Direct oral anticoagulants: Challenging prescribing scenarios in everyday practice

Article Figures & Data

TABLE 1

Direct oral anticoagulant use in extreme body weight

Condition	Body mass index or weight
Condition	≥ 50 kg/m² or > 150 kg	40–49 kg/m² or 120–150 kg	< 18.5 kg/m² or < 60 kg
Venous thromboembolism	Data limited	Apixaban and rivaroxaban may preferably be used	Data scarce, but DOACs may be used
Atrial fibrillation	Data limited	Apixaban, rivaroxaban, and dabigatran can be used	Apixaban is preferred; reduce dose to 2.5 mg twice daily if creatinine clearance > 1.5 mg/dL or age > 80, or both; other DOACs may also be considered

TABLE 2

Direct oral anticoagulant recommendations and dosages based on kidney function

Condition and direct oral anticoagulant	Creatinine clearance, mL/min
Condition and direct oral anticoagulant	< 15 or on hemodialysis	15 to < 30	30 to < 50	≥ 50
Nonvalvular atrial fibrillation
Apixaban	Not studied^{^a}	5 mg twice daily or 2.5 mg twice daily^{^b}	5 mg twice daily or 2.5 mg twice daily^{^b}	5 mg twice daily or 2.5 mg twice daily^{^b}
Edoxaban	Recommendations cannot be provided	30 mg once daily^{^c}	30 mg once daily^{^c}	60 mg once daily^{^d}
Rivaroxaban	Not studied^{^e}	Treat as moderate impairment; 15 mg once daily (not studied)	15 mg once daily	20 mg once daily
Dabigatran	Recommendations cannot be provided	75 mg twice daily^{^f}	150 mg twice daily	150 mg twice daily
Venous thromboembolism
Apixaban	No prospective clinical data on efficacy and safety	No prospective clinical data on efficacy and safety	10 mg twice daily; transition to 5 mg twice daily after 7 days	10 mg twice daily; transition to 5 mg twice daily after 7 days
Edoxaban	Recommendations cannot be provided	30 mg once daily^{^c}	30 mg once daily^{^c}	60 mg once daily^{^d}
Rivaroxaban	Avoid	No prospective clinical data on efficacy and safety	15 mg twice daily; transition to 20 mg once daily after 21 days	15 mg twice daily; transition to 20 mg once daily after 21 days
Dabigatran	Recommendations cannot be provided	Recommendations cannot be provided	150 mg twice daily	150 mg twice daily

Note: Additional adjustments needed for concomitant use of P-glycoprotein or cytochrome P450 3A4 inhibitors, or both, are not included.
↵^aExpected pharmacokinetic and pharmacodynamic profile as in ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial.²⁷
↵^bReduce dose in patients with at least 2 of the following: age ≥ 80, body weight ≤ 60 kg, serum creatinine ≥ 1.5 mg/dL.¹⁷
↵^cPatients with creatinine clearance < 30 mL/min were not included in randomized clinical trials.³¹
↵^dDo not use in patients with creatinine clearance > 95 mL/min due to increased risk of ischemic strokes.¹⁹
↵^eExpected pharmacokinetic and pharmacodynamic profile as in ROCKET AF (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation).²⁸
↵^fNot based on prospective clinical data.¹⁷
Based on information from references 17, 33, and 34.

TABLE 3

Direct oral anticoagulant dosages and precautions in liver disease

Condition and direct oral anticoagulant	Child-Pugh class
Condition and direct oral anticoagulant	A	B	C
Nonvalvular atrial fibrillation
Apixaban	5 mg twice daily or 2.5 mg twice daily^{^a}	Limited clinical experience; recommendations cannot be provided	Avoid
Edoxaban	60 mg once daily	Avoid	Avoid
Rivaroxaban	20 mg once daily	Avoid^{^b}	No clinical data available; avoid
Dabigatran	150 mg twice daily	Large intersubject variability, but no evidence of a consistent change in drug exposure; use with caution or avoid	No clinical data available; avoid
Venous thromboembolism
Apixaban	10 mg twice daily; transition to 5 mg twice daily after 7 days	Limited clinical experience; recommendations cannot be provided	Avoid
Edoxaban	60 mg once daily	Avoid	Avoid
Rivaroxaban	15 mg twice daily; transition to 20 mg once daily after 21 days	Avoid^{^b}	No clinical data available; avoid^{^b}
Dabigatran	150 mg twice daily	Large intersubject variability, but no evidence of a consistent change in drug exposure; use with caution or avoid	No clinical data available; avoid

Note: Class A is mild hepatic impairment, B is moderate impairment, and C is severe liver disease. Additional adjustments needed for concomitant use of P-glycoprotein or cytochrome P450 3A4 inhibitors, or both, are not included.
↵^aReduce dose in patients with at least 2 of the following: age ≥ 80, body weight ≤ 60 kg, serum creatinine ≥ 1.5 mg/dL.¹⁷
↵^bDrug exposure and bleeding risk may be increased.^17,37
Based on information from reference 36.

TABLE 4

Direct oral anticoagulant use for treatment of venous thromboembolism and nonvalvular atrial fibrillation after bariatric surgery

Gastric banding	All direct oral anticoagulants can be used because the gastrointestinal anatomy is preserved
Gastric sleeve	Apixaban may be a preferred option because of the intact duodenum; avoid rivaroxaban and dabigatran because they are predominantly absorbed in the stomach; edoxaban requires an acidic environment for optimal absorption, which may be altered
Roux-en-Y gastric bypass Biliopancreatic diversion with duodenal switch	All direct oral anticoagulants should be avoided due to inadequate absorption after extensive loss of the stomach and proximal small intestines