Sameer Bansilal1, Marc P Bonaca2, Jan H Cornel3, Robert F Storey4, Deepak L Bhatt2, Ph Gabriel Steg5, Kyungah Im2, Sabina A Murphy2, Dominick J Angiolillo6, Robert G Kiss7, Alexander N Parkhomenko8, Jose Lopez-Sendon9, Daniel Isaza10, Assen Goudev11, Frederic Kontny12, Peter Held13, Eva C Jensen13, Eugene Braunwald2, Marc S Sabatine14, A J Oude Ophuis15. 1. Zena and Michael Weiner Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York. 2. TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. 3. Department of Cardiology, Noordwest Ziekenhuisgroep, Alkmaar and Dutch Network for Cardiovascular Research (WCN), the Netherlands. 4. Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, United Kingdom. 5. DHU (Département Hospitalo-Universitaire)-FIRE (Fibrosis, Inflammation, REmodelling), Hôpital Bichat, AP-HP (Assistance Publique-Hôpitaux de Paris), Université Paris-Diderot, Sorbonne-Paris Cité, and FACT (French Alliance for Cardiovascular clinical Trials), an F-CRIN network, INSERM U-1148, Paris, France; National Heart and Lung Institute, Institute of Cardiovascular Medicine and Science, Royal Brompton Hospital, Imperial College, London, United Kingdom. 6. Division of Cardiology, University of Florida College of Medicine, Jacksonville, Florida. 7. Department of Cardiology, Military Hospital, Budapest, Hungary. 8. Emergency Cardiology Department, Institute of Cardiology, Kiev, Ukraine. 9. Hospital Universitario La Paz, Madrid, Spain. 10. Fundacion Cardioinfantil, Instituto de Cardiología, Bogotá, Cundinamarca, Colombia. 11. Medical University Sofia, Queen Ioanna Hospital, Sofia, Bulgaria. 12. Department of Cardiology, Stavanger University Hospital, Stavanger, Norway; Drammen Heart Center, Drammen, Norway. 13. AstraZeneca Research and Development, Mölndal, Sweden. 14. TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. Electronic address: msabatine@partners.org. 15. Department of Cardiology, Noordwest Ziekenhuisgroep, Alkmaar and Dutch Network for Cardiovascular Research (WCN), the Netherlands; Department of Cardiology, CWZ Hospital, Nijmegen, the Netherland.
Abstract
BACKGROUND:Patients with prior myocardial infarction (MI) and multivessel coronary disease (MVD) are at high risk for recurrent coronary events. OBJECTIVES: The authors investigated the efficacy and safety of ticagrelor versus placebo in patients with MVD in the PEGASUS-TIMI 54 (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. METHODS:Patients with a history of MI 1 to 3 years before inclusion in the PEGASUS-TIMI 54 trial were stratified in a pre-specified analysis based on the presence of MVD. The effect of ticagrelor (60 mg and 90 mg) on the composite of cardiovascular death, MI, or stroke (major adverse cardiovascular events [MACE]), as well as the composite of coronary death, MI, or stent thrombosis (coronary events), and on TIMI major bleeding, intracranial hemorrhage (ICH), and fatal bleeding were evaluated over a median of 33 months. RESULTS: A total of 12,558 patients (59.4%) had MVD. In the placebo arm, compared with patients without MVD, those with MVD were at higher risk for MACE (9.37% vs. 8.57%, adjusted hazard ratio [HRadj]: 1.24; p = 0.026) and for coronary events (7.67% vs. 5.34%, HRadj: 1.49; p = 0.0005). In patients with MVD, ticagrelor reduced the risk of MACE (7.94% vs. 9.37%, HR: 0.82; p = 0.004) and coronary events (6.02% vs. 7.67%, HR: 0.76; p < 0.0001), including a 36% reduction in coronary death (HR: 0.64; 95% confidence interval: 0.48 to 0.85; p = 0.002). In this subgroup, ticagrelor increased the risk of TIMI major bleeding (2.52% vs. 1.08%, HR: 2.67; p < 0.0001), but not ICH or fatal bleeds. CONCLUSIONS: Patients with prior MI and MVD are at increased risk of MACE and coronary events, and experience substantial relative and absolute risk reductions in both outcomes with long-term ticagrelor treatment relative to those without MVD. Ticagrelor increases the risk of TIMI major bleeding, but not ICH or fatal bleeding. For patients with prior MI and MVD, ticagrelor is an effective option for long-term antiplatelet therapy. (Prevention of Cardiovascular Events [e.g., Death From Heart or Vascular Disease, Heart Attack, or Stroke] in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin [PEGASUS]; NCT01225562).
RCT Entities:
BACKGROUND:Patients with prior myocardial infarction (MI) and multivessel coronary disease (MVD) are at high risk for recurrent coronary events. OBJECTIVES: The authors investigated the efficacy and safety of ticagrelor versus placebo in patients with MVD in the PEGASUS-TIMI 54 (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. METHODS:Patients with a history of MI 1 to 3 years before inclusion in the PEGASUS-TIMI 54 trial were stratified in a pre-specified analysis based on the presence of MVD. The effect of ticagrelor (60 mg and 90 mg) on the composite of cardiovascular death, MI, or stroke (major adverse cardiovascular events [MACE]), as well as the composite of coronary death, MI, or stent thrombosis (coronary events), and on TIMI major bleeding, intracranial hemorrhage (ICH), and fatal bleeding were evaluated over a median of 33 months. RESULTS: A total of 12,558 patients (59.4%) had MVD. In the placebo arm, compared with patients without MVD, those with MVD were at higher risk for MACE (9.37% vs. 8.57%, adjusted hazard ratio [HRadj]: 1.24; p = 0.026) and for coronary events (7.67% vs. 5.34%, HRadj: 1.49; p = 0.0005). In patients with MVD, ticagrelor reduced the risk of MACE (7.94% vs. 9.37%, HR: 0.82; p = 0.004) and coronary events (6.02% vs. 7.67%, HR: 0.76; p < 0.0001), including a 36% reduction in coronary death (HR: 0.64; 95% confidence interval: 0.48 to 0.85; p = 0.002). In this subgroup, ticagrelor increased the risk of TIMI major bleeding (2.52% vs. 1.08%, HR: 2.67; p < 0.0001), but not ICH or fatal bleeds. CONCLUSIONS:Patients with prior MI and MVD are at increased risk of MACE and coronary events, and experience substantial relative and absolute risk reductions in both outcomes with long-term ticagrelor treatment relative to those without MVD. Ticagrelor increases the risk of TIMI major bleeding, but not ICH or fatal bleeding. For patients with prior MI and MVD, ticagrelor is an effective option for long-term antiplatelet therapy. (Prevention of Cardiovascular Events [e.g., Death From Heart or Vascular Disease, Heart Attack, or Stroke] in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin [PEGASUS]; NCT01225562).
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