From 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.).
Circulation. 2016 Sep 20;134(12):861-71. doi: 10.1161/CIRCULATIONAHA.116.024637. Epub 2016 Aug 30.
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.
背景：在 PEGASUS-TIMI 54 试验（使用替格瑞洛对比安慰剂用于既往心肌梗死患者的心血管事件预防-血栓溶解治疗的心肌梗死 54）中，与低剂量阿司匹林相比，替格瑞洛降低了稳定型既往心肌梗死患者的主要不良心血管事件风险，导致替格瑞洛 60mg，每日 2 次获批用于此类患者的长期二级预防。我们针对该人群，研究了卒中的发生率、卒后的结局以及替格瑞洛的疗效，重点关注获批的 60mg，每日 2 次剂量降低卒中风险的情况。
方法：患者中位随访 33 个月。卒中事件由一个中心委员会裁定。使用荟萃分析合并来自类似试验的数据。
结果：在 14112 名随机分配至安慰剂或替格瑞洛 60mg 的患者中，有 213 例发生卒中；其中 85%为缺血性卒中。总的来说，18%的卒中是致命性的，另有 15%导致 30 天内出现中度或重度残疾。替格瑞洛显著降低了卒中风险（风险比，0.75；95%置信区间，0.57-0.98；P=0.034），这主要归因于缺血性卒中风险的降低（风险比，0.76；95%置信区间，0.56-1.02）。安慰剂组有 9 例和替格瑞洛组有 8 例发生了出血性卒中。荟萃分析了 4 项在冠心病患者中进行的更强化抗血小板治疗的安慰剂对照试验，纳入了 44816 例患者，结果证实缺血性卒中明显减少（风险比，0.66；95%置信区间，0.54-0.81；P=0.0001）。
结论：既往心肌梗死的高危患者有发生卒中的风险，其中约三分之一是致命性或导致中度至重度残疾。替格瑞洛 60mg，每日 2 次的添加使用显著降低了这种风险，而没有增加出血性卒中，但增加了主要出血。在有冠心病的高危患者中，不仅要考虑降低心血管事件风险，还要考虑降低卒中风险，应考虑更强化的抗血小板治疗。
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