Influence of body weight and body mass index on the chronic pharmacokinetic and pharmacodynamic responses to clinically available doses of ticagrelor in patients with chronic coronary syndromes.

Ticagrelor has multiple indications, including for some patients with chronic coronary syndromes (CCS) at high risk of ischaemic events. Body mass can potentially affect pharmacodynamics (PD) and pharmacokinetics (PK). We investigated the influence of body mass (range 53-172 kg, 20.8-46.9 kg/m

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Declaration of Competing Interest W.A.E. Parker reports institutional research grants and personal fees from AstraZeneca. D.J. Angiolillo has received consulting fees or honoraria from Abbott, 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 and St Jude Medical; and his institution has received research grants from Amgen, AstraZeneca, Bayer, Biosensors, CeloNova, CSL Behring, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Idorsia, Janssen, Matsutani Chemical Industry Co, Merck, Novartis, Osprey Medical, Renal Guard Solutions, and the Scott R. MacKenzie Foundation. F. Rollini declares that he has received honoraria from Chiesi. F. Franchi. declares that he has received consulting fees or honoraria from AstraZeneca, Bayer and Sanofi. He also declares that has received research grants from PLx Pharma and Scott R. MacKenzie Foundation. M.P. Bonaca is the Executive Director of CPC, a non-profit academic research organization affiliated with the University of Colorado, that receives research grant/consulting funding from: Abbott, Agios, Alexion Pharma, Alnylam, Amgen, Angionetics, ARCA Biopharma, Array, AstraZeneca, Atentiv, Audentes, Bayer, Better Therapeutics, Brigham and Women's Hospital, Bristol-Myers Squibb, Cardiol Therapeutics, CellResearch, Cook Medical, Cook, CSL Behring, Eidos Therapeutics, EP Trading Co, Esperion Therapeutics, EverlyWell, Faraday, Fortress Biotech, HDL Therapeutics, Heartflow, Hummingbird Bioscience, Insmed, Janssen, Kowa Research, Lexicon, Merck, Medtronic, Moderna, Novate Medical, NovoNordisk, Pfizer, PhaseBio, PPD Development, Prairie Education and Research, Prothena Ciosciences, Regeneron, Regio Biosciences, Sanifit Therapeutics, Sanofi, Smith and Nephew, Stealth BioTherapeutics, University of Colorado, Worldwide Clinical Trials, Wraser, Yale Cardiovascular Research Group. Dr. Bonaca also reports stock in Medtronic and Pfizer and consulting fees from Audentes. D.L. Bhatt discloses the following relationships - Advisory Board: AngioWave, Bayer, Boehringer Ingelheim, Cardax, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, Janssen, Level Ex, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, Regado Biosciences, Stasys; Board of Directors: AngioWave (stock options), Boston VA Research Institute, DRS.LINQ (stock options), Society of Cardiovascular Patient Care, TobeSoft; Chair: Inaugural Chair, American Heart Association Quality Oversight Committee; Data Monitoring Committees: Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Boston Scientific (Chair, PEITHO trial), Cleveland Clinic (including for the ExCEED trial, funded by Edwards), Contego Medical (Chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo; for the ABILITY-DM trial, funded by Concept Medical), Novartis, Population Health Research Institute; Rutgers University (for the NIH-funded MINT Trial); Honoraria: American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Chair, ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol-Myers Squibb clopidogrel litigation), 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), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), Cowen and Company, 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), Journal of the American College of Cardiology (Guest Editor; Associate Editor), K2P (Co-Chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Oakstone CME (Course Director, Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co‑leader, funded by Bayer), Slack Publications (Chief Medical Editor, Cardiology Today's Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), WebMD (CME steering committees), Wiley (steering committee); Other: Clinical Cardiology (Deputy Editor), NCDR-ACTION Registry Steering Committee (Chair), VA CART Research and Publications Committee (Chair); Research Funding: Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, 89Bio; Royalties: Elsevier (Editor, Braunwald's Heart Disease); Site Co-Investigator: Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St. Jude Medical (now Abbott), Philips, Svelte, Vascular Solutions; Trustee: American College of Cardiology; Unfunded Research: FlowCo, Takeda. P.G.Steg reports receiving research grants from Bayer, Merck, Sanofi, Servier and receiving consulting fees or honoraria from Amarin, Amgen, AstraZeneca, Bayer, Bristol-Myers-Squibb, Janssen, Kowa, Idorsia, Lexicon, Merck, Novartis, Novo-Nordisk, PhaseBio, Pfizer, Regeneron, Sanofi, Servier. M. R. Thomas reports institutional research grants from Novartis, Sanofi, Rigel and Acticor Pharmaceuticals and consultancy fees from Cytosorbents. M. S. Sabatine reports research grant support through Brigham and Women's Hospital from: Abbott; Amgen; Anthos Therapeutics; AstraZeneca; Bayer; Daiichi-Sankyo; Eisai; Intarcia; Ionis; Medicines Company; MedImmune; Merck; Novartis; Pfizer; Quark Pharmaceuticals. Consulting for: Althera; Amgen; Anthos Therapeutics; AstraZeneca; Beren Therapeutics; Bristol-Myers Squibb; DalCor; Dr. Reddy's Laboratories; Fibrogen; Intarcia; Merck; Moderna; Novo Nordisk; and Silence Therapeutics. R.F. Storey reports institutional research grants and personal fees from AstraZeneca, Cytosorbents, GlyCardial Diagnostics and Thromboserin; and personal fees from Alnylam, Bayer, Bristol Myers Squibb/Pfizer, Chiesi, CSL Behring, Hengrui, Idorsia, Novartis, PhaseBio, Portola, and Sanofi Aventis. The other authors have no relevant disclosures.