Apixaban with Antiplatelet Therapy after Acute Coronary Syndrome

被引：792

作者：

Alexander, John H. ^{[1
]}

Lopes, Renato D. ^{[1
]}

James, Stefan ^{[2
]}

Kilaru, Rakhi ^{[1
]}

He, Yaohua ^{[3
]}

Mohan, Puneet ^{[3
]}

Bhatt, Deepak L. ^{[4
,5
]}

Goodman, Shaun ^{[6
]}

Verheugt, Freek W. ^{[7
]}

Flather, Marcus ^{[8
,29
]}

Huber, Kurt ^{[9
]}

Liaw, Danny ^{[3
]}

Husted, Steen E. ^{[10
]}

Lopez-Sendon, Jose ^{[11
]}

De Caterina, Raffaele ^{[12
,13
]}

Jansky, Petr ^{[14
]}

Darius, Harald ^{[15
]}

Vinereanu, Dragos ^{[16
]}

Cornel, Jan H. ^{[17
]}

Cools, Frank ^{[18
]}

Atar, Dan ^{[19
]}

Luis Leiva-Pons, Jose ^{[20
]}

Keltai, Matyas ^{[21
]}

Ogawa, Hisao ^{[22
]}

Pais, Prem ^{[23
]}

Parkhomenko, Alexander ^{[24
]}

Ruzyllo, Witold ^{[25
]}

Diaz, Rafael ^{[26
]}

White, Harvey ^{[27
]}

Ruda, Mikhail ^{[28
]}

Geraldes, Margarida ^{[3
]}

Lawrence, Jack ^{[3
]}

Harrington, Robert A. ^{[1
]}

Wallentin, Lars ^{[2
]}

机构：

[1] Duke Univ, Duke Clin Res Inst, Med Ctr, Durham, NC 27715 USA

[2] Uppsala Clin Res Ctr, Uppsala, Sweden

[3] Bristol Myers Squibb Co, Princeton, NJ USA

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

[5] Vet Affairs Boston Healthcare Syst, Boston, MA USA

[6] Canadian Heart Res Ctr, Toronto, ON, Canada

[7] Onze Lieve Vrouw Hosp, Amsterdam, Netherlands

[8] Royal Brompton Hosp, Clin Trials & Evaluat Unit, London, England

[9] Wilhelminenspital Stadt Wien, Vienna, Austria

[10] Aarhus Univ Hosp, Dept Cardiol & Med A, Aarhus Amtssygehus, DK-8000 Aarhus, Denmark

[11] Hosp Univ La Paz, Madrid, Spain

[12] Univ G DAnnunzio, Inst Cardiol, Chieti, Italy

[13] Univ G DAnnunzio, Univ Cardiol Div, Chieti, Italy

[14] Motol Univ Hosp, Prague, Czech Republic

[15] Neukoelln Med Ctr, Berlin, Germany

[16] Univ Hosp Bucharest, Bucharest, Romania

[17] Med Ctr Alkmaar, Alkmaar, Netherlands

[18] Acad Ziekenhuis Klina, Brasschaat, Belgium

[19] Oslo Univ Hosp, Oslo, Norway

[20] Hosp Cent Dr Ignacio Morones Prieto, San Luis Potosi, Mexico

[21] Hungarian Inst Cardiol, Budapest, Hungary

[22] Kumamoto Univ, Kumamoto, Japan

[23] St Johns Med Coll, Bangalore, Karnataka, India

[24] Inst Cardiol, Kiev, Ukraine

[25] Inst Cardiol, Warsaw, Poland

[26] ECLA Estudios Cardiol Latinoamer, Rosario, Santa Fe, Argentina

[27] Auckland City Hosp, Green Lane Cardiovasc Res Unit, Auckland, New Zealand

[28] Cardiol Res Ctr, Moscow, Russia

[29] Harefield NHS Fdn Trust, London, England

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2011年 / 365卷 / 08期

关键词：

FACTOR XA INHIBITOR; HIGH-RISK PATIENTS; MYOCARDIAL-INFARCTION; DOUBLE-BLIND; ASPIRIN; CLOPIDOGREL; WARFARIN; THROMBOPROPHYLAXIS; ENOXAPARIN; INTERVENTION;

D O I：

10.1056/NEJMoa1105819

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background Apixaban, an oral, direct factor Xa inhibitor, may reduce the risk of recurrent ischemic events when added to antiplatelet therapy after an acute coronary syndrome. Methods We conducted a randomized, double-blind, placebo-controlled clinical trial comparing apixaban, at a dose of 5 mg twice daily, with placebo, in addition to standard antiplatelet therapy, in patients with a recent acute coronary syndrome and at least two additional risk factors for recurrent ischemic events. Results The trial was terminated prematurely after recruitment of 7392 patients because of an increase in major bleeding events with apixaban in the absence of a counterbalancing reduction in recurrent ischemic events. With a median follow-up of 241 days, the primary outcome of cardiovascular death, myocardial infarction, or ischemic stroke occurred in 279 of the 3705 patients (7.5%) assigned to apixaban (13.2 events per 100 patient-years) and in 293 of the 3687 patients (7.9%) assigned to placebo (14.0 events per 100 patient-years) (hazard ratio with apixaban, 0.95; 95% confidence interval [CI], 0.80 to 1.11; P = 0.51). The primary safety outcome of major bleeding according to the Thrombolysis in Myocardial Infarction (TIMI) definition occurred in 46 of the 3673 patients (1.3%) who received at least one dose of apixaban (2.4 events per 100 patient-years) and in 18 of the 3642 patients (0.5%) who received at least one dose of placebo (0.9 events per 100 patient-years) (hazard ratio with apixaban, 2.59; 95% CI, 1.50 to 4.46; P = 0.001). A greater number of intracranial and fatal bleeding events occurred with apixaban than with placebo. Conclusions The addition of apixaban, at a dose of 5 mg twice daily, to antiplatelet therapy in high-risk patients after an acute coronary syndrome increased the number of major bleeding events without a significant reduction in recurrent ischemic events. (Funded by BristolMyers Squibb and Pfizer; APPRAISE-2 ClinicalTrials. gov number, NCT00831441.)

引用

页码：699 / 708

页数：10

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