Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2013 Sep 3;11(1):18.
doi: 10.1186/1477-9560-11-18.

The new oral anti-coagulants and the phase 3 clinical trials - a systematic review of the literature

Faryal Tahir  1 , Haris Riaz, Talha Riaz, Maaz B Badshah, Irbaz B Riaz, Ameer Hamza, Hafsa Mohiuddin
Affiliations

The new oral anti-coagulants and the phase 3 clinical trials - a systematic review of the literature

Faryal Tahir et al. Thromb J. .

Abstract

Background: Anticoagulation with vitamin K antagonists such as warfarin has historically been used for the long term management of patients with thromboembolic disease. However, these agents have a slow onset of action which requires bridging therapy with heparin and its analogues, which are available only in parenteral route. To overcome these limitations, new oral anticoagulants such as factor Xa inhibitors and direct thrombin inhibitors have been developed. The aim of this article is to systematically review the phase 3 clinical trials of new oral anticoagulants in common medical conditions.

Methods: We searched PubMed (Medline) from January 2007 to February 2013 using "Oral anticoagulants", "New oral anticoagulants", "Randomized controlled trial", "Novel anticoagulants", "Apixaban", "Rivaroxaban", "Edoxaban", "Dabigatran etexilate", "Dabigatran" and a combination of the above terms. The available evidence from the phase 3 RCTs was summarized on the basis of individual drug and the medical conditions categorized into "atrial fibrillation", "acute coronary syndrome", "orthopedic surgery", "venous thromboembolism" and "medically ill patients".

Results: Apixaban, rivaroxaban and dabigatran have been found to be either non-inferior or superior to enoxaparin in prophylaxis of venous thromboembolism in knee and hip replacement with similar bleeding risk, superior to warfarin for stroke prevention in atrial fibrillation with significant reduction in the risk of major bleeding, non-inferior to aspirin for reducing cardiovascular death and stroke in acute coronary syndrome with significant increase in the risk of major bleed. Rivaroxaban and dabigatran are also superior to the conventional agents in the management of symptomatic venous thromboembolism. However, compared to enoxaparin, apixaban and rivaroxaban use lead to significantly increased bleeding risk in medically ill patients. Additional studies evaluating the specific reversal agents of these new drugs for the management of life-threatening bleeding or other adverse effects are necessary.

Conclusion: Considering their pharmacological properties, their efficacy and bleeding complications, the new oral agents offer a net favourable clinical profile in orthopedic surgery, atrial fibrillation, acute coronary syndrome and increase the risk of bleeding in critically ill patients. Further studies are necessary to determine the long term safety and to identify the specific reversal agents of these new drugs.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Classification of oral anticoagulants in development. * Phase 2 Clinical Trials. ** Phase 3 Clinical Trials.
Figure 2
Figure 2
Inclusion of phase 3 clinical trials for review.
See this image and copyright information in PMC

References

    1. Eikelboom JW, Weitz JI. New anticoagulants. Circulation. 2010;121(13):1523–1532. doi: 10.1161/CIRCULATIONAHA.109.853119. - DOI - PubMed
    1. Altman R, Vidal HO. Battle of oral anticoagulants in the field of atrial fibrillation scrutinized from a clinical practice (the real world) perspective. Thromb J. 2011;9:12. - PMC - PubMed
    1. Raghavan N, Frost CE, Yu Z, He K, Zhang H, Humphreys WG, Pinto D, Chen S, Bonacorsi S, Wong PC, Zhang D. Apixaban metabolism and pharmacokinetics after oral administration to humans. Drug Metab Dispos. 2009;37(1):74–81. doi: 10.1124/dmd.108.023143. - DOI - PubMed
    1. Eriksson BI, Quinlan DJ, Weitz JI. Comparative pharmacodynamics and pharmacokinetics of oral direct thrombin and factor xa inhibitors in development. Clin Pharmacokinet. 2009;48(1):1–22. doi: 10.2165/0003088-200948010-00001. - DOI - PubMed
    1. Buller H, Deitchman D, Prins M, Segers A. 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(8):1313–1318. - PubMed