ingelheim, Concenter BioPharma and Silkim, Eli Lilly, Merck Sharp & Dohme, Novo Nordisk, Orgenesis, Pfizer, Sanofi, SmartZyme Innovation, Panaxia, FuturRx, Insuline Medical, Medial EarlySign, CameraEyes, Exscopia, Dermal Biomics, Johnson & Johnson, Novartis, Teva, GlucoMe and DarioHealth. OM reports grants and personal fees from AstraZeneca, Bristol‐Myers Squibb, and Novo Nordisk and personal fees from Eli Lilly, Sanofi, Merck Sharp & Dohme, Boehringer Ingelheim, Johnson & Johnson and Novartis. SAM reports research grant support through Brigham and Women's Hospital from Abbott, Amgen, Aralez, AstraZeneca, Bayer HealthCare Pharmaceuticals, Inc., Daiichi‐Sankyo, Eisai, GlaxoSmithKline, Intarcia, Janssen, MedImmune, Merck, Novartis, Pfizer, Poxel, Quark Pharmaceuticals, Roche, Takeda, The Medicines Company and Zora Biosciences. AR and IY declare no competing interests. DLB discloses the following relationships – Advisory Board: Cardax, Cereno Scientific, Elsevier Practice Update Cardiology, Medscape Cardiology, PhaseBio, PLx Pharma and Regado Biosciences; Board of Directors: Boston VA Research Institute, Society of Cardiovascular Patient Care and TobeSoft; Chair: American Heart Association Quality Oversight Committee; Data Monitoring Committees: Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Cleveland Clinic (including for the ExCEED trial, funded by Edwards), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo) and Population Health Research Institute; Honoraria: American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org ; Vice‐Chair, ACC Accreditation Committee), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE‐DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS‐II executive committee funded by CSL Behring), Belvoir Publications (Editor‐in‐Chief, ), Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor‐in‐Chief, ), (Guest Editor; Associate Editor), Medtelligence/ReachMD (CME steering committees), Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co‐leader, funded by Bayer), Slack Publications (Chief Medical Editor, ), Society of Cardiovascular Patient Care (Secretary/Treasurer) and WebMD (CME steering committees); Other: (Deputy Editor), NCDR‐ACTION Registry Steering Committee (Chair) and VA CART Research and Publications Committee (Chair); Research Funding: Abbott, Afimmune, Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol‐Myers Squibb, Cardax, Chiesi, CSL Behring, Eisai, Ethicon, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Idorsia, Ironwood, Ischemix, Lexicon, Lilly, Medtronic, Pfizer, PhaseBio, PLx Pharma, Regeneron, Roche, Sanofi Aventis, Synaptic and The Medicines Company; Royalties: Elsevier (Editor, ); Site Co‐Investigator: Biotronik, Boston Scientific, CSI, St. Jude Medical (now Abbott) and Svelte; Trustee: American College of Cardiology; and Unfunded Research: FlowCo, Merck, Novo Nordisk and Takeda. LAL reports grants and personal fees from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Novo Nordisk and Sanofi; personal fees from Merck and Servier; and grants from GlaxoSmithKline. DKM discloses the following relationships: personal fees for clinical trial leadership from GlaxoSmithKline, Janssen, Lexicon AstraZeneca, Sanofi Aventis, Boehringer Ingelheim, Merck & Co, Pfizer, Novo Nordisk, Eisai Inc., Esperion and Lilly USA; and personal fees for consultancy from AstraZeneca, Lilly USA, Boehringer Ingelheim, Merck & Co, Novo Nordisk, Metavant, Applied Therapeutics, Sanofi Aventis and Afimmune. JPHW, outside the submitted work, has grants, personal fees for lectures and consultancy fees (paid to his institution) from AstraZeneca and Novo Nordisk; personal fees for lectures and consultancy fees (paid to his institution) from Boehringer Ingelheim, Janssen, Lilly, Mundipharma, Napp, Sanofi and Takeda; and consultancy fees (paid to his institution) from Rhythm Pharmaceuticals and Wilmington Healthcare. IAMG‐N is an employee of AstraZeneca. MSS reports grants and consulting fees from Amgen, consulting fees from Anthos Therapeutics, grants and consulting fees from AstraZeneca, grants from Bayer, consulting fees from Bristol‐Myers Squibb, consulting fees from CVS Caremark, grants from Daiichi‐Sankyo, consulting fees from DalCor, consulting fees from Dyrnamix, grants from Eisai, consulting fees from Esperion, grants from GlaxoSmithKline, consulting fees from IFM Therapeutics, grants and consulting fees from Intarcia, consulting fees from Ionis, grants and consulting fees from Janssen Research and Development, grants and consulting fees from Medicines Company, grants and consulting fees from MedImmune, grants and consulting fees from Merck, grants and consulting fees from Novartis, grants from Pfizer, grants from Poxel, grants from Quark Pharmaceuticals, grants from Takeda, and is a member of the TIMI Study Group, which has also received institutional research grant support through Brigham and Women's Hospital from Abbott, Aralez, Roche and Zora Biosciences. SDW discloses grants from AstraZeneca, Bristol‐Myers Squibb, Sanofi Aventis, and Amgen; grants and personal fees from Arena, Daiichi Sankyo, Eisai, Eli Lilly and Janssen; grants and consulting fees from Merck (additionally his spouse is employed by Merck); and personal fees from Aegerion, Allergan, AngelMed, Boehringer Ingelheim, Boston Clinical Research Institute, Icon Clinical, Lexicon, St Jude Medical, Xoma, Servier, AstraZeneca and Bristol‐Myers Squibb. AC reports grants and personal fees from AstraZeneca and Novo Nordisk and personal fees from Abbott, Eli Lilly, Sanofi, Boehringer Ingelheim, Merck Sharp & Dohme, and is a consultant for Medial Early‐Sign and GlucoMe. Canadian Journal of Diabetes Harvard Heart Letter Journal of Invasive Cardiology Journal of the American College of Cardiology Cardiology Today's Intervention Clinical Cardiology Cardiovascular Intervention: A Companion to Braunwald's Heart Disease Publisher Copyright: {\textcopyright} 2020 John Wiley & Sons Ltd",
year = "2020",
month = jul,
day = "1",
doi = "10.1111/dom.14011",
language = "English (US)",
volume = "22",
pages = "1122--1131",
journal = "Diabetes, Obesity and Metabolism",
issn = "1462-8902",
publisher = "Wiley-Blackwell",
number = "7",
}