1. Diabetes-Related Factors and the Effects of Ticagrelor Plus Aspirin in the THEMIS and THEMIS-PCI Trials
- Author
-
Darren K. McGuire, Jane J. Lee, Lawrence A. Leiter, Shamir R. Mehta, Yuyin Liu, Eli I. Lev, Tabassome Simon, Investigators, Mikhail Kosiborod, John Amerena, Wilhelm Ridderstråle, Róbert Gábor Kiss, Philippe Gabriel Steg, Héctor Bueno, Jayne Prats, Deepak L. Bhatt, Kim Fox, Anthony J. Dalby, Hwee Teoh, Anders Himmelmann, Keenan Research Centre of the Li Ka Shing Knowledge Institute [Toronto], University of Toronto, Harvard Medical School [Boston] (HMS), University of Texas Southwestern Medical Center [Dallas], Royal Brompton Hospital, National Heart and Lung Institute [London] (NHLI), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, Service de Pharmacologie clinique [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), McMaster University [Hamilton, Ontario], Ben-Gurion University of the Negev (BGU), Hospital Universitario 12 de Octubre [Madrid], Centro Nacional de Investigaciones Cardiovasculares Carlos III [Madrid, Spain] (CNIC), Instituto de Salud Carlos III [Madrid] (ISC), AstraZeneca, Baim Institute for Clinical Research Boston MA, University of Missouri [Kansas City] (UMKC), University of Missouri System, The George Institute for Global Health [Sydney] (GIGH), The University of Sydney, University of New South Wales [Sydney] (UNSW), Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord
- Subjects
Male ,Ticagrelor ,Cardiac & Cardiovascular Systems ,THEMIS Steering Committee and Investigators ,[SDV]Life Sciences [q-bio] ,Coronary Artery Disease ,030204 cardiovascular system & hematology ,DISEASE ,MELLITUS ,0302 clinical medicine ,030212 general & internal medicine ,1102 Cardiorespiratory Medicine and Haematology ,RISK ,COMPLICATIONS ,Aspirin ,3. Good health ,Treatment Outcome ,CLOPIDOGREL ,diabetes mellitus ,HEART-FAILURE ,Drug Therapy, Combination ,Female ,Cardiology and Cardiovascular Medicine ,Life Sciences & Biomedicine ,medicine.drug ,medicine.medical_specialty ,aspirin ,Health outcomes ,1117 Public Health and Health Services ,03 medical and health sciences ,Percutaneous Coronary Intervention ,Diabetes mellitus ,Internal medicine ,medicine ,Humans ,cardiovascular diseases ,Retrospective Studies ,Related factors ,Science & Technology ,ANTIPLATELET THERAPY ,business.industry ,bleeding ,medicine.disease ,dual antiplatelet therapy ,PREVENTION ,Intervention studies ,ATHEROTHROMBOSIS ,MYOCARDIAL-INFARCTION ,Diabetes Mellitus, Type 2 ,Cardiovascular System & Hematology ,Conventional PCI ,Cardiovascular System & Cardiology ,business ,Platelet Aggregation Inhibitors ,Follow-Up Studies - Abstract
International audience; BACKGROUND THEMIS (The Effect of Ticagrelor on Health Outcomes in Diabetes Mellitus Patients Intervention Study) (n ¼ 19,220) and its pre-specified THEMIS-PCI (The Effect of Ticagrelor on Health Outcomes in Diabetes Mellitus Patients Intervention Study-Percutaneous Coronary Intervention) (n ¼ 11,154) subanalysis showed, in individuals with type 2 diabetes mellitus (median duration 10.0 years; HbA 1c 7.1%) and stable coronary artery disease without prior myocardial infarction (MI) or stroke, that ticagrelor plus aspirin (compared with placebo plus aspirin) produced a favorable net clinical benefit (composite of all-cause mortality, MI, stroke, fatal bleeding, and intracranial bleeding) if the patients had a previous percutaneous coronary intervention. OBJECTIVES In these post hoc analyses, the authors examined whether the primary efficacy outcome (cardiovascular death, MI, stroke: 3-point major adverse cardiovascular events [MACE]), primary safety outcome (Thrombolysis In Myocardial Infarction-defined major bleeding) and net clinical benefit varied with diabetes-related factors. METHODS Outcomes were analyzed across baseline diabetes duration, HbA 1c , and antihyperglycemic medications. RESULTS In THEMIS, the incidence of 3-point MACE increased with diabetes duration (6.7% for #5 years, 11.1% for >20 years) and HbA 1c (6.4% for #6.0%, 11.8% for >10.0%). The relative benefits of ticagrelor plus aspirin on 3-point MACE reduction (hazard ratio [HR]: 0.90; p ¼ 0.04) were generally consistent across subgroups. Major bleeding event rate (overall: 1.6%) did not vary by diabetes duration or HbA 1c and was increased similarly by ticagrelor across all subgroups (HR: 2.32; p < 0.001). These findings were mirrored in THEMIS-PCI. The efficacy and safety of ticagrelor plus aspirin did not differ by baseline antihyperglycemic therapy. In THEMIS-PCI, but not THEMIS, ticagrelor generally produced favorable net clinical benefit across diabetes duration, HbA 1c , and antihyperglycemic medications. CONCLUSION Ticagrelor plus aspirin yielded generally consistent and favorable net clinical benefit across the diabetesrelated factors in THEMIS-PCI but not in the overall THEMIS population.
- Published
- 2021
- Full Text
- View/download PDF