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Circulation. 2009 Jun 9;119(22):2877-85. doi: 10.1161/CIRCULATIONAHA.108.832139. Epub 2009 May 26.

Apixaban, an oral, direct, selective factor Xa inhibitor, in combination with antiplatelet therapy after acute coronary syndrome: results of the Apixaban for Prevention of Acute Ischemic and Safety Events (APPRAISE) trial.

Collaborators (186)

Wallentin L, Harrington RA, Alexander JH, Becker RC, Bhatt DL, Cools F, Crea F, Darius H, Dellborg M, Fox KA, Goodman SG, Huber K, Husted S, Lewis BS, Lopez-Sendon J, Mohan P, Montalescot G, Ruda M, Ruzyllo W, Verheugt F, Simoons M, Boersma E, DeLemos J, Spencer F, Lang I, Drexel H, Van Mieghem W, El Allaf D, Bartunek J, Vermeersch P, Schoors D, Missault L, Klinke WP, Constance C, Gosselin G, Theroux P, Kouz S, Burton JR, Bakbak AI, Velianou J, Hui W, Sussex B, Senaratne MP, Quan VH, Harnarine C, Sridhar K, Kafka H, Polasek P, Bhargava R, Grande P, Nielsen T, Jensen JS, Tuxen C, Rokkedal J, Gotzsche L, May O, Vigholt E, Egstrup K, Cottin Y, Mirode A, Elbaz M, Coste P, Gacem K, Guerin P, Demarcq JM, Grollier G, Vöhringer HF, Buerke M, Olbrich HG, Horacek T, Klues H, Gulba D, Drexler H, Zeymer U, Schoeller R, Weiss AT, Hayek T, Shotan A, Butnaru A, Kracoff OH, Lotan C, Turgeman Y, Hussein O, Zeltser D, Arbel J, Omary M, Solodky A, Zimlichman R, Pluta W, Kawecka-Jaszcz K, Trusz-Gluza M, Krzeminska-Pakula M, Kubica J, Kuc K, Buszman P, Rynkiewicz A, Musial W, Hoffmann A, Pulkowski G, Jaworska K, Piwowarska W, Boyarkin M, Barbarash O, Reshetko O, Bokarev I, Kostenko V, Boldueva S, Sherenkov A, Khrustalev O, Zateyshchikov DA, Shlyakhto E, Gratsiansky N, Yakusevich V, Glezer M, Perepech N, Kisliak O, Ardashev V, De Teresa Galvan E, Armada Romero ER, Figueras Bellot J, Gonzalez Juanatey JR, Cequier AR, Bayón Fernández J, Camprubi Portau M, Antorrena Miranda I, Cruz Fernández J, Blanco Varela J, Goiriena Seijo P, Barriales Alvarez V, Salvador Sanz A, Worner F, Sancho Jaldón M, Vigil-Escalera Gonzalez P, Rasmanis G, Ryttberg B, Oldgren J, Lycksell M, Hansen O, Herlitz J, Malmqvist K, Storey RF, Lewis PS, Moriarty A, Gershlick AH, Beatt K, Senior R, Pye M, Alamgir F, Adgey J, Butler R, Saltissi S, Wong YK, Flores E, Wickemeyer W, Cohen MG, Cragg DR, Gilchrist I, Campbell C, Staniloae CS, Halpern S, Clemson BS, Mahaffey KW, Davis B, Kipperman R, Tobiansky J, McKendall G, Dauber I, Taylor K, Mehra A, Skelding KA, Vijayaraghavan K, Mines M, Tamberella M, Applegate R, Kaplan K, Peberdy MA, Schultz R, Parr KL, Kadekar S, Tee H, Bailey SR, Yakubov S, Niederman A, Kenton DM, Arzola F, Seagle R.

Author information

1
Duke Clinical Research Institute, Duke University Medical Center, DUMC Box 3850, Durham, NC 27715, USA. john.h.alexander@duke.edu

Abstract

BACKGROUND:

After an acute coronary syndrome, patients remain at risk of recurrent events. Apixaban, an oral direct factor Xa inhibitor, is a novel anticoagulant that may reduce these events but also poses a risk of bleeding.

METHODS AND RESULTS:

Apixaban for Prevention of Acute Ischemic and Safety Events (APPRAISE) was a phase 2, double-blind, placebo-controlled, dose-ranging study. Patients (n=1715) with recent ST-elevation or non-ST-elevation acute coronary syndrome were randomized to 6 months of placebo (n=611) or 1 of 4 doses of apixaban: 2.5 mg twice daily (n=317), 10 mg once daily (n=318), 10 mg twice daily (n=248), or 20 mg once daily (n=221). Nearly all patients received aspirin; 76% received clopidogrel. The primary outcome was International Society of Thrombosis and Hemostasis major or clinically relevant nonmajor bleeding. A secondary outcome was cardiovascular death, myocardial infarction, severe recurrent ischemia, or ischemic stroke. At the recommendation of the Data Monitoring Committee, the 2 higher-dose apixaban arms were discontinued because of excess total bleeding. Compared with placebo, apixaban 2.5 mg twice daily (hazard ratio, 1.78; 95% confidence interval, 0.91 to 3.48; P=0.09) and 10 mg once daily (hazard ratio, 2.45; 95% confidence interval, 1.31 to 4.61; P=0.005) resulted in a dose-dependent increase in major or clinically relevant nonmajor bleeding. Apixaban 2.5 mg twice daily (hazard ratio, 0.73; 95% confidence interval, 0.44 to 1.19; P=0.21) and 10 mg once daily (hazard ratio, 0.61; 95% confidence interval, 0.35 to 1.04; P=0.07) resulted in lower rates of ischemic events compared with placebo. The increase in bleeding was more pronounced and the reduction in ischemic events was less evident in patients taking aspirin plus clopidogrel than in those taking aspirin alone.

CONCLUSIONS:

We observed a dose-related increase in bleeding and a trend toward a reduction in ischemic events with the addition of apixaban to antiplatelet therapy in patients with recent acute coronary syndrome. The safety and efficacy of apixaban may vary depending on background antiplatelet therapy. Further testing of apixaban in patients at risk of recurrent ischemic events is warranted.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00313300.

[Indexed for MEDLINE]

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