4–6 Currently, there are no major studies evaluating the use of NOACs in hip fracture surgery, minor orthopaedic procedures and non-orthopaedic surgery. 3 Rivaroxaban 10 mg daily and apixaban 2.5 mg twice daily were each superior to enoxaparin 40 mg daily with no difference in major bleeding rates. Dabigatran (150 mg and 220 mg once daily) was as effective as enoxaparin 40 mg daily at preventing any VTE and mortality of any cause, with no significant difference in major bleeding rates. Properties of the NOACs PropertyĬmax, maximum plasma concentration t½, plasma half life P-gp, permeability glycoprotein Cyp3A4, cytochrome P450 3A4 enzymeĬlinical indications Venous thromboembolic disease ProphylaxisĪlthough dabigatran, rivaroxaban and apixaban are available in Australia for primary venous thromboembolism (VTE) prophylaxis ( Table 2), approval is limited to the context of elective hip and knee replacement surgery, where they have been extensively studied. J Stroke Cerebrovasc Dis 2012 21:165–73 Table 1. Reproduced with permission from Elsevier Ltd from Uchiyama S, Ibayashi S, Matsumoto M, et al.

The properties of the different NOACs are shown in Table 1. 2 Those available include apixaban and rivaroxaban. Factor Xa inhibitors directly inhibit the enzyme responsible for thrombin formation. 1 Dabigatran, the second orally active direct thrombin inhibitor to be marketed after ximelagatran, is not associated with hepatotoxicity and has been approved for stroke prevention in atrial fibrillation and prevention of venous thromboembolism in at-risk populations. The direct thrombin inhibitors inactivate soluble and fibrin-bound thrombin and limit thrombogenesis and thrombus growth. The NOACs fall into two broad categories: direct thrombin inhibitors and the factor Xa inhibitors ( Figure 1). The purpose of this article is to provide a simple overview of the different agents and some rational guidance on their integration into our clinical practice. Three NOACs now have Therapeutic Goods Administration (TGA) approval for use in Australia and are listed on the Pharmaceutical Benefits Scheme (PBS) for subsidy. The NOACs have been evaluated for use in venous thromboembolic disease, non-valvular atrial fibrillation and several other cardiac indications. These agents have a more stable pharmacokinetic profile, have no significant food–drug interactions and fewer drug–drug interactions, and can be administered in a standard dose without the need for routine monitoring.

Ximelagatran was never approved for use in Australia.Ī number of new oral anticoagulants (NOACs) with properties that overcome the practical limitations of warfarin have recently become available. It was approved for both indications in a range of countries throughout Europe but it was associated with an unacceptable incidence of liver toxicity and was withdrawn from the market in 2006. It showed clinical efficacy in non-valvular atrial fibrillation and venous thromboembolic disease in studies conducted in 2000–2005. Ximelagatran, the first of the alternative agents to be developled, is a direct thrombin inhibitor.

Antidote for rivaroxaban overdose