Review
The New Oral Anticoagulants in Clinical Practice

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Abstract

Vitamin K antagonists were the only class of oral anticoagulants available to clinicians for decades. However, with the US Food and Drug Administration approval of new oral anticoagulants, such as dabigatran, rivaroxaban, and apixaban, clinicians now have a broader choice. Given the recent approval and availability of these medications, several questions arise while deciding which of them would be best suited for a particular patient. This article provides a concise review for clinicians entailing the main studies that evaluated the efficacy and safety of these drugs, their pharmacokinetic and pharmacodynamic properties, and a practical approach to their clinical use. For this review, we conducted searches of PubMed and MEDLINE for articles published between January 1, 2000, and January 30, 2013, using the following search terms: oral anticoagulants, dabigatran, apixaban, rivaroxaban, novel anticoagulants, bleeding complications, management of bleeding complications, pharmacodynamics, and pharmacokinetics. Studies published in English were selected for inclusion in this review, as were additional articles identified from bibliographies.

Section snippets

Dabigatran

Dabigatran etexilate (Pradaxa) is the first oral direct thrombin inhibitor to be approved by the US Food and Drug Administration (FDA).

Rivaroxaban

Rivaroxaban (Xarelto) is the first oral direct coagulation factor Xa inhibitor approved for clinical use in the United States.

Apixaban

Apixaban (Eliquis) is an oral direct coagulation factor Xa inhibitor approved for clinical use in the United States.

Drug Interactions With NOAs

The NOAs have a low potential for drug interactions. Dabigatran etexilate, the prodrug, is a substrate of the P-glycoprotein (P-gp) efflux transporter. Hence, its plasma concentration increases with strong P-gp inhibitors (amiodarone, verapamil, clarithromycin, and ketoconazole) and reduces with potent P-gp inducers (rifampicin, carbamazepine, or phenytoin)35, 36; although no significant influence on its efficacy or safety has been reported, dosage adjustment may be needed.37 No dabigatran dose

Laboratory Testing and Monitoring for the NOAs

Given their rapid onset of action, stable pharmacokinetic properties, and lack of significant drug interactions, the NOAs do not require coagulation monitoring. However, overdoses, emergency perioperative settings, and bleeding events may warrant an assessment of the degree of anticoagulation. Table 5 summarizes the effects of the NOAs and warfarin on various coagulation parameters.

Prothrombin time (PT) is relatively insensitive at therapeutic levels of dabigatran compared with rivaroxaban and

Switching Therapies

Safely switching patients between anticoagulants is a frequent task faced by clinicians managing their patients’ anticoagulation needs. Suggested approaches are summarized in Table 6.39, 40, 50 The underlying factor that determines this approach is mainly based on accurate assessment of renal function.

Perioperative Management

Perioperative management of the NOAs is based on the urgency of the procedure, level of bleeding risk, and current renal function.39, 40, 50 The decision to stop treatment in nonurgent or elective surgery should depend on the risk of bleeding vs thrombosis.

Acute Stroke Requiring Thrombolytics

The safety of administration of thrombolytics in patients receiving concurrent NOAs is not established and poses a very high risk of bleeding. Anecdotal reports have documented the successful use of thrombolytics in patients taking dabigatran who were at least 7 hours past their last dose.51, 52 Similar reports with rivaroxaban and apixaban are lacking.

Cardioversion

For patients with AF of more than 48 hours' duration, therapeutic anticoagulation for at least 3 weeks before and 4 weeks after cardioversion is

Management of Bleeding Complications/Overdose

Lack of specific agents that reverse the anticoagulant effect complicates the management of NOA-associated bleeding events or the periprocedural reversal of anticoagulation. Management of minor bleeding, eg, epistaxis, consists of addressing the potential anatomical defects, eg, cauterization or nasal packing. The decision to hold the next dose of drug will hinge on the comorbidities and assessment of risks of drug discontinuation. Given the relatively short half-lives of the NOAs in patients

Choosing an Oral Anticoagulant

When identifying a long-term oral anticoagulant for a patient, it is important to adopt a personalized approach.68 The NOAs are not all superior in terms of efficacy compared with warfarin; hence, patients who are stable with warfarin therapy with acceptable/minimal complications will not benefit from switching to an NOA. Warfarin remains the standard of care for the management of patients with valvular AF or mechanical heart valves until further safety and efficacy data regarding the use of

Conclusion

The advent of NOAs represents a major development in the field of medicine. After more than half a century in which warfarin was the only oral anticoagulant available, the discovery of these agents has provided us with more options. Several more oral anticoagulants are in the development pipeline (Supplemental Table; available online at http://www.mayoclinicproceedings.org), and their use will only increase in the years to come. As we accumulate more experience with these agents, we will need

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