Stop that Clot! What’s New with Anticoagulation

By Kim Maryniak, PhDc, MSN, RNC-NIC, contributor

The oral anticoagulant warfarin has been used for decades as the only option for patients with multiple diagnoses. Warfarin works as a vitamin K antagonist in the body. There is a narrow therapeutic range with warfarin, as well as drug and food interactions which can affect compliance, safety, and efficacy (Gonsalves, Pruthi, & Patnaik, 2013).

Like any medication, the new oral anticoagulants each have pros and cons to be considered for each patient

Over the past several years, the Food and Drug Administration (FDA) has approved new oral anticoagulants, which work differently than warfarin. These oral anticoagulants are dabigatran (Pradaxa®), rivaroxaban (Xarelto®), and apixaban (Eliquis®). Clinical trials demonstrated safety and effectiveness with multiple conditions for each of these medications.

Dabigatran (Pradaxa®) is approved by the FDA to reduce the risk of stroke and thrombosis in patients with non-valvular atrial fibrillation (Gonsalves et al., 2013; Ipbal, 2013; Unger, 2015). It works on Factor IIa by inhibiting thrombin, both in free-form and clot-bound, as well as platelet aggregation. The inhibition of thrombin prevents thrombus formation (Boehringer Ingelheim Pharmaceuticals, 2016). Dabigatran is metabolized in the liver, and excreted in both the urine and feces (Gonsalves et al., 2013; Ipbal, 2013). There are some medications which interact with dabigatran which may require a dose adjustment, including amiodarone, clarithromycin, verapamil, carbamazepine, phenytoin, and proton pump inhibitors (Gonsalves et al., 2013; Ipbal, 2013).

Rivaroxaban (Xarelto®) is approved by the FDA for the primary prevention of venous thromboembolism (VTE) for total hip or total knee replacement patients, prevention of stroke and embolism in patients with non-valvular atrial fibrillation, treatment of VTE (including deep venous thrombosis and pulmonary embolism), and to reduce the risk of recurrent VTE after initial treatment (Gonsalves et al., 2013; Ipbal, 2013; Unger, 2015).  It works by inhibiting Factor Xa and prothrombinase, which decreases thrombin generation and indirectly inhibiting platelet aggregation (Janssen Pharmaceuticals, 2015). Rivaroxaban is also metabolized in the liver, with excretion through both urine and feces (Gonsalves et al., 2013; Ipbal, 2013). There may be some interactions with the same medications as those described with dabigatran, but no dose adjustments are required with rivaroxaban (Gonsalves et al., 2013; Ipbal, 2013).

Apixaban (Eliquis®) is approved by the FDA for the prevention of stroke and VTE in adults with non-valvular atrial fibrillation and in the primary prevention of VTE in patients with total hip and total knee replacement (Gonsalves et al., 2013; Ipbal, 2013; Unger, 2015). It works the same as rivaroxaban, by inhibiting Factor Xa and prothrombinase (Rx List, 2016). Metabolism of apixaban also occurs in the liver, and is excreted primarily through the liver, and through the urine secondarily. There are medication interactions as those described with dabigatran, which may require dose adjustments of apixaban or consideration of different medications for the patient (Gonsalves et al., 2013; Ipbal, 2013).

These new oral anticoagulants have a rapid onset of action, whereas warfarin has a slow onset of action. Food and drug interactions are minimal with the new oral anticoagulants, and do not require close laboratory monitoring. Additionally, there is no antidote for overdose of the new oral anticoagulants, whereas, warfarin overdoses can be corrected by using vitamin K as the antidote. Hemodialysis may be used with a dabigatran overdose, but is not effective with rivaroxaban or apixaban.

The new oral anticoagulants should also be avoided with severe renal insufficiency, patients who have mechanical heart valves, and during pregnancy (Gonsalves et al., 2013; Ipbal, 2013; Unger, 2015). Furthermore, these new medications have higher costs, and do not currently have any long-term safety data available, including what role they might have in hemorrhagic stroke.

The new oral anticoagulants offer options to patients other than warfarin. However, they are not for everyone, and each has its pros and cons. Just like any medication, individual considerations are required.

For more information on anticoagulation, consider these courses from RN.com: Hazards of Heparin and Heparin Induced Thrombocytopenia.

Boehringer Ingelheim Pharmaceuticals. (2016). Pradaxa: Mechanism of action.  Retrieved from https://www.pradaxapro.com/dabigatran-etexilate/mechanism-of-action
Gonsalves, W., Pruthi, R., & Patnaik, M. (2013). The new anticoagulants in clinical practice. Mayo Clinic Proceedings, 88(5), 495-511.
Ipbal, O. (2013). New oral anticoagulant drugs. Personalized Medicine, 10(5), 419-422.
Janssen Pharmaceuticals. (2015). How Xarelto works. Retrieved from https://www.xareltohcp.com/about-xarelto/about-factor-xa.html
Rx List. (2016). Eliquis. Retrieved from http://www.rxlist.com/eliquis-drug/clinical-pharmacology.htm
Unger, E. (2015). Atrial fibrillation and new oral anticoagulant drugs. Retrieved from http://www.fda.gov/Drugs/NewsEvents/ucm405148.htm

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