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)

被引：45

作者：

Bonaca, Marc P. ^{[1
]}

Goto, Shinya ^{[2
,3
]}

Bhatt, Deepak L. ^{[1
]}

Steg, P. Gabriel ^{[4
,5
,6
]}

Storey, Robert F. ^{[7
]}

Cohen, Marc ^{[8
]}

Goodrich, Erica ^{[1
]}

Mauri, Laura ^{[9
,10
]}

Ophuis, Ton Oude ^{[11
]}

Ruda, Mikhail ^{[12
]}

Spinar, Jindrich ^{[13
]}

Seung, Ki-Bae ^{[14
]}

Hu, Dayi ^{[15
]}

Dalby, Anthony J. ^{[16
]}

Jensen, Eva ^{[17
]}

Held, Peter ^{[17
]}

Morrow, David A. ^{[1
]}

Braunwald, Eugene ^{[1
]}

Sabatine, Marc S. ^{[1
]}

机构：

[1] Harvard Med Sch, Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA

[2] Tokai Univ, Sch Med, Isehara, Kanagawa, Japan

[3] Inst Med Sci, Isehara, Kanagawa, Japan

[4] INSERM, U1148, AP HP, FACT,DHU FIRE, Paris, France

[5] Univ Paris Diderot, Paris, France

[6] Royal Brompton Hosp, NHLI Imperial Coll, London, England

[7] Univ Sheffield, Sheffield, S Yorkshire, England

[8] Rutgers New Jersey Med Sch, Newark Beth Israel Med Ctr, Div Cardiol, Newark, DE 08901 USA

[9] Brigham & Womens Hosp, Boston, MA 02115 USA

[10] Harvard Med Sch, Harvard Clin Res Inst, Boston, MA 02115 USA

[11] CWZ Hosp, Nijmegen, Netherlands

[12] Cardiol Res & Prod Complex MH RF, Moscow, Russia

[13] Univ Hosp & Med Fac, Internal Cardiol Dept, Brno, Czech Republic

[14] Catholic Univ Korea, Coll Med, Seoul St Marys Hosp, Seoul, South Korea

[15] Peking Univ, People Hosp, Heart Inst Intervent Ctr, Beijing, Peoples R China

[16] Life Fourways Hosp, Randburg, South Africa

[17] AstraZeneca, Molndal, Sweden

来源：

CIRCULATION | 2016年 / 134卷 / 12期

关键词：

hemorrhagic stroke; ischemic stroke; platelet aggregation inhibitors; secondary prevention; stroke; thrombosis; ticagrelor; DUAL ANTIPLATELET THERAPY; TRANSIENT ISCHEMIC ATTACK; RECENT LACUNAR STROKE; SECONDARY PREVENTION; ATRIAL-FIBRILLATION; CONTROLLED-TRIAL; CLOPIDOGREL; RISK; ATHEROTHROMBOSIS; OUTPATIENTS;

D O I：

10.1161/CIRCULATIONAHA.116.024637

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：861 / +

页数：21

共 21 条

[1] Effects of Clopidogrel Added to Aspirin in Patients with Recent Lacunar Stroke [J].

Benavente, Oscar R. ;

Hart, Robert G. ;

McClure, Leslie A. ;

Szychowski, Jeffrey M. ;

Coffey, Christopher S. ;

Pearce, Lesly A. .

NEW ENGLAND JOURNAL OF MEDICINE, 2012, 367 (09) :817-825

[2] Patients with prior myocardial infarction, stroke, or symptomatic peripheral arterial disease in the CHARISMA trial [J].

Bhatt, Deepak L. ;

Flather, Marcus D. ;

Hacke, Werner ;

Berger, Peter B. ;

Black, Henry R. ;

Boden, William E. ;

Cacoub, Patrice ;

Cohen, Eric A. ;

Creager, Mark A. ;

Easton, J. Donald ;

Hamm, Christian W. ;

Hankey, Graeme J. ;

Johnston, S. Claiborne ;

Mak, Koon-Hou ;

Mas, Jean-Louis ;

Montalescot, Gilles ;

Pearson, Thomas A. ;

Steg, P. Gabriel ;

Steinhubl, Steven R. ;

Weber, Michael A. ;

Fabry-Ribaudo, Liz ;

Hu, Tingfei ;

Topol, Eric J. ;

Fox, A. A. .

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2007, 49 (19) :1982-1988

[3] Comparative Determinants of 4-Year Cardiovascular Event Rates in Stable Outpatients at Risk of or With Atherothrombosis [J].

Bhatt, Deepak L. ;

Eagle, Kim A. ;

Ohman, E. Magnus ;

Hirsch, Alan T. ;

Goto, Shinya ;

Mahoney, Elizabeth M. ;

Wilson, Peter W. F. ;

Alberts, Mark J. ;

D'Agostino, Ralph ;

Liau, Chiau-Suong ;

Mas, Jean-Louis ;

Roether, Joachim ;

Smith, Sidney C., Jr. ;

Salette, Genevieve ;

Contant, Charles F. ;

Massaro, Joseph M. ;

Steg, Ph. Gabriel .

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2010, 304 (12) :1350-1357

[4] Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events [J].

Bhatt, DL ;

Fox, KAA ;

Hacke, W ;

Berger, PB ;

Black, HR ;

Boden, WE ;

Cacoub, P ;

Cohen, EA ;

Creager, MA ;

Easton, JD ;

Flather, MD ;

Haffner, SM ;

Hamm, CW ;

Hankey, GJ ;

Johnston, SC ;

Mak, KH ;

Mas, JL ;

Montalescot, G ;

Pearson, TA ;

Steg, PG ;

Steinhubl, SR ;

Weber, MA ;

Brennan, DM ;

Fabry-Ribaudo, L ;

Booth, J ;

Topol, EJ ;

Frye, RL ;

Amarenco, P ;

Brass, LM ;

Buyse, M ;

Cohen, LS ;

DeMets, DL ;

Fuster, V ;

Hart, RG ;

Marler, JR ;

McCarthy, C ;

Schoemig, A ;

Lincoff, AM ;

Brener, SJ ;

Sila, CA ;

Albuquerque, A ;

Aroutiounov, G ;

Artemiev, D ;

Atkeson, BG ;

Bartel, T ;

Basart, DCG ;

Lima, AB ;

Belli, G ;

Bordalo e Sa, AL ;

Bosch, X .

NEW ENGLAND JOURNAL OF MEDICINE, 2006, 354 (16) :1706-1717

[5] Long-Term Use of Ticagrelor in Patients with Prior Myocardial Infarction [J].

Bonaca, Marc P. ;

Bhatt, Deepak L. ;

Cohen, Marc ;

Steg, Philippe Gabriel ;

Storey, Robert F. ;

Jensen, Eva C. ;

Magnani, Giulia ;

Bansilal, Sameer ;

Fish, M. Polly ;

Im, Kyungah ;

Bengtsson, Olof ;

Ophuis, Ton Oude ;

Budaj, Andrzej ;

Theroux, Pierre ;

Ruda, Mikhail ;

Hamm, Christian ;

Goto, Shinya ;

Spinar, Jindrich ;

Nicolau, Jose Carlos ;

Kiss, Robert G. ;

Murphy, Sabina A. ;

Wiviott, Stephen D. ;

Held, Peter ;

Braunwald, Eugene ;

Sabatine, Marc S. ;

Morin, Suzanne ;

Dantzer, Emily ;

Acquilano, Dayle ;

McGuire, Rachael L. ;

Gannon, Joseph B. ;

Gershman, Elaine ;

Ahlbom, Ann Maxe ;

Boberg, Barbro ;

Abola, Maria Teresa ;

Ardissino, Diego ;

Aylward, Philip ;

Corbalan, Ramon ;

Dalby, Anthony ;

Diaz, Rafael ;

Hu, Dayi ;

Isaza, Daniel ;

Kamensky, Gabriel ;

Kiss, Robert ;

Kontny, Frederic ;

Lopez-Sendon, Jose ;

Medina, Felix ;

Montalescot, Gilles ;

Nicolau, Jose ;

Paolasso, Ernesto ;

Parkhomenko, Alexander .

NEW ENGLAND JOURNAL OF MEDICINE, 2015, 372 (19) :1791-1800

[6] Design and rationale for the 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 (PEGASUS-TIMI 54) trial [J].

Bonaca, Marc P. ;

Bhatt, Deepak L. ;

Braunwald, Eugene ;

Cohen, Marc ;

Steg, Philippe Gabriel ;

Storey, Robert F. ;

Held, Peter ;

Jensen, Eva C. ;

Sabatine, Marc S. .

AMERICAN HEART JOURNAL, 2014, 167 (04) :437-U44

[7]

Collins R, 2009, LANCET, V373, P1849, DOI 10.1016/S0140-6736(09)60503-1

[8] Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial [J].

Connolly, S. ;

Pogue, J. ;

Hart, R. ;

Pfeffer, M. ;

Hohnloser, S. ;

Chrolavicius, S. ;

Yusuf, S. .

LANCET, 2006, 367 (9526) :1903-1912

[9] Effect of Clopidogrel Added to Aspirin in Patients with Atrial Fibrillation [J].

Connolly, S. J. ;

Yusuf, S. ;

Camm, J. ;

Chrolavicius, S. ;

Commerford, P. ;

Flather, M. ;

Hart, R. G. ;

Hohnloser, S. H. ;

Joyner, C. ;

Pfeffer, M. ;

Gaudin, C. ;

Blumenthal, M. ;

Marchese, C. ;

Pogue, J. ;

Hart, R. ;

Hohnloser, S. ;

Anand, I. ;

Arthur, H. ;

Avezum, A. ;

Budaj, A. ;

Ceremuzynski, L. ;

De Caterina, R. ;

Diaz, R. ;

Dorian, P. ;

Flaker, G. ;

Fox, K. A. A. ;

Franzosi, M. G. ;

Goldhaber, S. ;

Golitsyn, S. ;

Granger, C. ;

Halon, D. ;

Hermosillo, A. ;

Hunt, D. ;

Jansky, P. ;

Karatzas, N. ;

Keltai, M. ;

Kozan, O. ;

Lanas, F. ;

Lau, P. ;

Le Heuzey, J. Y. ;

Lewis, B. S. ;

Morais, J. ;

Morillo, C. ;

Paolasso, E. ;

Peters, R. J. ;

Pfisterer, M. ;

Piegas, L. ;

Pipilis, A. ;

Sitkei, E. ;

Swedberg, K. .

NEW ENGLAND JOURNAL OF MEDICINE, 2009, 360 (20) :2066-2078

[10] Clopidogrel Added to Aspirin Adds No Benefit but Bleeding Risk in Patients With Recent Lacunar Stroke [J].

Diener, Hans-Christoph ;

Weber, Ralph .

STROKE, 2013, 44 (03) :861-863

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