Ticagrelor Versus Clopidogrel in Patients With ST-Elevation Acute Coronary Syndromes Intended for Reperfusion With Primary Percutaneous Coronary Intervention A Platelet Inhibition and Patient Outcomes (PLATO) Trial Subgroup Analysis

被引:413
作者
Steg, Philippe Gabriel [1 ,2 ,3 ]
James, Stefan [4 ,5 ]
Harrington, Robert A. [6 ]
Ardissino, Diego [7 ]
Becker, Richard C. [6 ]
Cannon, Christopher P. [8 ]
Emanuelsson, Hakan [9 ]
Finkelstein, Ariel [10 ]
Husted, Steen [11 ]
Katus, Hugo [12 ]
Kilhamn, Jan [9 ]
Olofsson, Sylvia [4 ,5 ]
Storey, Robert F. [13 ]
Weaver, Douglas [14 ]
Wallentin, Lars [4 ,5 ]
机构
[1] INSERM, U698, Paris, France
[2] Hop Bichat Claude Bernard, AP HP, F-75877 Paris 18, France
[3] Univ Paris 07, Paris, France
[4] Uppsala Univ, Uppsala Clin Res Ctr, Uppsala, Sweden
[5] Uppsala Univ, Dept Med Sci, Uppsala, Sweden
[6] Duke Clin Res Inst, Durham, NC USA
[7] Azienda Osped Univ Parma, Parma, Italy
[8] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA
[9] AstraZeneca Res & Dev, Molndal, Sweden
[10] Tel Aviv Med Ctr & Sch Med, Tel Aviv, Israel
[11] Aarhus Univ, Aarhus, Denmark
[12] Univ Klinikum Heidelberg, Heidelberg, Germany
[13] Univ Sheffield, Sheffield, S Yorkshire, England
[14] Henry Ford Hosp, Detroit, MI 48202 USA
关键词
acute coronary syndrome; hemorrhage; myocardial infarction; platelets; thrombosis; P2Y(12) RECEPTOR ANTAGONIST; 2007 FOCUSED UPDATE; MYOCARDIAL-INFARCTION; DOUBLE-BLIND; ASPIRIN; MANAGEMENT; AZD6140; ASSOCIATION; RATIONALE; EFFICACY;
D O I
10.1161/CIRCULATIONAHA.109.927582
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background-Aspirin and clopidogrel are recommended for patients with acute coronary syndromes (ACS) or undergoing coronary stenting. Ticagrelor, a reversible oral P2Y12-receptor antagonist, provides faster, greater, and more consistent platelet inhibition than clopidogrel and may be useful for patients with acute ST-segment elevation (STE) ACS and planned primary percutaneous coronary intervention. Methods and Result-Platelet Inhibition and Patient Outcomes (PLATO), a randomized, double-blind trial, compared ticagrelor with clopidogrel for the prevention of vascular events in 18 624 ACS patients. This report concerns the 7544 ACS patients with STE or left bundle-branch block allocated to either ticagrelor 180-mg loading dose followed by 90 mg twice daily or clopidogrel 300-mg loading dose (with provision for 300 mg clopidogrel at percutaneous coronary intervention) followed by 75 mg daily for 6 to 12 months. The reduction of the primary end point (myocardial infarction, stroke, or cardiovascular death) with ticagrelor versus clopidogrel (10.8% versus 9.4%; hazard ratio [HR], 0.87; 95% confidence interval, 0.75 to 1.01; P=0.07) was consistent with the overall PLATO results. There was no interaction between presentation with STE/left bundle-branch block and randomized treatment (interaction P=0.29). Ticagrelor reduced several secondary end points, including myocardial infarction alone (HR, 0.80; P=0.03), total mortality (HR, 0.82; P=0.05), and definite stent thrombosis (HR, 0.66; P=0.03). The risk of stroke, low in both groups, was higher with ticagrelor (1.7% versus 1.0%; HR, 1.63; 95% confidence interval, 1.07 to 2.48; P=0.02). Ticagrelor did not affect major bleeding (HR, 0.98; P=0.76). Conclusion-In patients with STE-ACS and planned primary percutaneous coronary intervention, the effects of ticagrelor were consistent with those observed in the overall PLATO trial.
引用
收藏
页码:2131 / 2141
页数:11
相关论文
共 27 条
[1]   2007 focused update of the ACC/AHA 2004 guidelines for the management of patients with ST-elevation myocardial infarction - A report of the American college of cardiology/American heart association task force on practice guidelines [J].
Antman, Elliott M. ;
Hand, Mary ;
Armstrong, Paul W. ;
Bates, Eric R. ;
Green, Lee A. ;
Halasyamani, Lakshmi K. ;
Hochman, Judith S. ;
Krumholz, Harlan M. ;
Lamas, Gervasio A. ;
Mullany, Charles J. ;
Pearle, David L. ;
Sloan, Michael A. ;
Smith, Sidney C., Jr. .
CIRCULATION, 2008, 117 (02) :296-329
[2]   Antithrombotics in Acute Coronary Syndromes [J].
Bonaca, Marc P. ;
Steg, Philippe Gabriel ;
Feldman, Laurent J. ;
Canales, John F. ;
Ferguson, James J. ;
Wallentin, Lars ;
Califf, Robert M. ;
Harrington, Robert A. ;
Giugliano, Robert P. .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2009, 54 (11) :969-984
[3]   Safety, tolerability, and initial efficacy of AZD6140, the first reversivle oral adenosine diphosphate receptor antagonist, compared with clopidigrel, in patients with non-ST-segment elevation acute coronary syndrome - Primary results of the DISPERSE-2 trial [J].
Cannon, Christopher P. ;
Husted, Steen ;
Harrington, Robert A. ;
Scirica, Benjamin M. ;
Emanuelsson, Hakan ;
Storey, Robert F. .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2007, 50 (19) :1844-1851
[4]   Cytochrome P450 2C19 polymorphism in young patients treated with clopidogrel after myocardial infarction: a cohort study [J].
Collet, Jean-Philippe ;
Hulot, Jean-Sebastien ;
Pena, Anna ;
Villard, Eric ;
Esteve, Jean-Baptiste ;
Silvain, Johanne ;
Payot, Laurent ;
Brugier, Delphine ;
Cayla, Guillaume ;
Beygui, Farzin ;
Bensimon, Gilbert ;
Funck-Brentano, Christian ;
Montalescot, Gilles .
LANCET, 2009, 373 (9660) :309-317
[5]   Clinical end points in coronary stent trials - A case for standardized definitions [J].
Cutlip, Donald E. ;
Windecker, Stephan ;
Mehran, Roxana ;
Boam, Ashley ;
Cohen, David J. ;
van Es, Gerrit-Anne ;
Steg, P. Gabriel ;
Morel, Marie-angele ;
Mauri, Laura ;
Vranckx, Pascal ;
McFadden, Eugene ;
Lansky, Alexandra ;
Hamon, Martial ;
Krucoff, Mitchell W. ;
Serruys, Patrick W. .
CIRCULATION, 2007, 115 (17) :2344-2351
[6]   Benefits and risks of the combination of clopidogrel and aspirin in patients undergoing surgical Revascularization for non-ST-elevation acute coronary syndrome - The Clopidogrel in Unstable Angina to prevent Recurrent Ischemic Events (CURE) trial [J].
Fox, KAA ;
Mehta, SR ;
Peters, R ;
Zhao, F ;
Lakkis, N ;
Gersh, BJ ;
Yusuf, S .
CIRCULATION, 2004, 110 (10) :1202-1208
[7]   Management of acute coronary syndromes. Variations in practice and outcome [J].
Fox, KAA ;
Goodman, SG ;
Klein, W ;
Brieger, D ;
Steg, PG ;
Dabbous, O ;
Avezum, A .
EUROPEAN HEART JOURNAL, 2002, 23 (15) :1177-1189
[8]   Acute ST-segment elevation myocardial infarction [J].
Goodman, Shaun G. ;
Menon, Venu ;
Cannon, Christopher P. ;
Steg, Gabriel ;
Ohman, E. Magnus ;
Harrington, Robert A. .
CHEST, 2008, 133 (06) :708S-775S
[9]  
Gurbel P, 2009, CIRCULATION, V120, pS1143
[10]   Pharmacodynamics, pharmacokinetics, and safety of the oral reversible P2Y12 antagonist AZD6140 with aspirin in patients with atherosclerosis:: a double-blind comparison to clopidogrel with aspirin [J].
Husted, S ;
Emanuelsson, H ;
Heptinstall, S ;
Sandset, PM ;
Wickens, M ;
Peters, G .
EUROPEAN HEART JOURNAL, 2006, 27 (09) :1038-1047