Jonathan D Newman1, Rebecca Anthopolos1, G B John Mancini2, Sripal Bangalore1, Harmony R Reynolds1, Dennis F Kunichoff1, Roxy Senior3, Jesus Peteiro4, Balram Bhargava5, Pallav Garg6, Jorge Escobedo7, Rolf Doerr8, Tomasz Mazurek9, Jose Gonzalez-Juanatey10, Grzegorz Gajos11, Carlo Briguori12, Hong Cheng13, Andras Vertes14, Sandeep Mahajan5, Luis A Guzman15, Matyas Keltai16, Aldo P Maggioni17, Gregg W Stone18, Jeffrey S Berger1, Yves D Rosenberg19, William E Boden20, Bernard R Chaitman21, Jerome L Fleg19, Judith S Hochman, David J Maron22. 1. New York University Grossman School of Medicine (J.D.N., R.A., S.B., H.R.R., D.F.K., J.S.H.). 2. Center for Cardiovascular Innovation, University of British Columbia, Vancouver, Canada (G.B.J.M.). 3. Northwick Park Hospital-Royal Brompton Hospital, London, UK (R.S.). 4. Complejo Hospitalario Universitario de A Coruña (CHUAC), Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Universidad de A Coruña, A Coruña, Spain (J.P.). 5. All India Institute of Medical Sciences, Delhi (B.B., S.M.). 6. London Health Sciences Center, Western University, Ontario, Canada (P.G.). 7. Instituto Mexicano del Seguro Social, Mexico City (J.E.). 8. Praxisklinik Herz und Gefaesse, Dresden, Germany (R.D.). 9. Medical University of Warsaw, Poland (T.M.). 10. Cardiology Department, Hospital Clínico Universitario, Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares Institution, Spain (J.G-J.). 11. Department of Coronary Disease and Heart Failure, Faculty of Medicine, Jagiellonian University Medical College, Kraków, Poland (G.G.). 12. Laboratory of Interventional Cardiology and Department of Cardiology, Mediterranea Cardiocentro, Naples, Italy (C.B.). 13. Beijing Anzhen Hospital, Capital Medical University, China (H.C.). 14. Dél-pesti Centrumkóház Hospital, National Institute of Hematology and Infectious Disease, Cardiovascular Department, Budapest, Hungary (A.V.). 15. Instituto Médico Docencia Asistencia Médica e Investigación Clínica, Cordoba, Argentina (L.A.G.). 16. Semmelweis University, Budapest, Hungary (M.K.). 17. Associazione Nazionale Medici Cardiologi Ospedalieri Research Center, Florence, Italy (A.P.M.). 18. The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, Cardiovascular Research Foundation, New York (G.W.S.). 19. National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD (Y.D.R., J.L.F.). 20. Veterans Affairs New England Healthcare System, Boston University School of Medicine, MA (W.E.B.). 21. St Louis University School of Medicine Center for Comprehensive Cardiovascular Care, MO (B.R.C.). 22. Department of Medicine, Stanford University, CA (D.J.M.).
Abstract
BACKGROUND: Among patients with diabetes and chronic coronary disease, it is unclear if invasive management improves outcomes when added to medical therapy. METHODS: The ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trials (ie, ISCHEMIA and ISCHEMIA-Chronic Kidney Disease) randomized chronic coronary disease patients to an invasive (medical therapy + angiography and revascularization if feasible) or a conservative approach (medical therapy alone with revascularization if medical therapy failed). Cohorts were combined after no trial-specific effects were observed. Diabetes was defined by history, hemoglobin A1c ≥6.5%, or use of glucose-lowering medication. The primary outcome was all-cause death or myocardial infarction (MI). Heterogeneity of effect of invasive management on death or MI was evaluated using a Bayesian approach to protect against random high or low estimates of treatment effect for patients with versus without diabetes and for diabetes subgroups of clinical (female sex and insulin use) and anatomic features (coronary artery disease severity or left ventricular function). RESULTS: Of 5900 participants with complete baseline data, the median age was 64 years (interquartile range, 57-70), 24% were female, and the median estimated glomerular filtration was 80 mL·min-1·1.73-2 (interquartile range, 64-95). Among the 2553 (43%) of participants with diabetes, the median percent hemoglobin A1c was 7% (interquartile range, 7-8), and 30% were insulin-treated. Participants with diabetes had a 49% increased hazard of death or MI (hazard ratio, 1.49 [95% CI, 1.31-1.70]; P<0.001). At median 3.1-year follow-up the adjusted event-free survival was 0.54 (95% bootstrapped CI, 0.48-0.60) and 0.66 (95% bootstrapped CI, 0.61-0.71) for patients with diabetes versus without diabetes, respectively, with a 12% (95% bootstrapped CI, 4%-20%) absolute decrease in event-free survival among participants with diabetes. Female and male patients with insulin-treated diabetes had an adjusted event-free survival of 0.52 (95% bootstrapped CI, 0.42-0.56) and 0.49 (95% bootstrapped CI, 0.42-0.56), respectively. There was no difference in death or MI between strategies for patients with diabetes versus without diabetes, or for clinical (female sex or insulin use) or anatomic features (coronary artery disease severity or left ventricular function) of patients with diabetes. CONCLUSIONS: Despite higher risk for death or MI, chronic coronary disease patients with diabetes did not derive incremental benefit from routine invasive management compared with initial medical therapy alone. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01471522.
BACKGROUND: Among patients with diabetes and chronic coronary disease, it is unclear if invasive management improves outcomes when added to medical therapy. METHODS: The ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trials (ie, ISCHEMIA and ISCHEMIA-Chronic Kidney Disease) randomized chronic coronary disease patients to an invasive (medical therapy + angiography and revascularization if feasible) or a conservative approach (medical therapy alone with revascularization if medical therapy failed). Cohorts were combined after no trial-specific effects were observed. Diabetes was defined by history, hemoglobin A1c ≥6.5%, or use of glucose-lowering medication. The primary outcome was all-cause death or myocardial infarction (MI). Heterogeneity of effect of invasive management on death or MI was evaluated using a Bayesian approach to protect against random high or low estimates of treatment effect for patients with versus without diabetes and for diabetes subgroups of clinical (female sex and insulin use) and anatomic features (coronary artery disease severity or left ventricular function). RESULTS: Of 5900 participants with complete baseline data, the median age was 64 years (interquartile range, 57-70), 24% were female, and the median estimated glomerular filtration was 80 mL·min-1·1.73-2 (interquartile range, 64-95). Among the 2553 (43%) of participants with diabetes, the median percent hemoglobin A1c was 7% (interquartile range, 7-8), and 30% were insulin-treated. Participants with diabetes had a 49% increased hazard of death or MI (hazard ratio, 1.49 [95% CI, 1.31-1.70]; P<0.001). At median 3.1-year follow-up the adjusted event-free survival was 0.54 (95% bootstrapped CI, 0.48-0.60) and 0.66 (95% bootstrapped CI, 0.61-0.71) for patients with diabetes versus without diabetes, respectively, with a 12% (95% bootstrapped CI, 4%-20%) absolute decrease in event-free survival among participants with diabetes. Female and male patients with insulin-treated diabetes had an adjusted event-free survival of 0.52 (95% bootstrapped CI, 0.42-0.56) and 0.49 (95% bootstrapped CI, 0.42-0.56), respectively. There was no difference in death or MI between strategies for patients with diabetes versus without diabetes, or for clinical (female sex or insulin use) or anatomic features (coronary artery disease severity or left ventricular function) of patients with diabetes. CONCLUSIONS: Despite higher risk for death or MI, chronic coronary disease patients with diabetes did not derive incremental benefit from routine invasive management compared with initial medical therapy alone. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01471522.
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