PMID- 37344040 OWN - NLM STAT- MEDLINE DCOM- 20230623 LR - 20230625 IS - 1558-3597 (Electronic) IS - 0735-1097 (Linking) VI - 81 IP - 25 DP - 2023 Jun 27 TI - Assessment of Atherothrombotic Risk in Patients With Type 2 Diabetes Mellitus. PG - 2391-2402 LID - S0735-1097(23)05500-6 [pii] LID - 10.1016/j.jacc.2023.04.031 [doi] AB - BACKGROUND: Risk of atherothrombotic events is not uniform in patients with type 2 diabetes mellitus (T2DM). Tailored risk assessment may help guide selection of pharmacotherapies for cardiovascular primary and secondary prevention. OBJECTIVES: The purpose of this study was to develop a risk model for atherothrombosis in patients with T2DM. METHODS: We developed and validated a risk model for myocardial infarction (MI) or ischemic stroke (IS) in a pooled cohort of 42,181 patients with T2DM from 4 TIMI (Thrombolysis In Myocardial Infarction) clinical trial cohorts. Candidate variables were assessed with multivariable Cox regression, and independent variables (P < 0.05) were retained in the final model. Discrimination and calibration were assessed. Treatment interactions with dapagliflozin (sodium-glucose cotransporter-2 inhibitor) and evolocumab (proprotein convertase subtilisin/kexin type 9 inhibitor) were explored in the DECLARE-TIMI 58 (Dapagliflozin Effect on CardiovascuLAR Events-Thrombolysis In Myocardial Infarction 58) and FOURIER (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk) trials, respectively. RESULTS: Sixteen variables were independent predictors of MI or IS. The model identified a >8-fold gradient of MI or IS rates between the top vs bottom risk quintiles in the validation cohort (3-year Kaplan-Meier rate: 14.9% vs 1.4%; P < 0.0001). C-indexes were 0.704 and 0.706 in the derivation and validation cohorts, respectively. The model was well-calibrated in both primary and secondary prevention. Absolute reduction in the rates of MI or IS tended to be greater in patients with higher baseline predicted risk for both dapagliflozin (absolute risk reduction: 2.1% vs 0.2%) and evolocumab (absolute risk reduction: 3.2% vs 1.0%). CONCLUSIONS: We developed and validated a risk score for atherothrombotic events, leveraging 16 routinely assessed clinical variables in patients with T2DM. The score has the potential to improve risk assessment and inform clinical decision-making. CI - Copyright (c) 2023 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Berg, David D AU - Berg DD AD - TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. Electronic address: dberg1@bwh.harvard.edu. FAU - Moura, Filipe A AU - Moura FA AD - TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. FAU - Bellavia, Andrea AU - Bellavia A AD - TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. FAU - Scirica, Benjamin M AU - Scirica BM AD - TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. FAU - Wiviott, Stephen D AU - Wiviott SD AD - TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. FAU - Bhatt, Deepak L AU - Bhatt DL AD - Mount Sinai Heart, Icahn School of Medicine at Mount Sinai Health System, New York, New York, USA. FAU - Raz, Itamar AU - Raz I AD - Faculty of Medicine, Hadassah Hebrew University Hospital, Jerusalem, Israel. FAU - Bohula, Erin A AU - Bohula EA AD - TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. FAU - Giugliano, Robert P AU - Giugliano RP AD - TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. FAU - Park, Jeong-Gun AU - Park JG AD - TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. FAU - Feinberg, Mark W AU - Feinberg MW AD - Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. FAU - Braunwald, Eugene AU - Braunwald E AD - TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. FAU - Morrow, David A AU - Morrow DA AD - TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. FAU - Sabatine, Marc S AU - Sabatine MS AD - TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Am Coll Cardiol JT - Journal of the American College of Cardiology JID - 8301365 RN - EC 3.4.21.- (PCSK9 protein, human) RN - 1ULL0QJ8UC (dapagliflozin) RN - EC 3.4.21.- (Proprotein Convertase 9) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM CIN - J Am Coll Cardiol. 2023 Jun 27;81(25):2403-2405. PMID: 37344041 MH - Humans MH - *Diabetes Mellitus, Type 2/complications/drug therapy/epidemiology MH - Proprotein Convertase 9 MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Myocardial Infarction/complications MH - Risk Assessment OTO - NOTNLM OT - atherothrombosis OT - clinical trials OT - diabetes mellitus OT - ischemic stroke OT - myocardial infarction COIS- Funding Support and Author Disclosures The SAVOR-TIMI 53 and DECLARE-TIMI 58 trials were supported by institutional research grants to Brigham and Women's Hospital from AstraZeneca. The FOURIER trial was supported by an institutional research grant to Brigham and Women's Hospital from Amgen. The CAMELLIA-TIMI 61 trial was supported by an institutional research grant to Brigham and Women's Hospital from Eisai. Drs Berg, Moura, Scirica, Wiviott, Feinberg, Morrow, and Sabatine were supported for the present analysis by the American Heart Association Cardiometabolic Health and Type 2 Diabetes Mellitus Strategically Focused Research Network (20SFRN35120087). Drs Berg, Moura, Bellavia, Scirica, Wiviott, Bohula, Giugliano, Park, Braunwald, Morrow, and Sabatine are members of the TIMI Study Group, which has received institutional research grant support through Brigham and Women's Hospital from Abbott, Abiomed, Amgen, Anthos Therapeutics, ARCA Biopharma, Inc, AstraZeneca, Bayer HealthCare Pharmaceuticals, Daiichi-Sankyo, Eisai, Intarcia, Ionis Pharmaceuticals, Janssen Research and Development, MedImmune, Merck, Novartis, Pfizer, Quark Pharmaceuticals, Regeneron Pharmaceuticals, Roche, Siemens Healthcare Diagnostics, Softcell Medical Limited, The Medicines Company, and Zora Biosciences. Dr Berg has received research grant support to his institution from AstraZeneca and Pfizer; has received consulting fees from AstraZeneca, Mobility Bio, Inc, and Youngene Therapeutics; has received honoraria from the Medical Education Speakers Network (MESN) and USV Private Limited; and participates on clinical endpoint committees for studies sponsored by Kowa Pharmaceuticals. Dr Scirica has received institutional research grants to Brigham and Women's Hospital from Better Therapeutics, Merck, Novo Nordisk, and Pfizer; has received consulting fees from Allergan, Boehringer Ingelheim, Better Therapeutics, Elsevier Practice Update Cardiology, Esperion, Hanmi, Lexicon, and Novo Nordisk; and has equity in Health [at] Scale and Doximity. Dr Wiviott has received grants from Amgen, AstraZeneca, Daiichi-Sankyo, Eisai, Janssen, Merck, and Pfizer; has received consulting fees from AstraZeneca, Boston Clinical Research Institute, Icon Clinical, and Novo Nordisk; and his spouse is a former employee of Merck and is a current employee of Flagship Labs 86. Dr Bhatt has served on the Advisory Board of AngioWave, Bayer, Boehringer Ingelheim, Cardax, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, Regado Biosciences, and Stasys; has served on the Board of Directors of AngioWave (stock options), Boston VA Research Institute, Bristol Myers Squibb (stock), DRS.LINQ (stock options), High Enroll (stock), Society of Cardiovascular Patient Care, and TobeSoft; is Inaugural Chair of the American Heart Association Quality Oversight Committee; has served as a consultant for Broadview Ventures; has served on Data Monitoring Committees for Acesion Pharma, Assistance Publique-Hopitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St Jude Medical, now Abbott), Boston Scientific (Chair, PEITHO trial), Cleveland Clinic (including for the ExCEED trial, funded by Edwards), Contego Medical (Chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi-Sankyo; for the ABILITY-DM trial, funded by Concept Medical), Novartis, Population Health Research Institute, and Rutgers University (for the National Institutes of Health-funded MINT Trial); has received honoraria from the American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Chair, ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol Myers Squibb clopidogrel litigation), 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, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor-in-Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), K2P (Co-Chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Oakstone CME (Course Director, Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national coleader, funded by Bayer), Slack Publications (Chief Medical Editor, Cardiology Today's Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), WebMD (CME steering committees), and Wiley (steering committee); has served as Deputy Editor of Clinical Cardiology; is Chair of the NCDR-ACTION Registry Steering Committee and VA CART Research and Publications Committee; has a patent for Sotagliflozin (named on a patent for sotagliflozin assigned to Brigham and Women's Hospital who assigned to Lexicon; neither I nor Brigham and Women's Hospital receive any income from this patent); has received research funding from Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CinCor, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, Youngene, and 89Bio; has received royalties from Elsevier (Editor, Braunwald's Heart Disease); is site co-investigator for Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St. Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, and Vascular Solutions; is a Trustee of the American College of Cardiology; and has performed unfunded research for FlowCo and Takeda. Dr Raz has received personal fees from AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Concenter BioPharma and Silkim, Eli Lilly, Merck Sharp and Dohme, Novo Nordisk, Orgenesis, Pfizer, Sanofi, SmartZyme Innovation, Panaxia, FuturRx, InsuLine Medical, Medial EarlySign, CameraEyes, Exscopia, Dermal Biomics, Johnson and Johnson, Novartis, Teva, GlucoMe, and DarioHealth. Dr Bohula has received personal fees from Servier, Kowa, Medscape, Novo Nordisk, Amgen, PriMed, and Merck. Dr Giugliano has received research support from Amgen, Anthos Therapeutics, and Daiichi-Sankyo; has received honoraria for lectures/CME programs for Amgen, Centrix, Daiichi-Sankyo, Dr Reddy's Laboratories, Medical Education Resources, Medscape, Menarini, Merck, Pfizer, SAJA Pharmaceuticals, Servier, Shanghai Medical Telescope, and Voxmedia; and has received consultant fees from Amarin, Amgen, Boston Scientific, CryoLife, CSL Behring, CVS Caremark, Daiichi-Sankyo, Esperion, Gilead, Hengrui, Inari, Janssen, Novartis, Pfizer, PhaseBio Pharmaceuticals, St. Lukes, and Samsung. Dr Braunwald has received research grants through his institution from AstraZeneca, Daiichi-Sankyo, Merck, and Novartis; and has received consultancy fees from Amgen, Bristol Myers Squibb, Boehringer Ingelheim/Lilly, Cardurion, and Verve. Dr Morrow has received grants to the Brigham and Women's Hospital from Abbott Laboratories, Amgen, Anthos Therapeutics, AstraZeneca, Eisai, The Medicines Company, Merck, Novartis, Pfizer, Roche Diagnostics, and Siemens; and has received consultant fees from InCardia, Inflammatix, Merck and Co, Novartis, and Roche Diagnostics. Dr Sabatine has received research grant support through Brigham and Women's Hospital from Abbott, Amgen, Anthos Therapeutics, AstraZeneca, Daiichi-Sankyo, Eisai, Intarcia, Ionis, Merck, Novartis, and Pfizer; and has served as a consultant for Althera, Amgen, Anthos Therapeutics, AstraZeneca, Beren Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb, Fibrogen, Intarcia, Merck, Moderna, Novo Nordisk, and Silence Therapeutics. EDAT- 2023/06/22 01:07 MHDA- 2023/06/23 06:42 CRDT- 2023/06/21 20:57 PHST- 2023/02/10 00:00 [received] PHST- 2023/03/22 00:00 [revised] PHST- 2023/04/17 00:00 [accepted] PHST- 2023/06/23 06:42 [medline] PHST- 2023/06/22 01:07 [pubmed] PHST- 2023/06/21 20:57 [entrez] AID - S0735-1097(23)05500-6 [pii] AID - 10.1016/j.jacc.2023.04.031 [doi] PST - ppublish SO - J Am Coll Cardiol. 2023 Jun 27;81(25):2391-2402. doi: 10.1016/j.jacc.2023.04.031.