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

Thrombosis Journal

Hafsa Mohiuddin¹  Ameer Hamza²  Irbaz B Riaz³  Maaz B Badshah⁴  Talha Riaz¹  Haris Riaz¹  Faryal Tahir¹ 

[1] Dow Medical College, Dow University of Health Sciences, Baba-e-Urdu Road, Karachi, Pakistan;Quaid-e-Azam Medical College, Bahawalpur, Pakistan;Department of Medicine, University of Arizona, Arizona, USA;Department of Medicine, Indiana University, Indianapolis, Indiana, USA

关键词: Systematic review;    Critically ill patients;    Venous thromboembolism;    Atrial fibrillation;    Acute coronary syndrome;    Hip replacement;    Knee replacement;    Orthopedic surgery;    Dabigatran;    Rivaroxaban;    Apixaban;    Oral anticoagulants;    Vitamin K antagonists;   

Others  :  838511
DOI  :  10.1186/1477-9560-11-18

 received in 2013-01-15, accepted in 2013-08-25,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Tahir et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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