Improving the Design of Future PCI Trials for Stable Coronary Artery Disease: JACC State-of-the-Art Review

Guillaume Marquis-Gravel; David J. Moliterno; Darrel P. Francis; Peter Jüni; Yves D. Rosenberg; Bimmer E. Claessen; Robert J. Mentz; Roxana Mehran; Donald E. Cutlip; Cynthia Chauhan; Susan Quella; Faiez Zannad; Shaun G. Goodman

doi:10.1016/j.jacc.2020.05.060

Improving the Design of Future PCI Trials for Stable Coronary Artery Disease: JACC State-of-the-Art Review

Guillaume Marquis-Gravel, David J. Moliterno, Darrel P. Francis, Peter Jüni, Yves D. Rosenberg, Bimmer E. Claessen, Robert J. Mentz, Roxana Mehran, Donald E. Cutlip, Cynthia Chauhan, Susan Quella, Faiez Zannad, Shaun G. Goodman

Research output: Contribution to journal › Review article › peer-review

11 Scopus citations

Abstract

The role of percutaneous coronary interventions in addition to medical therapy for patients with stable coronary artery disease continues to be debated in routine clinical practice, despite more than 2 decades of randomized controlled trials. The residual uncertainty arises from particular challenges facing revascularization trials. Which endpoint do doctors care about, and which do patients care about? Which participants should be enrolled? What background medical therapy should we use? When is placebo control relevant? In this paper, we discuss how these questions can be approached and examine the merits and disadvantages of possible options. Engaging multiple stakeholders, including patients, researchers, regulators, and funders, to ensure the design elements are methodologically valid and clinically meaningful should be an aspirational goal in the development of future trials.

Original language	English
Pages (from-to)	435-450
Number of pages	16
Journal	Journal of the American College of Cardiology
Volume	76
Issue number	4
DOIs	https://doi.org/10.1016/j.jacc.2020.05.060
State	Published - Jul 28 2020

Bibliographical note

Publisher Copyright:
© 2020 American College of Cardiology Foundation

Funding

The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services. Dr. Marquis-Gravel has received speaker fees and honoraria from Novartis and Servier unrelated to this paper; and has received a grant from the Canadian Institute of Health Research, Ottawa, Ontario, Canada. Dr. Moliterno has received a research grant from AstraZeneca. Dr. Jüni serves as an unpaid member of the Steering Group for trials funded by Abbott Vascular, AstraZeneca, Biotronik, Biosensors, St. Jude Medical, and The Medicines Company; has received research grants to the institution from AstraZeneca, Biotronik, Biosensors International, Eli Lilly, and The Medicines Company; and has received honoraria to the institution for participation in Advisory Boards and/or consulting from Amgen, Ava, and Fresenius, but has not received personal payments from any pharmaceutical company or device manufacturer. Dr. Mentz has received research support from the National Institutes of Health (U01HL125511-01A1 and R01AG045551-01A1), Akros, Amgen, AstraZeneca, Bayer, GlaxoSmithKline, Gilead, InnoLife, Luitpold/American Regent, Medtronic, Merck, Novartis, and Sanofi; has received honoraria from Abbott, Amgen, AstraZeneca, Bayer, Boston Scientific, Janssen, Luitpold Pharmaceuticals, Medtronic, Merck, Novartis, Sanofi, and Vifor; and has served on an Advisory Board for Amgen, AstraZeneca, Luitpold, Merck, Novartis, and Boehringer Ingelheim. Dr. Mehran has received personal fees from Abbott Vascular Laboratories, Boston Scientific, Janssen, Watermark Research Funding, American College of Cardiology, Journal of the American Medical Association, Medscape/Web MD, Medtelligence, Bayer, Roivant Sciences, Siemens Medical Solutions, and Sanofi; has received grants from AstraZeneca, Bayer, Beth Israel Deaconess, Bristol-Myers Squibb, Cardiovascular European Research Center, Chiesi, Concept Medical, CSL Behring, DSI, Medtronic, Novartis Pharmaceuticals, OrbusNeich, and Abbott Vascular, outside the submitted work; has served on the Advisory Board for Phillips/Volcano/Spectranetics (funding paid to institution); has received consultant fees to her spouse from Abiomed and The Medicines Company; has performed unpaid consulting for Idorsia Pharmaceuticals Ltd., and Regeneron Pharmaceuticals; and has received Data Safety Monitoring Board membership fees paid to the institution by Watermark Research Partners. Dr. Cutlip has received salary support from the Baim Institute for Clinical Research; and has performed consulting for Celonova. Dr. Zannad has received steering committee fees from Janssen, Novartis, Boston Scientific, CVRx, Boehringer, AstraZeneca, Cellprothera, and Bayer; has received consultant fees from Amgen, AstraZeneca, Vifor Fresenius, Cardior, Cereno Pharmaceutical, Applied Therapeutics, Merck, Bayer, and Cellprothera; and is founder of CardioVascular Clinical Trialists (CVCT) and Cardiorenal. Dr. Goodman has received research grant support (e.g., Steering Committee or Data Monitoring Committee) and/or speaker/consulting honoraria (e.g., Advisory Boards) from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, CSL Behring, Daiichi-Sankyo/American Regent, Eli Lilly, Esperion, Fenix Group International, Ferring Pharmaceuticals, GlaxoSmithKline, HLS Therapeutics, Janssen/Johnson & Johnson, Luitpold Pharmaceuticals, Matrizyme, Merck, Novartis, Novo Nordisk A/C, Pfizer, Regeneron, Sanofi, Servier, and Tenax Therapeutics; and received salary support from the Heart and Stroke Foundation of Ontario/University of Toronto (Polo), the Canadian Heart Research Centre, MD Primer, Canadian VIGOUR Centre, Duke Clinical Research Institute, New York University Clinical Coordinating Centre, and PERFUSE. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Harsh Golwala, MD, served as Guest Associate Editor for this paper. Deepak L. Bhatt, MD, MPH, served as Guest Editor-in-Chief for this paper. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services. Dr. Marquis-Gravel has received speaker fees and honoraria from Novartis and Servier unrelated to this paper; and has received a grant from the Canadian Institute of Health Research, Ottawa, Ontario, Canada. Dr. Moliterno has received a research grant from AstraZeneca. Dr. Jüni serves as an unpaid member of the Steering Group for trials funded by Abbott Vascular, AstraZeneca, Biotronik, Biosensors, St. Jude Medical, and The Medicines Company; has received research grants to the institution from AstraZeneca, Biotronik, Biosensors International, Eli Lilly, and The Medicines Company; and has received honoraria to the institution for participation in Advisory Boards and/or consulting from Amgen, Ava, and Fresenius, but has not received personal payments from any pharmaceutical company or device manufacturer. Dr. Mentz has received research support from the National Institutes of Health (U01HL125511-01A1 and R01AG045551-01A1), Akros, Amgen, AstraZeneca, Bayer, GlaxoSmithKline, Gilead, InnoLife, Luitpold/American Regent, Medtronic, Merck, Novartis, and Sanofi; has received honoraria from Abbott, Amgen, AstraZeneca, Bayer, Boston Scientific, Janssen, Luitpold Pharmaceuticals, Medtronic, Merck, Novartis, Sanofi, and Vifor; and has served on an Advisory Board for Amgen, AstraZeneca, Luitpold, Merck, Novartis, and Boehringer Ingelheim. Dr. Mehran has received personal fees from Abbott Vascular Laboratories, Boston Scientific, Janssen, Watermark Research Funding, American College of Cardiology, Journal of the American Medical Association, Medscape/Web MD, Medtelligence, Bayer, Roivant Sciences, Siemens Medical Solutions, and Sanofi; has received grants from AstraZeneca, Bayer, Beth Israel Deaconess, Bristol-Myers Squibb, Cardiovascular European Research Center, Chiesi, Concept Medical, CSL Behring, DSI, Medtronic, Novartis Pharmaceuticals, OrbusNeich, and Abbott Vascular, outside the submitted work; has served on the Advisory Board for Phillips/Volcano/Spectranetics (funding paid to institution); has received consultant fees to her spouse from Abiomed and The Medicines Company; has performed unpaid consulting for Idorsia Pharmaceuticals Ltd., and Regeneron Pharmaceuticals; and has received Data Safety Monitoring Board membership fees paid to the institution by Watermark Research Partners. Dr. Cutlip has received salary support from the Baim Institute for Clinical Research; and has performed consulting for Celonova. Dr. Zannad has received steering committee fees from Janssen, Novartis, Boston Scientific, CVRx, Boehringer, AstraZeneca, Cellprothera, and Bayer; has received consultant fees from Amgen, AstraZeneca, Vifor Fresenius, Cardior, Cereno Pharmaceutical, Applied Therapeutics, Merck, Bayer, and Cellprothera; and is founder of CardioVascular Clinical Trialists (CVCT) and Cardiorenal. Dr. Goodman has received research grant support (e.g., Steering Committee or Data Monitoring Committee) and/or speaker/consulting honoraria (e.g., Advisory Boards) from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, CSL Behring, Daiichi-Sankyo/American Regent, Eli Lilly, Esperion, Fenix Group International, Ferring Pharmaceuticals, GlaxoSmithKline, HLS Therapeutics, Janssen/Johnson & Johnson, Luitpold Pharmaceuticals, Matrizyme, Merck, Novartis, Novo Nordisk A/C, Pfizer, Regeneron, Sanofi, Servier, and Tenax Therapeutics; and received salary support from the Heart and Stroke Foundation of Ontario/University of Toronto (Polo), the Canadian Heart Research Centre, MD Primer, Canadian VIGOUR Centre, Duke Clinical Research Institute, New York University Clinical Coordinating Centre, and PERFUSE. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Harsh Golwala, MD, served as Guest Associate Editor for this paper. Deepak L. Bhatt, MD, MPH, served as Guest Editor-in-Chief for this paper.

Funders	Funder number
Applied Therapeutics
Baim Institute for Clinical Research
The Canadian Heart Research Centre
Cardiovascular European Research Center
Cereno Pharmaceutical
Concept Medical
Duke Clinical Research Institute, New York University
Heart and Stroke Foundation of Ontario/University
Janssen/Johnson & Johnson
PERFUSE Research Institute
Vifor Pharma Management
National Institutes of Health (NIH)
U.S. Department of Health and Human Services
National Heart, Lung, and Blood Institute (NHLBI)	U01HL125511
Abbott Laboratories
AMGen
Bristol-Myers Squibb
Eli Lilly and Company	R01AG045551-01A1
AstraZeneca
Bayer
GlaxoSmithKline
Merck
Novartis
Sanofi
Medtronic
Gilead Sciences
St. Jude Medical Center
Chiesi Farmaceutici S.p.A.
Novartis Pharmaceuticals Corporation
CSL Behring GmbH
Boehringer-Ingelheim
Boston Scientific Neuromodulation Corporation
Janssen Pharmaceuticals
American Medical Association
Abbott Vascular
Medicines Company
Luitpold Pharmaceuticals, Inc.
Tenax Therapeutics
Canadian Institutes of Health Research
Ferring Pharmaceuticals
Biotronik Incorporated
Biosensors International Group
Defence Science Institute
Servier Institute
Idorsia Pharmaceuticals Ltd.
HLS Therapeutics
OrbusNeich

Keywords

coronary artery disease
methods
percutaneous coronary intervention
randomized controlled trials

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

Access to Document

10.1016/j.jacc.2020.05.060

Cite this

Marquis-Gravel, G., Moliterno, D. J., Francis, D. P., Jüni, P., Rosenberg, Y. D., Claessen, B. E., Mentz, R. J., Mehran, R., Cutlip, D. E., Chauhan, C., Quella, S., Zannad, F., & Goodman, S. G. (2020). Improving the Design of Future PCI Trials for Stable Coronary Artery Disease: JACC State-of-the-Art Review. Journal of the American College of Cardiology, 76(4), 435-450. https://doi.org/10.1016/j.jacc.2020.05.060

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title = "Improving the Design of Future PCI Trials for Stable Coronary Artery Disease: JACC State-of-the-Art Review",

abstract = "The role of percutaneous coronary interventions in addition to medical therapy for patients with stable coronary artery disease continues to be debated in routine clinical practice, despite more than 2 decades of randomized controlled trials. The residual uncertainty arises from particular challenges facing revascularization trials. Which endpoint do doctors care about, and which do patients care about? Which participants should be enrolled? What background medical therapy should we use? When is placebo control relevant? In this paper, we discuss how these questions can be approached and examine the merits and disadvantages of possible options. Engaging multiple stakeholders, including patients, researchers, regulators, and funders, to ensure the design elements are methodologically valid and clinically meaningful should be an aspirational goal in the development of future trials.",

keywords = "coronary artery disease, methods, percutaneous coronary intervention, randomized controlled trials",

author = "Guillaume Marquis-Gravel and Moliterno, \{David J.\} and Francis, \{Darrel P.\} and Peter J{\"u}ni and Rosenberg, \{Yves D.\} and Claessen, \{Bimmer E.\} and Mentz, \{Robert J.\} and Roxana Mehran and Cutlip, \{Donald E.\} and Cynthia Chauhan and Susan Quella and Faiez Zannad and Goodman, \{Shaun G.\}",

note = "Publisher Copyright: {\textcopyright} 2020 American College of Cardiology Foundation",

year = "2020",

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day = "28",

doi = "10.1016/j.jacc.2020.05.060",

language = "English",

volume = "76",

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Marquis-Gravel, G, Moliterno, DJ, Francis, DP, Jüni, P, Rosenberg, YD, Claessen, BE, Mentz, RJ, Mehran, R, Cutlip, DE, Chauhan, C, Quella, S, Zannad, F & Goodman, SG 2020, 'Improving the Design of Future PCI Trials for Stable Coronary Artery Disease: JACC State-of-the-Art Review', Journal of the American College of Cardiology, vol. 76, no. 4, pp. 435-450. https://doi.org/10.1016/j.jacc.2020.05.060

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AU - Cutlip, Donald E.

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Improving the Design of Future PCI Trials for Stable Coronary Artery Disease: JACC State-of-the-Art Review

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Bibliographical note

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Keywords

ASJC Scopus subject areas

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