Physicians' Academy for Cardiovascular Education

New oral anticoagulants for preventing venous thromboembolism

Literature - Gómez-Outes A et al. BMJ. 2012;344:e3675. doi: 10.1136/bmj.e3675.

Dabigatran, rivaroxaban, or apixaban versus enoxaparin for thromboprophylaxis after total hip or knee replacement: systematic review, meta-analysis, and indirect treatment comparisons.


Gómez-Outes A, Terleira-Fernández AI, Suárez-Gea ML, Vargas-Castrillón E.
BMJ. 2012;344:e3675. doi: 10.1136/bmj.e3675.


Background

Venous thromboembolism (VTE) is the third cause of death from cardiovascular causes, after myocardial infarction and stroke [1]. VTE is an important problem in patients admitted to hospital, including patients undergoing major orthopaedic surgery [2,3]. New oral anticoagulants are available for VTE prophylaxis in patients undergoing total hip or knee replacement surgery.

In this study, data from randomised controlled trials of the new oral anticoagulants for prophylaxis against venous thromboembolism in patients undergoing total hip or knee replacement were systematically reviewed and meta-analysed. Direct comparisons were made with enoxaparin and indirect comparisons between the new oral anticoagulants on the clinical outcomes of symptomatic venous thromboembolism, bleeding, and death.


Main results

  • Rivaroxaban led to significantly lower rates of symptomatic VTE than enoxaparin at the cost of significantly increased bleeding
  • Both apixaban and dabigatran were as effective as enoxaparin in preventing VTE; apixaban had a lower risk of bleeding
  • There was no difference in efficacy with regard to the net clinical endpoint (composite of symptomatic VTE, major bleeding, and all cause mortality)

NOACs: symptomatic VTE and risk of bleeding


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Conclusion

A higher efficacy of the new type of anticoagulant was generally associated with a higher bleeding tendency; the new anticoagulants did not differ significantly for efficacy and safety.



Editorial comment [4]

“Readers should take away four important conclusions. Firstly, we are reaching the point of diminishing returns with newer anticoagulants for preventing venous thromboembolism. Pushing thrombosis rates lower causes more bleeding. Secondly, patient preferences should be considered when making decisions about prophylaxis against venous thromboembolism. Some patients might prefer to receive a two unit blood transfusion rather than develop deep vein thrombosis, which requires months of anticoagulation and can result in post-thrombotic syndrome or pulmonary embolism. Others might prefer a symptomatic deep vein thrombosis, which can be identified and treated, rather than a devastating haemorrhagic stroke. Thirdly, in a real world setting effectiveness may differ greatly because adherence to drug regimens may vary as a result of differences in the route of administration, frequency, duration of treatment, and side effects. Fourthly, a zero rate of venous thromboembolism is an unattainable goal. A more reasonable and attainable goal is to eliminate preventable harm—defined as venous thromboembolism associated with suboptimal prophylaxis.”


References

1. Mackman N. Triggers, targets and treatments for thrombosis. Nature 2008;451:914-8.
2. Geerts WH, Bergqvist D, Pineo GF, et al. Prevention of venous thromboembolism: American College of Chest Physicians evidence-based clinical practice guidelines (8th ed). Chest 2008;133(6 suppl):S381-453.
3. White RH, Zhou H, Romano PS. Incidence of symptomatic venous thromboembolism after different elective or urgent surgical procedures. Thromb Haemost 2003;90:446-55.
4. Haut ER, Lau BD, Streiff MB. New oral anticoagulants for preventing venous thromboembolism. BMJ. 2012;344:e3820. doi: 10.1136/bmj.e3820.


Abstract

Objective:
To analyse clinical outcomes with new oral anticoagulants for prophylaxis against venous thromboembolism after total hip or knee replacement.

Design:
Systematic review, meta-analysis, and indirect treatment comparisons.

Data sources:
Medline and CENTRAL (up to April 2011), clinical trials registers, conference proceedings, and websites of regulatory agencies.
Study selection: Randomised controlled trials of rivaroxaban, dabigatran, or apixaban compared with enoxaparin for prophylaxis against venous thromboembolism after total hip or knee replacement. Two investigators independently extracted data. Relative risks of symptomatic venous thromboembolism, clinically relevant bleeding, deaths, and a net clinical endpoint (composite of symptomatic venous thromboembolism, major bleeding, and death) were estimated using a random effect meta-analysis. RevMan and ITC software were used for direct and indirect comparisons, respectively.

Results:
16 trials in 38 747 patients were included. Compared with enoxaparin, the risk of symptomatic venous thromboembolism was lower with rivaroxaban (relative risk 0.48, 95% confidence interval 0.31 to 0.75) and similar with dabigatran (0.71, 0.23 to 2.12) and apixaban (0.82, 0.41 to 1.64). Compared with enoxaparin, the relative risk of clinically relevant bleeding was higher with rivaroxaban (1.25, 1.05 to 1.49), similar with dabigatran (1.12, 0.94 to 1.35), and lower with apixaban (0.82, 0.69 to 0.98). The treatments did not differ on the net clinical endpoint in direct or indirect comparisons.

Conclusions:
A higher efficacy of new anticoagulants was generally associated with a higher bleeding tendency. The new anticoagulants did not differ significantly for efficacy and safety

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