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Circulation. 2016 Sep 20;134(12):861-71. doi: 10.1161/CIRCULATIONAHA.116.024637. Epub 2016 Aug 30.

Prevention of Stroke with Ticagrelor in Patients with Prior Myocardial Infarction: Insights from 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).

Author information

  • 1From TIMI Study Group, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (M.P.B., D.L.B., E.G., D.A.M., E.B., M.S.); Tokai University School of Medicine; Institute of Medical Science, Isehara, Japan (S.G.); FACT, DHU-FIRE INSERM Unité 1148, Assistance Publique-Hôpitaux de Paris and Université Paris Diderot, Paris, France, and NHLI Imperial College, Royal Brompton Hospital, London, UK (P.G.S.); University of Sheffield, United Kingdom (R.F.S.); Division of Cardiology, Newark Beth Israel Medical Center, Rutgers-New Jersey Medical School, Newark (M.C.); Brigham and Women's Hospital and Harvard Clinical Research Institute, Harvard Medical School, Boston, MA (L.M.); CWZ Hospital, Nijmegen, The Netherlands (T.O.O.); Cardiology Research and Production complex MH RF, Moscow, Russia (M.R.); Internal Cardiology Department, University Hospital and Medical faculty, Brno, Czech Republic (J.S.); Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea (K.-B.S.); Heart Institute, Intervention Center, People Hospital of Peking University, China (D.H.); Life Fourways Hospital, Randburg, South Africa (A.J.D.); and AstraZeneca, Mölndal, Sweden (E.J., P.H.). mbonaca@partners.org.
  • 2From TIMI Study Group, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (M.P.B., D.L.B., E.G., D.A.M., E.B., M.S.); Tokai University School of Medicine; Institute of Medical Science, Isehara, Japan (S.G.); FACT, DHU-FIRE INSERM Unité 1148, Assistance Publique-Hôpitaux de Paris and Université Paris Diderot, Paris, France, and NHLI Imperial College, Royal Brompton Hospital, London, UK (P.G.S.); University of Sheffield, United Kingdom (R.F.S.); Division of Cardiology, Newark Beth Israel Medical Center, Rutgers-New Jersey Medical School, Newark (M.C.); Brigham and Women's Hospital and Harvard Clinical Research Institute, Harvard Medical School, Boston, MA (L.M.); CWZ Hospital, Nijmegen, The Netherlands (T.O.O.); Cardiology Research and Production complex MH RF, Moscow, Russia (M.R.); Internal Cardiology Department, University Hospital and Medical faculty, Brno, Czech Republic (J.S.); Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea (K.-B.S.); Heart Institute, Intervention Center, People Hospital of Peking University, China (D.H.); Life Fourways Hospital, Randburg, South Africa (A.J.D.); and AstraZeneca, Mölndal, Sweden (E.J., P.H.).

Abstract

BACKGROUND:

In the PEGASUS-TIMI 54 trial (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), ticagrelor reduced the risk of major adverse cardiovascular events when added to low-dose aspirin in stable patients with prior myocardial infarction, resulting in the approval of ticagrelor 60 mg twice daily for long-term secondary prevention. We investigated the incidence of stroke, outcomes after stroke, and the efficacy of ticagrelor focusing on the approved 60 mg twice daily dose for reducing stroke in this population.

METHODS:

Patients were followed for a median of 33 months. Stroke events were adjudicated by a central committee. Data from similar trials were combined using meta-analysis.

RESULTS:

Of 14 112 patients randomly assigned to placebo or ticagrelor 60 mg, 213 experienced a stroke; 85% of these strokes were ischemic. A total of 18% of strokes were fatal and another 15% led to either moderate or severe disability at 30 days. Ticagrelor significantly reduced the risk of stroke (hazard ratio, 0.75; 95% confidence interval, 0.57-0.98; P=0.034), driven by a reduction in ischemic stroke (hazard ratio, 0.76; 95% confidence interval, 0.56-1.02). Hemorrhagic stroke occurred in 9 patients on placebo and 8 patients on ticagrelor. A meta-analysis across 4 placebo-controlled trials of more intensive antiplatelet therapy in 44 816 patients with coronary disease confirmed a marked reduction in ischemic stroke (hazard ratio, 0.66; 95% confidence interval, 0.54-0.81; P=0.0001).

CONCLUSIONS:

High-risk patients with prior myocardial infarction are at risk for stroke, approximately one-third of which are fatal or lead to moderate-to-severe disability. The addition of ticagrelor 60 mg twice daily significantly reduced this risk without an excess of hemorrhagic stroke but with more major bleeding. In high-risk patients with coronary disease, more intensive antiplatelet therapy should be considered not only to reduce the risk of coronary events, but also of stroke.

CLINICAL TRIAL REGISTRATION:

URL: http://www.clinicaltrials.gov. Unique Identifier: NCT01225562.

KEYWORDS:

hemorrhagic stroke; ischemic stroke; platelet aggregation inhibitors; secondary prevention; stroke; thrombosis; ticagrelor

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