Edoxaban. Edoxaban is one of the newest Xa inhibitors that have been approved for treatment of nonvalvular AF. The recommended dose of this drug is 60 mg once daily for patients with a CrCl higher than 50 mL/min and no more than 95 mL/min; edoxaban is not recommended in patients with a CrCl higher than 95 mL/min (Table 1).8 For individuals with a CrCl of 15 to 50 mL/min, it is recommended to reduce the dose to 30 mg once daily.8

A plasma concentration of approximately 62% is observed in the peak onset period of 1 to 2 hours.8 Edoxaban is primarily excreted in the urine, and its half-life is 10 to14 hours.8 The most common side effects are bleeding and anemia.8


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Perioperative considerations. Perioperative care of a patient taking direct factor Xa inhibitors includes assessment of renal function 7 days prior to a scheduled procedure. For patients with a CrCl higher than 30 mL/min, procedures with a standard bleeding risk require that direct factor Xa inhibitors be discontinued 24 hours prior to the procedure and those with a high bleeding risk require that direct factor Xa inhibitors be discontinued 48 hours prior to the procedure (Table 2).6,7,9,10 If the patient has a CrCl of 30 mL/min or less, procedures with a standard bleeding risk require that direct factor Xa inhibitors be discontinued 48 hours prior and those with a high bleeding risk require that direct factor Xa inhibitors be discontinued 72 hours prior.6,7,9,10 After a procedure is completed, direct factor Xa inhibitors should be resumed as soon as possible, typically 12 to 24 hours after a minor procedure or 48 to 72 hours after a major procedure.6,7,9,10 In most patients taking direct factor Xa inhibitors, preoperative parenteral anticoagulation is not necessary.6,7,10


Hepatic or renal impairment. Typically, direct factor Xa inhibitors are metabolized in the kidney (approximately 25%-35%) and liver.5 Severe hepatic impairment could potentially result in accumulation of these agents to toxic levels.5 None of the Xa inhibitors have any known reversal agents at this time. There are also no current guidelines for monitoring of any of the Xa inhibitors, but there is a recommendation for prompt evaluation with any signs and symptoms of a drop in hematocrit and hemoglobin levels.6

Direct thrombin inhibitors

Direct thrombin inhibitors prevent the conversion of fibrinogen into fibrin during the coagulation cascade and ultimately prevent the development of a thrombus.11 Dabigatran etexilate was the first direct thrombin inhibitor approved by the FDA to reduce the risk of stroke and systemic embolism in patients with nonvalvular AF, in October 2010.12

The recommended dosing of dabigatran etexilate is 150 mg orally taken twice daily if CrCl is greater than 30 mL/min (Table 1).13 For patients with a CrCl of 15 mL/min to 30 mL/min, the recommended dosage is 75 mg taken orally twice daily.13 There are no recommendations for patients with a CrCl less than 15 mL/min.13 Plasma concentrations of dabigatran etexilate peak at 1 to 3 hours; the drug has a half-life of 8 hours after a single dose and 12 to 14 hours after multiple doses.11,14 It is metabolized by the liver and excreted by the kidneys.11

Clearance of dabigatran etexilate is dependent on time and renal function. For patients with a CrCl of 50 mL/min or greater, the drug should be discontinued 24 hours prior to any procedure with a standard risk of bleeding and 48 hours prior to any procedure with high risk of bleeding.11 If a patient’s CrCl is higher than 30 mL/min but lower than 50 mL/min, discontinuation of the drug should occur 48 hours before procedures with a standard risk of bleeding and 4 days before procedures with a high risk of bleeding.11 Finally, for patients with a CrCl that is less than 30 mL/min, discontinuation should occur 2 to 5 days before a procedure with a standard risk of bleeding and more than 5 days before a procedure with a high risk of bleeding.11 It should be noted that an antidote, idarucizumab, has recently been submitted for approval by the FDA for use in patients who require rapid reversal of the dabigatran etexilate.15

The most commonly reported serious adverse effect associated with dabigatran etexilate use is bleeding; however, heart attack, liver failure, and death have also been reported.16 There are no current recommendations by the FDA concerning monitoring of dabigatran etexilate, but some studies have suggested monitoring levels could decrease major bleeding risks by as much as 40%.17