This project was supported in part by National Institutes of Health (NIH) grants U01HL105907, U01HL105462, U01HL105561, and U01HL105565; and Clinical Translational Science Award number UL1 TR001445 from the National Center for Advancing Translational Sciences. The contents of this project are solely the responsibility of the authors and do not necessarily represent official views of the National Center for Advancing Translational Sciences; the National Heart, Lung, and Blood Institute (NHLBI); the NIH; or the Department of Health and Human Services. Dr Leipsic is a consultant and has stock options HeartFlow and CIRCLE CVI; has received a research grant from GE Healthcare outside the submitted work. Mr Broderick has received grants from the NHLBI during the conduct of the study. Dr Mancini has received grants from NHLBI, during the conduct of the study; grants and personal fees from Amgen, Sanofi, Boerhinger Ingelheim, AstraZeneca, Bayer, Janssen, Novo Nordisk; grants from Novartis; and grants and personal fees from HLS Therapeutics, outside of the submitted work. Dr Rockhold has received research support from NIH, PCORI, BMS, AstraZeneca, American Regent, Gates Foundation, Eidos; consulting fees from Janssen, Clover, Doctor Evidence, Resolve, and Intercept; Data Safety Monitoring Board membership for Lilly, AstraZeneca, Merck, Gilead, Novartis, Icosavax, Sanofi, UCB, Amgen, Biogen, BMS, Pulmocide, Alkermes, Diurnal; is the nonprofit chairman of the board (unpaid) for Frontier Science Foundation; and stock/stock options from GSK, Clover, Athira, Doctor Evidence, DataVant, Spencer Health Solutions, and Adaptic Health. Dr Chaitman has received grants from NHLBI; and personal fees from Merck, NovoNordisk, Sanofi, Lilly, Johnson and Johnson, Daiichi Sankyo, Tricida, Relypsa, Imbria, and Xylocor outside of the submitted work. Dr Stone has received grants and personal fees from the NHLBI during the conduct of the study; speaker honoraria from Medtronic, Pulnovo, Infraredx, Abiomed, Amgen, and Boehringer Ingelheim; is a consultant to Abbott, Daiichi Sankyo, Ablative Solutions, CorFlow, Apollo Therapeutics, Cardiomech, Gore, Robocath, Miracor, Vectorious, Abiomed, Valfix, TherOx, HeartFlow, Neovasc, Ancora, Elucid Bio, Occlutech, Impulse Dynamics, Adona Medical, Millennia Biopharma, Oxitope, Cardiac Success, and HighLife; and has equity/options from Ancora, Cagent, Applied Therapeutics, Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, Valfix, and Xenter. Dr Stone’s employer, Mount Sinai Hospital, has received research grants from Abbott, Abiomed, Bioventrix, Cardiovascular Systems Inc, Phillips, Biosense-Webster, Shockwave, Vascular Dynamics, Pulnovo and V-wave. Dr Stone’s daughter is an employee at IQVIA. Dr Ali has received grants from NHLBI, during the conduct of the study; grants and personal fees from Abbott Vascular and Cardiovascular Systems Inc; personal fees from Amgen, AstraZeneca, Abiomed, Boston Scientific, Cardinal Health, Opsens Medical, and Acist Medical; and other from Shockwave Medical, outside of the submitted work. Dr Min has received grants from NHLBI, during the conduct of the study; other from Cleerly Inc; grants and other from GE Healthcare; and other from Arineta, outside of the submitted work. Dr Hochman is the PI for the ISCHEMIA trials for which, in addition to support by NHLBI grant, devices and medications were provided by Abbott Vascular, Medtronic, Inc, Abbott Laboratories (formerly St. Jude Medical, Inc), Royal Philips NV (formerly Volcano Corporation), Arbor Pharmaceuticals, LLC, AstraZeneca Pharmaceuticals, LP, Merck Sharp & Dohme Corp, Omron Healthcare, Inc, Sunovion Pharmaceuticals, Inc, Espero BioPharma, and Amgen, Inc; financial donations from Arbor Pharmaceuticals LLC and AstraZeneca Pharmaceuticals LP; and is the PI for ISCHEMIA-EXTEND. Dr Maron has received grants from NHLBI, during the conduct of the study. Dr Reynolds has received grants from NHLBI, during the conduct of the study; and support from Abbott Vascular (donation of optical coherence tomography catheters for an unrelated research study) and Biotelemetry Inc (donation of telemetry monitors for an unrelated research study). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches [ISCHEMIA]; NCT01471522).