Non–vitamin K antagonist anticoagulants (NOACs, also called novel or direct oral anticoagulants) are commonly used to treat and prevent venous thromboembolism (VTE) and to prevent ischemic stroke in patients with nonvalvular atrial fibrillation. These agents, which include the factor Xa inhibitors rivaroxaban (Xarelto), apixaban (Eliquis), and edoxaban (Savaysa), and the competitive thrombin inhibitor dabigatran (Pradaxa), often are preferred over warfarin because of their more predictable pharmacokinetics, comparable efficacy, comparable or lower risk of major bleeding complications, fewer drug interactions, and lack of need for frequent monitoring. However, the acute care of patients taking NOACS can be challenging, because only dabigatran has an approved reversal agent, and none have readily available, reliable measurement assays. The American Heart Association (AHA) published a statement on the periprocedural and acute care management of patients taking NOACs. Here are the findings and recommendations of the AHA that are most relevant to primary care physicians.
Measurement
While all NOACs affect coagulation tests, their effect on prothrombin time and activated partial thromboplastin time is neither predictable nor an accurate reflection of the degree of anticoagulation. Instead, use the time of last drug ingestion and the patient’s creatinine clearance to estimate the anticoagulation effect. Dabigatran takes 1 hour to reach peak effect, or 2 hours if taken with food. Its half-life is 12-17 hours, on the higher end in the elderly and in those with moderate renal impairment. In those with severe renal impairment, half-life can be 28 hours. Rivaroxaban’s time to peak is 2-4 hours, and its half-life is 5-9 hours or up to 13 in the elderly. Apixaban’s time to peak is 3-4 hours and its half-life is about 12 hours. An antifactor Xa activity assay does provide a quantitative assessment of the factor Xa inhibitors.
Kidney injury
Acute kidney injury increases risk of bleeding while taking a NOAC. Monitor these patients closely and consider temporarily switching to a different anticoagulant in the setting of kidney injury.
Bleeding
Lack of reversibility is a common concern. Use 5 g of IV idarucizumab (Praxbind) to reverse dabigatran within minutes in a patient experiencing major bleeding. Hemodialysis, which removes about half of dabigatran in 4 hours, is a suitable option in acute kidney injury or in patients with a creatinine clearance under 30mL/min.
Options are more limited for the Xa inhibitors, because there are no available reversal agents and hemodialysis does not clear these highly protein-bound drugs. While data are limited, prothrombin complex concentrate may be given for patients on rivaroxaban, apixaban, or edoxaban who are experiencing an intracranial hemorrhage or other form of severe bleeding. Simply holding the NOAC is acceptable for minor bleeding.
Overdose
Activated charcoal to induce vomiting will work within 1-2 hours of drug ingestion.
Intracranial hemorrhage
Assume that a patient taking a NOAC who displays any acute neurologic change is experiencing an intracranial hemorrhage until proven otherwise. After CT confirmation, reverse dabigatran with idarucizumab, or give prothrombin complex concentrate to patients on other NOACs.
Ischemic stroke
Patients who suffer an ischemic stroke despite NOAC therapy are not candidates for tissue plasminogen activators.
The primary care physician is likely to be involved in the decision of whether, when, and for how long to resume anticoagulation therapy after a stroke. The statement says, “guidelines support withholding oral anticoagulation until 1-2 weeks after stroke among individuals with NVAF [nonvalvular atrial fibrillation], with shorter times for those with transient ischemic attack or small, nondisabling strokes and longer times for moderate to severe strokes.” In addition, it is worthwhile to consider medication nonadherence if no other etiology for the stroke is found; patients who miss doses may benefit more from warfarin because of its longer half-life.
Procedures and surgeries
Each year approximately 10% of patients on anticoagulation require surgery or other invasive procedures, and 20% require a minor procedure. To determine whether to interrupt NOAC therapy prior to a procedure, first determine the procedure’s bleeding risk. Patients undergoing procedures with low risk of bleeding, including minor dental, dermatologic, and ophthalmologic procedures, and endoscopies without biopsies, do not require interruption. For procedures with a moderate bleeding risk (including cardiac ablation, endoscopy with biopsies, radial artery catheterization) or high bleeding risk (including major surgery and cardiac catheterization via femoral artery), the patient’s thromboembolic risk should be evaluated using the medical history and the CHA2DS2 VASc score. NOACs should be stopped for 24-48 hours prior to the moderate to high-risk procedures. Dabigatran should be held for 72 hours for patients with creatinine clearance less than 50mL/min. Bridging therapy with heparin is not recommended for patients taking NOACS who are to have surgery. The decision about when to restart NOAC is based on the risk of thromboembolism and the bleeding risk of surgery.
Spinal or epidural anesthesia
Anesthesia guidelines recommend holding NOACs 3-5 days prior to the intervention, however, this increases risk of TE and studies have shown a very low incidence of hematoma in patients anticoagulated with a NOAC. For patients with a high risk of VTE, the NOAC can be resumed 12 hours post-procedure.
The bottom line
NOACS are commonly used for treatment and prophylaxis of VTE and atrial fibrillation and are often preferred over warfarin due to their more predictable pharmacokinetics, comparable efficacy, comparable or lower risk of major bleeding complications, fewer drug interactions, and lack of need for frequent monitoring. The AHA scientific statement gives guidance on managing NOACS in the face of acute bleeding as well as during and after procedures. NOACS should be stopped 24-48 hours prior to major surgeries and may be restarted based on weighing the risk of bleeding and risk of thromboembolism.
Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, and associate director of the family medicine residency program at Abington (Pa.) Jefferson Health. Dr. Oh is a third-year resident in the family medicine residency program at Abington Jefferson Health.
Reference
Raval AN et al. Management of patients on non–vitamin K antagonist oral anticoagulants in the acute care and periprocedural setting: A scientific statement from the American Heart Association. Circulation. 2017 Feb 6;135[10]:e604-e33. doi: 10.1161/CIR.0000000000000477
