Author + information
- Received May 27, 2020
- Accepted June 26, 2020
- Published online September 14, 2020.
- Davide Capodanno, MD, PhDa,∗ (, )@DFCapodanno,
- Marie-Claude Morice, MDb@mc_morice,
- Dominick J. Angiolillo, MD, PhDc,
- Deepak L. Bhatt, MD, MPHd@DLBhattMD,
- Robert A. Byrne, MB BCh, PhDe,f@robebyrne,
- Roisin Colleran, MB BChe,g,
- Thomas Cuisset, MDh@CuissetDr,
- Donald Cutlip, MDi@DonaldCutlip,
- Pedro Eerdmans, MD, PhD, MScj,
- John Eikelboom, MDk,
- Andrew Farb, MDl,
- C. Michael Gibson, MDm,n@CMichaelGibson,
- John Gregson, BSc, MSc, PhDo,
- Michael Haude, MDp,
- Stefan K. James, MDq,
- Hyo-Soo Kim, MDr,
- Takeshi Kimura, MDs,
- Akihide Konishi, MD, PhDt,
- Martin B. Leon, MDu,v@MartyMleon,
- P.F. Adrian Magee, MDl@dmylotte,
- Yoshiaki Mitsutake, MDt,
- Darren Mylotte, MDw,
- Stuart J. Pocock, PhDo,
- Sunil V. Rao, MDx@SVRaoMD,
- Ernest Spitzer, MDy,z@ernest_spitzer,
- Norman Stockbridge, MD, PhDl,
- Marco Valgimigli, MD, PhDaa@vlgmrc,
- Olivier Varenne, MDbb,cc,
- Ute Windhovel, PhDb@Urphi,
- Mitchel W. Krucoff, MDx,dd@mwkrucoff,
- Philip Urban, MDee and
- Roxana Mehran, MDff@Drroxmehran
- aDivision of Cardiology, Azienda Ospedaliero Universitario “Policlinico G. Rodolico-San Marco”, University of Catania, Catania, Italy
- bCardiovascular European Research Center, Massy, France
- cDivision of Cardiology, University of Florida College of Medicine, Jacksonville, Florida
- dBrigham and Women’s Hospital Heart & Vascular Center, Harvard Medical School, Boston, Massachusetts
- eCardiovascular Research Institute Dublin, Mater Private Hospital, Dublin, Ireland
- fSchool of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland
- gDeutsches Herzzentrum München, Technische Universität München, Munich, Germany
- hDépartement de Cardiologie, Centre Hospitalier Universitaire Timone and Inserm, Inra, Centre de Recherche en Cardiovasculaire et Nutrition, Faculté de Médecine, Aix-Marseille Université, Marseille, France
- iCardiology Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
- jDEKRA Certification, Arnhem, the Netherlands
- kDepartment of Medicine, McMaster University, Hamilton, Ontario, Canada
- lU.S. Food and Drug Administration, Silver Spring, Maryland
- mHarvard Medical School, Boston, Massachusetts
- nBaim Institute for Clinical Research, Brookline, Massachusetts
- oLondon School of Hygiene and Tropical Medicine, London, United Kingdom
- pStädtische Kliniken Neuss, Lukaskrankenhaus, Neuss, Germany
- qDepartment of Medical Sciences and Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden
- rCardiovascular Center, Seoul National University Hospital, Seoul, Korea
- sDepartment of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
- tOffice of Medical Devices 1, Pharmaceuticals and Medical Devices Agency, Tokyo, Japan
- uColumbia University Medical Center, New York, New York
- vCardiovascular Research Foundation, New York, New York
- wUniversity Hospital and National University of Ireland, Galway, Ireland
- xDuke Clinical Research Institute, Durham, North Carolina
- yThoraxcenter, Erasmus University Medical Center, Rotterdam, the Netherlands
- zCardialysis, Clinical Trial Management and Core Laboratories, Rotterdam, the Netherlands
- aaDepartment of Cardiology, Inselspital, University of Bern, Bern, Switzerland
- bbService de Cardiologie, Hôpital Cochin, Assistance Publique – Hôpitaux de Paris, Paris, France
- ccUniversité Paris Descartes, Sorbonne Paris-Cité, Paris, France
- ddDuke University Medical Center, Durham, North Carolina
- eeLa Tour Hospital, Geneva, Switzerland
- ffIcahn School of Medicine at Mount Sinai, New York, New York
- ↵∗Address for correspondence:
Dr. Davide Capodanno, Division of Cardiology, A.O.U. “Policlinico G. Rodolico-San Marco,” University of Catania, via Santa Sofia 78, 95124 Catania, Italy.
• Investigating the balance of risk for thrombotic and bleeding events after PCI is especially relevant for HBR patients.
• The aim of this consensus-based document is to propose recommendations to guide the design of clinical trials of devices and drugs in HBR patients undergoing PCI.
• Consensus definitions promote consistency in trial design for the evaluation of novel technologies, iterations of existing devices, and antithrombotic strategies.
Investigating the balance of risk for thrombotic and bleeding events after percutaneous coronary intervention (PCI) is especially relevant for patients at high bleeding risk (HBR). The Academic Research Consortium for HBR recently proposed a consensus definition in an effort to standardize the patient population included in HBR trials. The aim of this consensus-based document, the second initiative from the Academic Research Consortium for HBR, is to propose recommendations to guide the design of clinical trials of devices and drugs in HBR patients undergoing PCI. The authors discuss the designs of trials in HBR patients undergoing PCI and various aspects of trial design specific to HBR patients, including target populations, intervention and control groups, primary and secondary outcomes, and timing of endpoint reporting.
Dr. Colleran has received financial compensation from the Cardiovascular European Research Center (CERC) for her contribution to manuscript preparation. In accordance with the Academic Research Consortium charter, none of the other participants received fees or honoraria for their participation in the meetings or their contributions to this document. Dr. Capodanno has received consulting fees or honoraria from Abbott Vascular, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi-Sankyo, and Pfizer. Dr. Morice is the chief executive officer of CERC, the contract research organization organizing the Academic Research Consortium for High Bleeding Risk initiative. Dr. Angiolillo has received consulting fees or honoraria from Abbott Vascular, Amgen, Aralez, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Bristol-Myers Squibb, Chiesi, Daiichi-Sankyo, Eli Lilly, Haemonetics, Janssen, Merck, PhaseBio, PLx Pharma, Pfizer, Sanofi, and The Medicines Company; has received payments for participation in review activities from CeloNova Biosciences and St. Jude Medical; and has received research grants to his institution from Abbott, Amgen, AstraZeneca, Bayer, Biosensors, CeloNova, CSL Behring, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Idorsia, Janssen, Matsutani Chemical Industry, Merck, Novartis, Osprey Medical, Renal Guard Solutions, and the Scott R. MacKenzie Foundation. Dr. Bhatt is an Advisory Board member for Cardax, Cereno Scientific, Elsevier Practice Update Cardiology, Medscape Cardiology, PhaseBio, PLX Pharma, and Regado Biosciences; is a member of the boards of directors of the Boston VA Research Institute, the Society of Cardiovascular Patient Care, and TobeSoft; is chair of the American Heart Association Quality Oversight Committee; is a member of data monitoring committees for the Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), the Cleveland Clinic (including for the ExCEED trial, funded by Edwards Lifesciences), the Duke Clinical Research Institute, the Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi-Sankyo), and the Population Health Research Institute; has received honoraria from the American College of Cardiology (Senior Associate Editor, Clinical Trials and News and ACC.org; vice chair, ACC Accreditation Committee), the 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), the 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), the Journal of the American College of Cardiology (Guest Editor, Associate Editor), Medtelligence/ReachMD (continuing medical education steering committees), the Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and U.S. national coleader, funded by Bayer), Slack Publications (Chief Medical Editor, Cardiology Today’s Intervention), the Society of Cardiovascular Patient Care (secretary/treasurer), and WebMD (continuing medical education steering committees); is Deputy Editor of Clinical Cardiology; is Chair of the NCDR-ACTION Registry Steering Committee and the VA CART Research and Publications Committee; has received research funding from Abbott Vascular, Afimmune, Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Cardax, Chiesi, CSL Behring, Eisai, Eli Lilly, Ethicon, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Idorsia, Ironwood, Ischemix, Lexicon, Medtronic, Pfizer, PhaseBio, PLx Pharma, Regeneron, Roche, Sanofi, Synaptic, and The Medicines Company; has received royalties from Elsevier (Editor, Cardiovascular Intervention: A Companion to Braunwald’s Heart Disease); is a site co-investigator for Biotronik, Boston Scientific, Cardiovascular Systems, St. Jude Medical (now Abbott), and Svelte; is a trustee of the American College of Cardiology; and has conducted unfunded research for FlowCo, Merck, Novo Nordisk, and Takeda. Dr. Byrne has received research funding to the institution of previous employment from CeloNova Biosciences. Dr. Cutlip has received consulting fees from CeloNova Biosciences; and has received academic salary support from the Baim Institute for Clinical Research. Dr. Eikelboom has received consulting fees and grant support from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, Eli Lilly, GlaxoSmithKline, Pfizer, Janssen, and Sanofi. Dr. Gibson is chief executive officer of the Baim Institute for Clinical Research; has received research grant funding from Angel Medical, Bayer, CSL Behring, Janssen Pharmaceuticals, Johnson & Johnson, and Portola Pharmaceuticals; has received consulting fees from Amarin Pharma, Amgen, Bayer, Boehringer Ingelheim, the Boston Clinical Research Institute, Boston Scientific, the Cardiovascular Research Foundation, CSL Behring, Chiesi, the Duke Clinical Research Institute, Eli Lilly, Gilead Sciences, Impact Bio, Janssen Pharmaceuticals, Johnson & Johnson, The Medicines Company, MedImmune, Medtelligence, Merck, Microport, Novo Nordisk, the PERT Consortium, Pharma Mar, Portola Pharmaceuticals, Sanofi, Somahlution, Vereseon, and Web MD; and has received royalties as a contributor from UpToDate in Cardiovascular Medicine. Dr. Gregson has received personal fees from Edwards Lifesciences, MvRX, Amarin, and BioSensors. Dr. Haude has received grant support from Biotronik, Orbus Neich, Abbott, Medtronic, and Cardiac Dimensions; has received lecture fees from Biotronik, Orbus Neich, Abbott, Medtronic, Eli Lilly, Philips/Volcano, and Cardiac Dimensions (proctor); and has received consultant fees from Biotronik, Orbus Neich, and Abbott. Dr. James has received institutional research grants from AstraZeneca, Bayer, Janssen, The Medicines Company, Abbott Vascular, and Boston Scientific; and has received honoraria from AstraZeneca, Bayer, and Medtronic. Dr. Kimura has received consulting fees or honoraria from Abbott Vascular Japan, Kowa, Kowa Pharmaceutical, Sanofi, Nippon Boehringer Ingelheim, and Bristol-Myers Squibb; and has received grant support from Otsuka Pharmaceutical, Daiichi-Sankyo, Mitsubishi Tanabe Pharma, Takeda Pharmaceutical, and Nippon Boehringer Ingelheim. Dr. Leon has received research grants from Abbott Vascular, Boston Scientific, Medtronic, Biosensors, and Sinomed; and has equity in Medinol. Dr. Mylotte has received speaker fees from Biosensors; and has received institutional research grants from Biosensors and Medtronic. Dr. Pocock has served on steering committees or data monitoring committees for trials sponsored by AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Idorsia, Janssen, Medtronic, Novartis, Novo Nordisk, and Vifor; and has received grant funding from AstraZeneca and Merck. Dr. Valgimigli has received personal fees from AstraZeneca, Alvimedica/CID, Abbott Vascular, Daiichi-Sankyo, Opsens, Bayer, CoreFLOW, Idorsia Pharmaceuticals, Universität Basel, Dept. Klinische Forschung, Vifor, Bristol-Myers Squibb, iVascular, and Medscape; and has received grants and personal fees from Terumo. Dr. Varenne has received consulting and research grants from Boston Scientific, Abbott Vascular, AstraZeneca, and Servier. Dr. Krucoff has received consulting and research grants from Abbott Vascular, Biosensors, Boston Scientific, Cook Medical, Medtronic, and OrbusNeich. Dr. Urban has received speaker and consulting honoraria as an individual from Biosensors-Europe, Sinomed, and Terumo; has participated in paid review activities (clinical endpoint committee, data and safety monitoring board) for Edwards Lifesciences, Terumo, and Abbott Vascular; and has served as a medical codirector at CERC. Dr. Mehran has received consulting fees to the institution from Abbott Laboratories and Spectranetics/Philips/Volcano; has received consulting fees from Boston Scientific, Cardiovascular Systems, Medscape, Siemens Medical Solutions, Regeneron Pharmaceuticals, Roivant Sciences, and Sanofi; is the spouse of a consultant for Abiomed and The Medicines Company; has received research funding to the institution from AstraZeneca, Bayer, Beth Israel Deaconess Hospital, Bristol-Myers Squibb, CSL Behring, Eli Lilly and Daiichi-Sankyo, Medtronic, Novartis Pharmaceuticals, and Orbus Neich; has received scientific Advisory Board fees from PLx Opco (dba PLx Pharma); has received scientific Advisory Board fees to the institution from Bristol-Myers Squibb; has received executive committee fees from Janssen Pharmaceuticals and Osprey Medical; has participated in speaking engagements for Abbott Laboratories; holds equity in Claret Medical and Elixir Medical; and has received data and safety monitoring board fees to the institution from Atermark Research Partners. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. This paper reflects the consensus views of the writing group and does not necessarily represent the practices, policies, requirements, or recommendations of the U.S. Food and Drug Administration or the Japanese Pharmaceuticals and Medical Devices Agency. Further, any use of the words “required,” “must,” or “should” in the document is not intended to indicate an FDA requirement. Judith S. Hochman, MD, served as Guest Associate Editor for this paper. P.K. Shah, MD, served as Guest Editor-in-Chief for this paper.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC author instructions page.
- Received May 27, 2020.
- Accepted June 26, 2020.
- 2020 American College of Cardiology Foundation
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