Marc P Bonaca1, Robert F Storey2, Pierre Theroux3, P Gabriel Steg4, Deepak L Bhatt5, Marc C Cohen6, KyungAh Im5, Sabina A Murphy5, Giulia Magnani7, Ton Oude Ophuis8, Mikhail Rudah9, Alexander Parkhomenko10, Daniel Isaza11, Gabriel Kamensky12, Assen Goudev13, Gilles Montalescot14, Eva C Jensen15, Per Johanson15, Eugene Braunwald5, Marc S Sabatine5. 1. TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts. Electronic address: mbonaca@partners.org. 2. Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, United Kingdom. 3. University of Montreal, Montreal, Quebec, Canada. 4. Département de Cardiologie Hôpital Bichat, Assistance Publique - Hôpitaux de Paris, Paris, France. 5. TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts. 6. Newark Beth Israel Medical Center, Rutgers Medical School, Newark, New Jersey. 7. University Hospital Zurich, Zurich, Switzerland. 8. CWZ Hospital, Nijmegen, the Netherlands. 9. Cardiology Research Center, Moscow, Russian Federation. 10. Institute of Cardiology, Kiev, Ukraine. 11. Fundación Cardioinfantil, Bogotá, Colombia. 12. Department of Noninvasive Cardiovascular Diagnostics, Vth Internal Clinic, University Hospital Bratislava, Bratislava, Slovakia. 13. Medical University of Sofia, Queen Ioanna University Hospital, Sofia, Bulgaria. 14. Sorbonne Université Paris 6, ACTION Study Group, INSERM-UMRS 1166, Institut de Cardiologie, Pitié-Salpêtrière Hospital (AP-HP), Paris, France. 15. AstraZeneca, Mölndal, Sweden.
Abstract
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 UsingTicagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis In Myocardial Infarction) 54 trial randomized patients with prior MI (median 1.7 years prior) toticagrelor 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 UsingTicagrelor Compared to Placebo on a Background of Aspirin [PEGASUS]; NCT01225562).
RCT Entities:
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).
Authors: Fabrizio D'Ascenzo; Ovidio De Filippo; Edoardo Elia; Mattia Paolo Doronzo; Pierluigi Omedè; Antonio Montefusco; Mauro Pennone; Stefano Salizzoni; Federico Conrotto; Guglielmo Gallone; Filippo Angelini; Luca Franchin; Francesco Bruno; Massimo Boffini; Mario Gaudino; Mauro Rinaldi; Gaetano Maria De Ferrari Journal: Eur Heart J Qual Care Clin Outcomes Date: 2021-09-16
Authors: Eva Lesén; Christopher Hewitt; Evangelos Giannitsis; Jonatan Hedberg; Tomas Jernberg; Dimitra Lambrelli; Aldo P Maggioni; Jason C Simeone; Albert Ariza-Solé; Robert F Storey; Jurrien Ten Berg; Marc Bonaca Journal: Clin Cardiol Date: 2021-08-08 Impact factor: 2.882