Table 35.

Recommendations and Levels of Evidence for Anticoagulation for AF

	COR	LOE	GOR (MINDS)	LOE (MINDS)
Selecting between DOACs and warfarin
Warfarin is recommended for stroke prevention in AF patients with moderate‐to‐severe mitral stenosis ²⁶⁰ , ²⁶¹ , ²⁶² , ²⁶³ , ³³⁶	I	B	A	IVa
Warfarin is recommended for stroke prevention in AF patients with mechanical heart valves ²³⁸ , ²⁶⁰ , ²⁶¹ , ²⁶² , ²⁶³ , ³³⁶	I	B	A	II
When oral anticoagulation is started in a patient with AF who is eligible for DOACs (dabigatran, rivaroxaban, apixaban, or edoxaban), a DOAC is recommended in preference to warfarin ²⁶⁰ , ²⁶¹ , ²⁶² , ²⁶³ , ³³⁶ , ³³⁷	I	A	A	I
When patients are treated with warfarin, TTR should be kept as high as possible* ³³⁸ , ³³⁹ , ³⁴⁰ , ³⁴¹ , ³⁴²	I	A	A	II
AF patients already on treatment with warfarin may be considered for DOAC treatment if TTR is not well controlled despite good adherence (except for cases of contraindications to DOACs) ²⁶⁰ , ²⁶² , ³³⁶ , ³³⁷ , ³⁴³	IIa	A	A	II
Selection of DOACs
For patients with high risk of bleeding, consider agent/dose of DOAC that was significantly lower than warfarin in the large‐scale clinical trials (apixaban, dabigatran 110 mg bid, edoxaban) ³³⁷ , ³⁴⁶ , ³⁴⁸ , ³⁴⁹	IIa	A	B	II
Coagulation assay during warfarin treatment
Optimal range of PT‐INR under warfarin therapy in NVAF patients without a history of ischemic stroke and having low thromboembolic risks (i.e., CHADS₂ score ≤2 points) is 1.6–2.6 irrespective of age ³⁵⁰ , ³⁵¹ , ³⁵²	IIa	B	B	IVa
Optimal range of PT‐INR under warfarin therapy in NVAF patients with a history of ischemic stroke or having high thromboembolic risks (i.e., CHADS₂ score ≥3 points, or cancer patients) is 1.6–2.6 in elderly patients (age ≥70 years) and 2.0–3.0 in younger patients (age <70 years). Even in elderly patients, INR should be kept ≥2.0 as much as possible, unless it threatens the safety for bleeding ³⁵³ , ³⁵⁴ , ³⁵⁵	IIa	B	B	IVa
Blood sampling during long‐term follow‐up
CCr (for apixaban, serum creatinine, body weight, and age) should be evaluated before DOACs are started as judgement for contraindications or dose reduction ³⁴⁶ , ³⁴⁸ , ³⁴⁹	I	A	B	II
Considering the pathogenesis or patient characteristics that possibly decrease coagulation activity (hemophilia, blood type O, etc.), coagulation tests before starting DOACs should be evaluated ³⁵⁶ , ³⁵⁷	IIa	C	B	IVa
After DOACs are started, blood tests (renal function, liver function, hemoglobin, etc.) should be done at least once per 12 months ²¹ , ³³⁰ , ³⁵⁸	IIa	C	B	V
In elderly patients (≥75 years) or frail patients, blood tests (renal function, liver function, hemoglobin, etc.) should be done at least once per 6 months ³³⁰	IIa	C	C1	VI
In patients with CCr <60 mL/min, blood test (renal function, liver function, hemoglobin, etc.) should be done at least once per X months (X=CCr/10) ³³⁰	IIa	C	C1	VI

*It has been reported that the threshold TTR under warfarin therapy that reduces mortality compared with no anticoagulation is ≥60% and that yielding better cost‐effective medical care compared with DOACs was ≥65–90% (variation according to the referenced DOAC). ³⁵⁹ However, the TTR should always be targeted at 100% and thresholds above should be regarded as the least acceptable levels.

Abbreviation: AF, atrial fibrillation; CCr, creatinine clearance; COR, class of recommendation; DOAC, direct oral anticoagulant; GOR, grade of recommendation; LOE, level of evidence; MINDS, Medical Information Network Distribution Service; NVAF, non‐valvular atrial fibrillation; PT‐INR, prothrombin time‐international normalized ratio; TTR, time in therapeutic range.