Author + information
- Received April 23, 2017
- Revision received July 12, 2017
- Accepted July 14, 2017
- Published online September 4, 2017.
- Marc P. Bonaca, MD, MPHa,∗ (, )
- Robert F. Storey, MDb,
- Pierre Theroux, MDc,
- P. Gabriel Steg, MDd,
- Deepak L. Bhatt, MD, MPHa,
- Marc C. Cohen, MDe,
- KyungAh Im, PhDa,
- Sabina A. Murphy, MPHa,
- Giulia Magnani, MDf,
- Ton Oude Ophuis, MDg,
- Mikhail Rudah, MDh,
- Alexander Parkhomenko, MDi,
- Daniel Isaza, MDj,
- Gabriel Kamensky, MDk,
- Assen Goudev, MD, PhDl,
- Gilles Montalescot, MD, PhDm,
- Eva C. Jensen, MD, PhDn,
- Per Johanson, MDn,
- Eugene Braunwald, MDa and
- Marc S. Sabatine, MD, MPHa
- aTIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts
- bDepartment of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, United Kingdom
- cUniversity of Montreal, Montreal, Quebec, Canada
- dDépartement de Cardiologie Hôpital Bichat, Assistance Publique - Hôpitaux de Paris, Paris, France
- eNewark Beth Israel Medical Center, Rutgers Medical School, Newark, New Jersey
- fUniversity Hospital Zurich, Zurich, Switzerland
- gCWZ Hospital, Nijmegen, the Netherlands
- hCardiology Research Center, Moscow, Russian Federation
- iInstitute of Cardiology, Kiev, Ukraine
- jFundación Cardioinfantil, Bogotá, Colombia
- kDepartment of Noninvasive Cardiovascular Diagnostics, Vth Internal Clinic, University Hospital Bratislava, Bratislava, Slovakia
- lMedical University of Sofia, Queen Ioanna University Hospital, Sofia, Bulgaria
- mSorbonne Université Paris 6, ACTION Study Group, INSERM-UMRS 1166, Institut de Cardiologie, Pitié-Salpêtrière Hospital (AP-HP), Paris, France
- nAstraZeneca, Mölndal, Sweden
- ↵∗Address for correspondence:
Dr. Marc P. Bonaca, TIMI Study Group, Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis Street, Boston, Massachusetts 02115.
Background Ticagrelor reduces ischemic risk in patients with prior myocardial infarction (MI). It remains unclear whether ischemic risk and the benefits of prolonged P2Y12 inhibition in this population remain consistent over time.
Objectives The study sought to investigate the pattern of ischemic risk over time and whether the efficacy and safety of ticagrelor were similar early and late after randomization.
Methods The PEGASUS-TIMI (Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin–Thrombolysis In Myocardial Infarction) 54 trial randomized patients with prior MI (median 1.7 years prior) to ticagrelor 90 mg, ticagrelor 60 mg, or placebo on a background of aspirin. The rates of cardiovascular (CV) death, MI, and stroke as well as TIMI major bleeding were analyzed at yearly landmarks (years 1, 2, and 3).
Results A total of 21,162 patients were randomized and followed for 33 months (median), with 28% of patients ≥5 years from MI at trial conclusion. The risk of CV death, MI, or stroke in the placebo arm remained roughly constant over the trial at an ∼3% annualized rate. The benefit of ticagrelor 60 mg was consistent at each subsequent landmark (year 1 hazard ratio [HR]: 0.82; 95% confidence interval [CI]: 0.67 to 0.99; year 2 HR: 0.90; 95% CI: 0.74 to 1.11; and year 3 HR: 0.79; 95% CI: 0.62 to 1.00). TIMI major bleeding was increased with ticagrelor 60 mg at each landmark, but with the greatest hazard in the first year (year 1 HR: 3.22; year 2 HR: 2.07; year 3 HR: 1.65).
Conclusions Patients with a history of MI remain at persistent high risk for CVD, MI, and stroke as late as 5 years after MI. The efficacy of low-dose ticagrelor is consistent over time with a trend toward less excess bleeding. (Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin [PEGASUS]; NCT01225562)
This study was supported by a grant to Brigham and Women’s Hospital from AstraZeneca. The TIMI Study Group has received significant research grant support from Accumetrics, Amgen, AstraZeneca, Beckman Coulter, Bristol-Myers Squibb, CV Therapeutics, Daiichi-Sankyo Co. Ltd., Eli Lilly and Co., GlaxoSmithKline, Integrated Therapeutics, MedImmune, Merck and Co., Nanosphere, Novartis Pharmaceuticals, Nuvelo, Ortho-Clinical Diagnostics, Pfizer, Roche Diagnostics, Sanofi, Sanofi-Synthélabo, Siemens Medical Solutions, and Singulex. Dr. Bonaca has served as a consultant for AstraZeneca, Merck, Aralez, and Bayer; and has received grant support from AstraZeneca. Dr. Storey has received research grants, consultancy fees, and honoraria from AstraZeneca; research grants and consultancy fees from PlaqueTec; and consultancy fees from Actelion, Avacta, Bayer, Bristol-Myers Squibb/Pfizer alliance, Novartis, The Medicines Company, and ThermoFisher Scientific. Dr. Steg has received significant research grants from Merck, Sanofi, and Servier; other personal fees and nonfinancial support from AstraZeneca, Sanofi, and Servier; and has served as a speaker or consultant (including steering committee, data monitoring committee, and clinical endpoints committee memberships) from Amarin, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, CSL-Behring, Daiichi-Sankyo, Lilly, Merck, Janssen, Novartis, Medtronic, Pfizer, The Medicines Company, GlaxoSmithKline, and Regeneron. Dr. Bhatt has served on the advisory board for Cardax, Elsevier Practice Update Cardiology, Medscape Cardiology, and Regado Biosciences; has served on the board of directors of the Boston VA Research Institute and Society of Cardiovascular Patient Care; has served as the chair of American Heart Association Quality Oversight Committee; has served on the data monitoring committees of the Cleveland Clinic, Duke Clinical Research Institute, Harvard Clinical Research Institute, Mayo Clinic, Population Health Research Institute; has received honoraria from the American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org), Belvoir Publications (Editor-in-Chief, Harvard Heart Letter), Duke Clinical Research Institute (clinical trial steering committees), Harvard Clinical Research Institute (clinical trial steering committee), HMP Communications (Editor-in-Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (guest editor, associate editor), Population Health Research Institute (clinical trial steering committee), Slack Publications (chief medical editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (secretary/treasurer), and WebMD (CME steering committees); has served as the deputy editor for Clinical Cardiology; has served as the chair of the NCDR-ACTION Registry Steering Committee and VA CART Research and Publications Committee; has received research funding from Amarin, Amgen, AstraZeneca, Bristol-Myers Squibb, Chiesi, Eisai, Ethicon, Forest Laboratories, Ironwood, Ischemix, Lilly, Medtronic, Pfizer, Roche, Sanofi, and The Medicines Company; has received royalties from Elsevier (Editor, Cardiovascular Intervention: A Companion to Braunwald’s Heart Disease); has served as a site co-investigator for Biotronik, Boston Scientific, and St. Jude Medical; has served as a trustee of American College of Cardiology; and has performed unfunded research for FlowCo, PLx Pharma, and Takeda. Dr. Cohen has received grants and personal fees from AstraZeneca; personal fees from Merck, Janssen, Maquet, malpractice attorneys, Merck, Bristol-Myers Squibb/Pfizer, Boehringer Ingelheim, and Eli Lilly; and has received grant support from Janssen and Edwards Lifesciences. Dr. Ophuis has received speaker fees from AstraZeneca and Amgen; and has received grant support from Medtronic and Abbott. Dr. Parkhomenko has received research grant support and lecture fees from AZ Company. Dr. Kamensky has participated in the PEGASUS-TIMI 54 trial supported by AstraZeneca. Dr. Goudev has received speaker honoraria from and served on the advisory board for AstraZeneca. Dr. Montalescot has received institutional research grant support and consulting/lecture fees from Actelion, Amgen, AstraZeneca, Bayer, Beth Israel Deaconess Medical, Boehringer Ingelheim, Brigham Women’s Hospital, Bristol-Myers Squibb, Cardiovascular Research Foundation, CCC, Celladon, CME Resources, Daiichi-Sankyo, Eli Lilly, Elsevier, Europa, Fédération Française de Cardiologie, ICAN, INSERM, Lead-Up, Medtronic, Menarini, Merck Sharp & Dohme, Pfizer, Sanofi, Servier, TIMI Study Group, and WebMD. Drs. Jensen and Johanson are employees of AstraZeneca. Dr. Braunwald has received institutional grant support from AstraZeneca. Dr. Sabatine has received research grant support through Brigham and Women’s Hospital from Abbott Laboratories, Amgen, AstraZeneca, Critical Diagnostics, Daiichi-Sankyo, Eisai, Genzyme, Gilead, GlaxoSmithKline, Intarcia, Janssen Research Development, MedImmune, Merck, Novartis, Poxel, Pfizer, Roche Diagnostics, and Takeda; and has served as a consultant for Alnylam, Amgen, AstraZeneca, Cubist, CVS Caremark, Esperion, Intarcia, Ionis, The Medicines Company, MedImmune, Merck, MyoKardia, and Zeus Scientific. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received April 23, 2017.
- Revision received July 12, 2017.
- Accepted July 14, 2017.
- 2017 American College of Cardiology Foundation
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