Highlights
- •The results are based on data from 24,435 patients across 5 trials.
- •Apixaban is associated with a lower risk of bleeding compared with vitamin K antagonists (VKAs).
- •Apixaban may be associated with reduced all-cause mortality compared with VKAs.
- •Apixaban may represent an effective and safe alternative to the standard VKA therapy.
Apixaban is one of the new oral anticoagulants, which is prescribed as an alternative
to vitamin K antagonists (VKAs). Concerns regarding its bleeding profile persist and
require further evaluation. Therefore, we conducted a meta-analysis of randomized
controlled trials (RCTs) to compare the risks of bleeding and all-cause mortality
between apixaban and VKAs. The MEDLINE, EMBASE, and Cochrane Library of Clinical Trials
databases were systematically searched for RCTs comparing the risks of bleeding and
all-cause mortality of apixaban (2.5 or 5 mg twice daily) with those of VKAs. We included
RCTs conducted in adults and published in English or French. Data were pooled across
RCTs using random-effects meta-analytical models. Our systematic search identified
5 RCTs meeting our inclusion criteria (n = 24,435). They included patients with atrial
fibrillation (n = 18,358), total knee replacement surgery (n = 458), and venous thromboembolism
(n = 5,619). Data pooled across RCTs revealed that apixaban was associated with reduced
risks of any bleeding (relative risk [RR] 0.73, 95% confidence interval [CI] 0.59
to 0.90) and a composite of major or clinically relevant nonmajor bleeding (RR 0.60,
95% CI 0.40 to 0.88). Apixaban was also associated with a lower risk of intracranial
bleeding (RR 0.42, 95% CI 0.31 to 0.58) whereas analyses of major and minor bleeding
were inconclusive. Moreover, apixaban was associated with decreased all-cause mortality
(RR 0.89, 95% CI 0.81 to 0.99) although this finding was driven by the results of
the ARISTOTLE trial. In conclusion, our meta-analysis found that apixaban is associated
with a lower risk of bleeding than VKAs, providing some reassurance regarding its
safety.
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References
- Novel oral anticoagulants and their role in clinical practice.Pharmacotherapy. 2011; 31: 1175-1191
- Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation.Ann Intern Med. 2007; 146: 857-867
- Bleeding of new oral anticoagulants for stroke prevention in atrial fibrillation: a meta-analysis of randomized controlled trials.Cardiovasc Drugs Ther. 2013; 27: 23-35
- Warfarin discontinuation after starting warfarin for atrial fibrillation.Circ Cardiovasc Qual Outcomes. 2010; 3: 624-631
- The efficacy and safety of oral anticoagulants in warfarin-suitable patients with nonvalvular atrial fibrillation: systematic review and meta-analysis.Clin Appl Thromb Hemost. 2013; 19: 619-631
U.S. Food and Drug Administration. FDA News Release: FDA Approves Eliquis to Reduce the Risk of Stroke, Blood Clots in Patients with Non-Valvular Atrial Fibrillation. December 28th, 2012. Available at: http://www.fda.gov/%20newsevents/newsroom/pressannouncements/ucm333634.htm. Accessed on June 11, 2014.
Bristol-Myers Squibb. U.S. FDA Approves Eliquis (Apixaban) to Reduce the Risk of Blood Clots Following Hip or Knee Replacement Surgery. March 14th, 2014. Available at: http://news.bms.com/press-release/us-fda-approves-eliquis-apixaban-reduce-risk-blood-clots-following-hip-or-knee-replace. Accessed on June 12, 2014.
- Reversal of novel oral anticoagulants in patients with major bleeding.J Thromb Thrombolysis. 2013; 35: 391-398
- Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.PLoS Med. 2009; 6: e1000097
- Enhancing retrieval of best evidence for health care from bibliographic databases: calibration of the hand search of the literature.Stud Health Technol Inform. 2001; 84: 390-393
Bristol-Myers Squibb Company. Eliquis Highlights of Prescribing Information. August 2014. Available at: http://packageinserts.bms.com/pi/pi_eliquis.pdf. Accessed on November 19, 2014.
- Efficacy and safety of the oral direct factor Xa inhibitor apixaban for symptomatic deep vein thrombosis. The Botticelli DVT dose-ranging study.J Thromb Haemost. 2008; 6: 1313-1318
- Oral apixaban for the treatment of acute venous thromboembolism.N Engl J Med. 2013; 369: 799-808
- Assessing risk of bias in included studies. Cochrane Handbook for Systematic Reviews of Interventions.John Wiley & Sons, Ltd, Chichester2008: 187-241
- Inclusion of zero total event trials in meta-analyses maintains analytic consistency and incorporates all available data.BMC Med Res Methodol. 2007; 7: 5
- Apixaban versus warfarin in patients with atrial fibrillation.N Engl J Med. 2011; 365: 981-992
- The efficacy and safety of apixaban, an oral, direct factor Xa inhibitor, as thromboprophylaxis in patients following total knee replacement.J Thromb Haemost. 2007; 5: 2368-2375
- Safety and efficacy of the oral direct factor Xa inhibitor apixaban in Japanese patients with non-valvular atrial fibrillation. -The ARISTOTLE-J study-.Circ J. 2011; 75: 1852-1859
European Medicines Agency. Eliquis-EMEA/H/C/002148 -II/0014/G. Eliquis: EPAR-Product Information. September 29th, 2014. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002148/WC500107728.pdf. Accessed on November 19, 2014.
- A specific antidote for reversal of anticoagulation by direct and indirect inhibitors of coagulation factor Xa.Nat Med. 2013; 19: 446-451
- Intracranial hemorrhage and novel anticoagulants for atrial fibrillation: what have we learned?.Curr Cardiol Rep. 2014; 16: 480
- A synthetic small molecule antidote for anticoagulants.Eur Heart J. 2013; 34: 188-189
- Impact of once-daily versus twice-daily dosing frequency on adherence to chronic medications among patients with venous thromboembolism.Patient. 2013; 6: 213-224
Article info
Publication history
Published online: December 01, 2014
Accepted:
November 20,
2014
Received in revised form:
November 20,
2014
Received:
September 11,
2014
Footnotes
See page 540 for disclosure information.
Identification
Copyright
© 2015 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
