학술논문
Factors Associated With Coronary Angiography Performed Within 6 Months of Randomization to the Conservative Strategy in the ISCHEMIA Trial.
Document Type
Academic Journal
Author
Pracoń R; National Institute of Cardiology, Warsaw, Poland (R.P., W.R.).; Spertus JA; Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City (J.A.S.).; Broderick S; Duke Clinical Research Institute, Durham, NC (S. Broderick, F.W.R.).; Bangalore S; Cardiovascular Clinical Research Center, New York University Grossman School of Medicine (S. Bangalore, J.D.N., H.R.R., J.S.H.).; Rockhold FW; Duke Clinical Research Institute, Durham, NC (S. Broderick, F.W.R.).; Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC (F.W.R.).; Ruzyllo W; National Institute of Cardiology, Warsaw, Poland (R.P., W.R.).; Demchenko E; Almazov National Medical Research Centre, Saint Petersburg, Russia (E.D.).; Nageh T; Southend University Hospital, United Kingdom (T.N.).; Grossman GB; Moinhos de Vento Hospital, Porto Alegre, Brazil (G.B.G.).; Cardionuclear Clinic, Porto Alegre, Brazil (G.B.G.).; Mavromatis K; Emory University, Atlanta VA Healthcare System, GA (K.M.).; Manjunath CN; Sri Jayadeva Institute of Cardiovascular Sciences and Research, Bengaluru, India (C.N.M.).; Smanio PEP; Instituto Dante Pazzanese de Cardiologia, São Paulo, Brazil (P.E.P.S.).; Stone GW; Icahn School of Medicine at Mount Sinai, New York, NY (G.W.S.).; Mancini GBJ; Center for Cardiovascular Innovation, The University of British Columbia, Vancouver, Canada (G.B.J.M.).; Boden WE; VA New England Healthcare System, Boston University School of Medicine, MA (W.E.B.).; Newman JD; Cardiovascular Clinical Research Center, New York University Grossman School of Medicine (S. Bangalore, J.D.N., H.R.R., J.S.H.).; Reynolds HR; Cardiovascular Clinical Research Center, New York University Grossman School of Medicine (S. Bangalore, J.D.N., H.R.R., J.S.H.).; Hochman JS; Cardiovascular Clinical Research Center, New York University Grossman School of Medicine (S. Bangalore, J.D.N., H.R.R., J.S.H.).; Maron DJ; Department of Medicine, Stanford University, CA (D.J.M.).
Source
Publisher: Lippincott Williams & Wilkins Country of Publication: United States NLM ID: 101499602 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1941-7632 (Electronic) Linking ISSN: 19417640 NLM ISO Abbreviation: Circ Cardiovasc Interv Subsets: MEDLINE
Subject
Language
English
Abstract
Background: ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) did not find an overall reduction in cardiovascular events with an initial invasive versus conservative management strategy in chronic coronary disease; however, there were conservative strategy participants who underwent invasive coronary angiography early postrandomization (within 6 months). Identifying factors associated with angiography in conservative strategy participants will inform clinical decision-making in patients with chronic coronary disease.
Methods: Factors independently associated with angiography performed within 6 months of randomization were identified using Fine and Gray proportional subdistribution hazard models, including demographics, region of randomization, medical history, risk factor control, symptoms, ischemia severity, coronary anatomy based on protocol-mandated coronary computed tomography angiography, and medication use.
Results: Among 2591 conservative strategy participants, angiography within 6 months of randomization occurred in 8.7% (4.7% for a suspected primary end point event, 1.6% for persistent symptoms, and 2.6% due to protocol nonadherence) and was associated with the following baseline characteristics: enrollment in Europe versus Asia (hazard ratio [HR], 1.81 [95% CI, 1.14-2.86]), daily and weekly versus no angina (HR, 5.97 [95% CI, 2.78-12.86] and 2.63 [95% CI, 1.51-4.58], respectively), poor to fair versus good to excellent health status (HR, 2.02 [95% CI, 1.23-3.32]) assessed with Seattle Angina Questionnaire, and new/more frequent angina prerandomization (HR, 1.80 [95% CI, 1.34-2.40]). Baseline low-density lipoprotein cholesterol <70 mg/dL was associated with a lower risk of angiography (HR, 0.65 [95% CI, 0.46-0.91) but not baseline ischemia severity nor the presence of multivessel or proximal left anterior descending artery stenosis >70% on coronary computed tomography angiography.
Conclusions: Among ISCHEMIA participants randomized to the conservative strategy, angiography within 6 months of randomization was performed in <10% of patients. It was associated with frequent or increasing baseline angina and poor quality of life but not with objective markers of disease severity. Well-controlled baseline low-density lipoprotein cholesterol was associated with a reduced likelihood of angiography. These findings point to the importance of a comprehensive assessment of symptoms and a review of guideline-directed medical therapy goals when deciding the initial treatment strategy for chronic coronary disease.
Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01471522.
Competing Interests: Disclosures Dr Pracoń reports grants from the National Heart, Lung, and Blood Institute (NHLBI), during the conduct of the study. Dr Spertus reports grants from the NHLBI, during the conduct of the study; personal fees from Bayer, Novartis, AstraZeneca, Amgen, Janssen, and United Healthcare; grants from the American College of Cardiology; and personal fees from Blue Cross Blue Shield of Kansas City, outside the submitted work. In addition, Dr Spertus has a patent Copyright to the Seattle Angina Questionnaire with royalties paid and Equity in Health Outcomes Sciences. Dr Bangalore reports grants from the NHLBI, during the conduct of the study; grants and personal fees from Abbott; and personal fees from Biotronik, Pfizer, Amgen, and Reata outside the submitted work. Dr Rockhold receives research support from the National Institutes of Health, Patient-Centered Outcomes Research Institute (PCORI), BMS, AstraZeneca, American Regent, the Gates Foundation, and Eidos; consulting fees from Janssen, Clover, Doctor Evidence, Resolve, and Intercept; is on the data safety and monitoring boards (DSMBs) for Lilly, AstraZeneca, Merck, Gilead, Novartis, Icosavax, Sanofi, Union Chimique Belge (UCB), Amgen, Biogen, BMS, Pulmocide, Alkermes, and Diurnal; is the nonprofit chairman of the board (unpaid) of the Frontier Science Foundation; and has stock/stock options in GSK, Clover, Athira, Doctor Evidence, DataVant, Spencer Health Solutions, and Adaptic Health. Dr Mavromatis reports grants from the NHLBI; grants from NHLBI (Cardiovascular Inflammation Reduction Trial and GMCSF in PAD-3 trial [Granulocyte-Macrophage Stimulating Factor (GM-CSF) in Peripheral Arterial Disease (GPAD-3)]); grants from CSL Behring, St Jude’s Medical, Medtronic, DalCor Pharmaceuticals, AstraZeneca, Novartis, and Regeneron; and is a member of the American College of Cardiology and the Society of Cardiovascular Angiography and Interventions. Dr Manjunath reports grants from NHLBI during the conduct of the study. Dr Stone reports grants from NHLBI during the conduct of the study; has received speaker honoraria from Pulnovo and Infraredx; has served as a consultant to Valfix, TherOx, Robocath, HeartFlow, Ablative Solutions, Vectorious, Miracor, Neovasc, Abiomed, Ancora, Elucid Bio, Occlutech, CorFlow, Apollo Therapeutics, Impulse Dynamics, Vascular Dynamics, Shockwave, V-Wave, Cardiomech, Gore, and Amgen; 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 daughter is an employee at Medtronic. Dr Stone’s employer, Mount Sinai Hospital, receives research support from Abbott, Bioventrix, Cardiovascular Systems, Inc, Phillips, Biosense-Webster, Shockwave, Vascular Dynamics, and V-Wave. Dr Mancini reports grants from NHLBI, during the conduct of the study; grants and personal fees from Amgen, Sanofi, Boehringer Ingelheim, AstraZeneca, Bayer, Janssen, and Novo Nordisk; grants from Novartis; and grants and personal fees from HLS Therapeutics, outside the submitted work. Dr Boden reports grants from NHLBI, during the conduct of the study; grants from Abbvie, Amarin, and Amgen; and personal fees from Amgen, the Cleveland Clinic Clinical Coordinating Center, and Janssen, outside the submitted work. Dr Newman reports grants from NHLBI, during the conduct of the study. Dr Reynolds reports grants from NHLBI, during the conduct of the study, and receives 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). Dr Hochman is a primary investigator for the ISCHEMIA trial (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) 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 Corporation, Omron Healthcare, Inc, Sunovion Pharmaceuticals, Inc, Espero BioPharma, and Amgen, Inc, and financial donations from Arbor Pharmaceuticals LLC and AstraZeneca Pharmaceuticals LP. Dr Hochman is also a primary investigator for the ISCHEMIA-EXTEND trial (The International Study of Comparative Health Effectiveness With Medical and Invasive Approaches [ISCHEMIA] Extended Follow-Up). Dr Maron reports grants from NHLBI, during the conduct of the study. The other authors report no conflicts.
Methods: Factors independently associated with angiography performed within 6 months of randomization were identified using Fine and Gray proportional subdistribution hazard models, including demographics, region of randomization, medical history, risk factor control, symptoms, ischemia severity, coronary anatomy based on protocol-mandated coronary computed tomography angiography, and medication use.
Results: Among 2591 conservative strategy participants, angiography within 6 months of randomization occurred in 8.7% (4.7% for a suspected primary end point event, 1.6% for persistent symptoms, and 2.6% due to protocol nonadherence) and was associated with the following baseline characteristics: enrollment in Europe versus Asia (hazard ratio [HR], 1.81 [95% CI, 1.14-2.86]), daily and weekly versus no angina (HR, 5.97 [95% CI, 2.78-12.86] and 2.63 [95% CI, 1.51-4.58], respectively), poor to fair versus good to excellent health status (HR, 2.02 [95% CI, 1.23-3.32]) assessed with Seattle Angina Questionnaire, and new/more frequent angina prerandomization (HR, 1.80 [95% CI, 1.34-2.40]). Baseline low-density lipoprotein cholesterol <70 mg/dL was associated with a lower risk of angiography (HR, 0.65 [95% CI, 0.46-0.91) but not baseline ischemia severity nor the presence of multivessel or proximal left anterior descending artery stenosis >70% on coronary computed tomography angiography.
Conclusions: Among ISCHEMIA participants randomized to the conservative strategy, angiography within 6 months of randomization was performed in <10% of patients. It was associated with frequent or increasing baseline angina and poor quality of life but not with objective markers of disease severity. Well-controlled baseline low-density lipoprotein cholesterol was associated with a reduced likelihood of angiography. These findings point to the importance of a comprehensive assessment of symptoms and a review of guideline-directed medical therapy goals when deciding the initial treatment strategy for chronic coronary disease.
Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01471522.
Competing Interests: Disclosures Dr Pracoń reports grants from the National Heart, Lung, and Blood Institute (NHLBI), during the conduct of the study. Dr Spertus reports grants from the NHLBI, during the conduct of the study; personal fees from Bayer, Novartis, AstraZeneca, Amgen, Janssen, and United Healthcare; grants from the American College of Cardiology; and personal fees from Blue Cross Blue Shield of Kansas City, outside the submitted work. In addition, Dr Spertus has a patent Copyright to the Seattle Angina Questionnaire with royalties paid and Equity in Health Outcomes Sciences. Dr Bangalore reports grants from the NHLBI, during the conduct of the study; grants and personal fees from Abbott; and personal fees from Biotronik, Pfizer, Amgen, and Reata outside the submitted work. Dr Rockhold receives research support from the National Institutes of Health, Patient-Centered Outcomes Research Institute (PCORI), BMS, AstraZeneca, American Regent, the Gates Foundation, and Eidos; consulting fees from Janssen, Clover, Doctor Evidence, Resolve, and Intercept; is on the data safety and monitoring boards (DSMBs) for Lilly, AstraZeneca, Merck, Gilead, Novartis, Icosavax, Sanofi, Union Chimique Belge (UCB), Amgen, Biogen, BMS, Pulmocide, Alkermes, and Diurnal; is the nonprofit chairman of the board (unpaid) of the Frontier Science Foundation; and has stock/stock options in GSK, Clover, Athira, Doctor Evidence, DataVant, Spencer Health Solutions, and Adaptic Health. Dr Mavromatis reports grants from the NHLBI; grants from NHLBI (Cardiovascular Inflammation Reduction Trial and GMCSF in PAD-3 trial [Granulocyte-Macrophage Stimulating Factor (GM-CSF) in Peripheral Arterial Disease (GPAD-3)]); grants from CSL Behring, St Jude’s Medical, Medtronic, DalCor Pharmaceuticals, AstraZeneca, Novartis, and Regeneron; and is a member of the American College of Cardiology and the Society of Cardiovascular Angiography and Interventions. Dr Manjunath reports grants from NHLBI during the conduct of the study. Dr Stone reports grants from NHLBI during the conduct of the study; has received speaker honoraria from Pulnovo and Infraredx; has served as a consultant to Valfix, TherOx, Robocath, HeartFlow, Ablative Solutions, Vectorious, Miracor, Neovasc, Abiomed, Ancora, Elucid Bio, Occlutech, CorFlow, Apollo Therapeutics, Impulse Dynamics, Vascular Dynamics, Shockwave, V-Wave, Cardiomech, Gore, and Amgen; 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 daughter is an employee at Medtronic. Dr Stone’s employer, Mount Sinai Hospital, receives research support from Abbott, Bioventrix, Cardiovascular Systems, Inc, Phillips, Biosense-Webster, Shockwave, Vascular Dynamics, and V-Wave. Dr Mancini reports grants from NHLBI, during the conduct of the study; grants and personal fees from Amgen, Sanofi, Boehringer Ingelheim, AstraZeneca, Bayer, Janssen, and Novo Nordisk; grants from Novartis; and grants and personal fees from HLS Therapeutics, outside the submitted work. Dr Boden reports grants from NHLBI, during the conduct of the study; grants from Abbvie, Amarin, and Amgen; and personal fees from Amgen, the Cleveland Clinic Clinical Coordinating Center, and Janssen, outside the submitted work. Dr Newman reports grants from NHLBI, during the conduct of the study. Dr Reynolds reports grants from NHLBI, during the conduct of the study, and receives 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). Dr Hochman is a primary investigator for the ISCHEMIA trial (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) 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 Corporation, Omron Healthcare, Inc, Sunovion Pharmaceuticals, Inc, Espero BioPharma, and Amgen, Inc, and financial donations from Arbor Pharmaceuticals LLC and AstraZeneca Pharmaceuticals LP. Dr Hochman is also a primary investigator for the ISCHEMIA-EXTEND trial (The International Study of Comparative Health Effectiveness With Medical and Invasive Approaches [ISCHEMIA] Extended Follow-Up). Dr Maron reports grants from NHLBI, during the conduct of the study. The other authors report no conflicts.