Anticoagulation for Atrial

Fibrillation (AFib) in Patients

Receiving Bruton Tyrosine
Kinase (BTK) Inhibitors

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 Anticoagulation for AFib in Patients Receiving BTK Inhibitors

Bruton kinase (BTK) inhibitors are an effective therapy in the treatment of Chronic Lymphocytic Leukemia (CLL) and are overall well tolerated; however, their use
has been associated with increased incidence of atrial fibrillation. ACC provides guidance for using anticoagulation in patients with AFib who take BTK inhibitors.1-4

Assess Feasibility for Implement

Anticoagulation Anticoagulation

Patient-specific risk factors Different CLL patients

Antiplatelet activity of BTK inhibitors Different anticoagulation steps
and drug-drug interactions Different dosing requirements

CHA2DS2-VASc Score “What If”

Scenarios and Steps

HAS-BLED Score
DOACs Prescriptions

Select the scenarios and

Antiplatelet Effects prescriptions to learn more.

Drug Interactions

More Information
Select each risk factor to learn more.
 Anticoagulation for AFib in Patients Receiving BTK Inhibitors Assess Feasibility for Anticoagulation

CHA2DS2-VASc Score
SCORE CALCULATION

Stroke Risk Factors Score

Congestive heart failure/LV dysfunction 1

Hypertension 1

Age ≥ 75 years 2

Use this score to:5-6

Diabetes Mellitus 1
Estimate the annual risk of a
thromboembolic event
Stroke/TIA/thromboembolic event 2
Guide anticoagulation decisions
Select to view more.
Vascular disease (prior MI, PAD, or aortic plaque) 1

Age 65-74 years 1

Sex category (that is, sex: female) 1

 Anticoagulation for AFib in Patients Receiving BTK Inhibitors Assess Feasibility for Anticoagulation

CHA2DS2-VASc Score

CHA2DS2-VASc Risk of ischemic Risk of stroke/TIA/

score stroke* systemic embolism*

0 0.2%
1 0.6%
2 2.2%
3 3.2%
4 4.8%
Select to go back. 5 7.2%
0.3%
Some general recommendations include:7
0.9%
Patients with mechanical valves or moderate-severe
mitral stenosis to be anticoagulated with warfarin,
2.9% regardless of the CHA2DS2-VASc score
In others, anticoagulation recommended for:
4.6%
Men with CHA2DS2-VASc ≥ 2
Women with CHA2DS2-VASc ≥ 3
6.7%
Anticoagulation recommended for paroxysmal,
10.0% persistent, or permanent AFib/flutter

6 9.7% 13.6% More Information

7 11.2% 15.7%

8 10.8% 15.2%

9 12.2% 17.4%

*Adjusted Rates of Events (% per year)

 Anticoagulation for AFib in Patients Receiving BTK Inhibitors Assess Feasibility for Anticoagulation

HAS-BLED Score

Condition Points

H - Hypertension 1

A - Abnormal renal or liver function (1 point each) 1 or 2

Use this score to estimate the risk of major
bleeding (intracranial bleeds, GI bleeds, and
S - Stroke 1
bleeds requiring transfusion) in a patient on
anticoagulation for AFib.5-6,8-10
B - Bleeding 1
Consideration of the HAS-BLED and
CHA2DS2-VASc scores → Decision to start L - Labile INRs 1
anticoagulation 5-6,8-10 Select to view more.
E - Elderly (> 65 years) 1

D - Drugs that increase the risk of bleeding or

alcohol (1 point each) 1 or 2
 Anticoagulation for AFib in Patients Receiving BTK Inhibitors Assess Feasibility for Anticoagulation

HAS-BLED Score

Bleeding events/year at risk in relation to the type of anticoagulation used and

HAS-BLED risk score

Score n Intracranial bleeding Major bleeding

OAC only ASA only OAC+ASA No prophylaxis OAC only ASA only OAC+ASA No prophylaxis
(n=48599) (n=61396) (n=17285) (n=33486) (n=48599) (n=61396) (n=17285) (n=33486)

HAS-BLED ≥ 3 indicates a potentially

0 8919 _ _ _ 0.1 _ _ _ 0.5 “high risk” for bleeding and may
require one of the following:5-6,8-10
1 34944 0.2 0.3 0.4 0.5 0.7 1.1 1.2 2.1 Closer observation of a patient for
adverse risks
2 62140 0.6 0.5 0.6 0.8 1.9 2.1 1.8 3.6 Closer monitoring of INRs in
warfarin-treated patients
Select to Differential dose selections of oral
go back. 3 46417 0.7 0.7 0.9 1.4 2.4 3.1 2.6 5.5 anticoagulants or aspirin
Modification of risk factors
4 15644 1.2 1.2 1.1 1.1 3.4 4.7 3.5 7.8 associated with bleeding
(For example – Hypertension)

5 2069 1.6 1.3 2.8 1.2 5.7 7.0 7.4 9.0 More Information
 Anticoagulation for AFib in Patients Receiving BTK Inhibitors Assess Feasibility for Anticoagulation

The Pathways of Platelet Activation

The illustration demonstrates the pathways of platelet activation and the
Antiplatelet Effects mechanisms of different agents with antiplatelet properties.

Recommendations
Anticoagulant and Antiplatelet Effects
Be cautious about the concurrent use
of BTK Inhibitors
of BTK inhibitors with other
There is an increased risk of antiplatelet agents.
bleeding when combining BTK Avoid concomitant use (if possible)
inhibitors with antiplatelet agents of the following with BTK inhibitors:
and/or anticoagulants. The use of
Non‐steroidal anti‐inflammatory
dual antiplatelet agents and BTK
drugs (NSAIDs)
inhibitors has been associated
Aspirin
with up to >50% increased risk in
Cilostazol
bleeding12 and should be
Clopidogrel
discouraged.
Ticagrelor
Prasugrel
Vorapaxar
Fish oils
ADP: Adenosine diphosphate
Flaxseed
COX: Cycloxygenase Vitamin E
GpIIb/IIIa, GpIa-IIa, GpIb: Glycoprotein (IIb/IIIa, Ia-IIa, Ib) receptors Dipyridamole
TxA2: Thromboxane A2
PAR-1/2: Protease-activated receptor 1/2
PDEIII: Phosphodiesterase III
vWF: Von Willebrand factor
Btk: Bruton’s kinase
Tec: Tyrosine kinase expressed in hepatocellular carcinoma
 Anticoagulation for AFib in Patients Receiving BTK Inhibitors Assess Feasibility for Anticoagulation

Drug Interactions

The risk of thromboembolism is higher in BRAIN

cancer patients, and response to anticoagulation
may not be predictable due to potential drug
interactions with BTK inhibitors or
MOUTH
comorbid conditions.2,11

HEART

STOMACH
LIVER

JOINT

Select each label for guidance on drug interactions.

 Anticoagulation for AFib in Patients Receiving BTK Inhibitors Assess Feasibility for Anticoagulation

Drug Interactions

The risk of thromboembolism is higher in BRAIN

cancer patients, and response to anticoagulation Low Bioavailability:
may not be predictable due to potential drug Ibrutinib-3%
interactions with BTK inhibitors or Acalabrutinib-25%
MOUTH
comorbid conditions.2,11 Zanubrutinib-40%

Tips:
Do not crush or chew tablets/capsules.
Take with or without food.

HEART

STOMACH
LIVER

JOINT
 Anticoagulation for AFib in Patients Receiving BTK Inhibitors Assess Feasibility for Anticoagulation

Drug Interactions

The risk of thromboembolism is higher in BRAIN

cancer patients, and response to anticoagulation
may not be predictable due to potential drug
interactions with BTK inhibitors or
MOUTH
comorbid conditions.2,11

Avoid (if possible) antiplatelet medications,

aspirin, aspirin-containing products, fish oils,
HEART and vitamin E for enhanced antiplatelet
effect and increased bleeding risks.

STOMACH
LIVER

JOINT
 Anticoagulation for AFib in Patients Receiving BTK Inhibitors Assess Feasibility for Anticoagulation

Drug Interactions

The risk of thromboembolism is higher in BRAIN

cancer patients, and response to anticoagulation
may not be predictable due to potential drug
interactions with BTK inhibitors or
MOUTH
comorbid conditions.2,11
Gastric Acid Control:
Ibrutinib and zanubrutinib: Concurrent
PPI and H-2 antagonist acceptable
Acalabrutinib: Avoid co-administration
with PPIs, stagger dosing H-2
antagonists and antacids (either 2
hours before or 2 hours after).

HEART P-gp or BCRA Transport:

Ibrutinib, acalabrutinib, and
zanubrutinib impact substrates.
Medications with a narrow therapeutic
index (e.g., digoxin, dabigatran) may
STOMACH see increases in their plasma
LIVER concentrations.

Tip:
Avoid digoxin or initiate at a lower dose.

JOINT
 Anticoagulation for AFib in Patients Receiving BTK Inhibitors Assess Feasibility for Anticoagulation

Drug Interactions

The risk of thromboembolism is higher in BRAIN

cancer patients, and response to anticoagulation
may not be predictable due to potential drug
interactions with BTK inhibitors or
MOUTH
comorbid conditions.2,11

HEART

Arthralgia Control:
Ibrutinib use with non-selective NSAIDs
STOMACH increases the risk of bleeding and should
LIVER be avoided.

Tip:
Use acetaminophen, opioids, Cox-2
selective NSAIDs (celecoxib, meloxicam),
JOINT and antiepileptics (gabapentin,
pregabalin).
 Anticoagulation for AFib in Patients Receiving BTK Inhibitors Assess Feasibility for Anticoagulation

Drug Interactions
CYP3A Inducers:
Ibrutinib and acalabrutinib: Avoid co-administration
The riskstrong
with of thromboembolism
CYP3A inducers. is higher in
cancer patients,
Zanubrutinib: andco-administration
Avoid response to anticoagulation
with BRAIN
moderate
may not beor strong CYP3A
predictable dueinducers.
to potential drug
interactions with BTK inhibitors or
Tips:
comorbid conditions.2,11 MOUTH
Avoid carbamazepine, rifampicin, and phenytoin.
Dose adjustments may be required.

CYP3A Inhibitors:
Ibrutinib: Dose modifications are required.
(See https://www.accessdata.fda.gov/drugsatfda_docs/
label/2015/205552s002lbl.pdf)
Acalabrutinib: Avoid co-administration with strong
CYP3A inhibitors. Dose modifications are required HEART
with moderate inhibitors.
(See https://www.accessdata.fda.gov/drugsatfda_docs/
label/2017/210259s000lbl.pdf)
Zanubrutinib: Dose modifications are required
with co-administration of strong or moderate
STOMACH
CYP3A inhibitors. LIVER
(See https://www.accessdata.fda.gov/drugsatfda_docs/
label/2019/213217s000lbl.pdf)

Tips:
Avoid HIV antivirals “azole” antifungals, diltiazem,
JOINT
verapamil, amiodarone, and dronedarone.
Either adjust the dose or interrupt the therapy.
Consider β-blockers (atenolol, metoprolol) over
calcium channel blockers (diltiazem, verapamil).
Avoid grapefruit and Seville orange products.
 Anticoagulation for AFib in Patients Receiving BTK Inhibitors Assess Feasibility for Anticoagulation

Drug Interactions

Avoid SSRIs and SNRIs for

The risk of thromboembolism is highereffect
enhanced antiplatelet in BRAIN
cancer patients andand
response
increasedtobleeding
anticoagulation
risks.
may not be predictable due to potential drug
interactions with BTK inhibitors or
MOUTH
comorbid conditions.2,11

HEART

STOMACH
LIVER

JOINT
 Anticoagulation for AFib in Patients Receiving BTK Inhibitors
“What If” Scenarios and Steps
If the patient has AFib and meets these criteria1,12-13
Has low risk for cardioembolic stroke (CHA2DS2-VASc = 0)
Has intermediate risk for cardioembolic stroke (CHA2DS2-VASc = 1)
Uses Ibrutinib; has elevated stroke risk, as per standard models
(CHA2DS2-VASc ≥ 2)
Has aspirin indication + AFib + elevated stroke risk (CHA2DS2-VASc ≥ 2)
Requires DAPT (e.g., those with recent coronary artery stenting) with
AFib and high stroke risk
Has a high bleeding risk or a history of significant bleeding
Implement Anticoagulation
Take this step1,12-13
Continue ibrutinib alone without the addition of anticoagulation or alternative
antiplatelet agents.
Continue ibrutinib alone, or ibrutinib plus aspirin, based on patient-physician
preferences and consideration of individualized risks.
Use a DOAC instead of a vitamin K antagonist without additional antiplatelet agents.
Consider dose adjustment strategies for ibrutinib as follows:
No prior therapy—Initiate dosing of ibrutinib at 420 mg once daily.
Prior therapy without bleeding or bruising—Continue ibrutinib at existing dose.
Therapy with significant bleeding or bruising—Interrupt therapy, reduce dose
by 140 mg per day. Consider a second reduction of dose by 140 mg if needed.
Treat with a DOAC plus ibrutinib alone and stop other antiplatelet agents.
Discontinue ibrutinib due to the significant bleeding risk and switch to
alternative therapy. Manage their AFib as per conventional guidelines.
Consider an alternative agent to ibrutinib and manage their AFib as per conventional
guidelines.
 Anticoagulation for AFib in Patients Receiving BTK Inhibitors Implement Anticoagulation

DOACs Prescriptions
Characteristics of Direct Oral Anticoagulants (DOACs)14

Dabigatran Etexilate Rivaroxaban Apixaban Edoxaban

Target Thrombin Factor Xa Factor Xa Factor Xa

Prodrug Yes No No No

Bioavailability (%) 6.5 80 50 60

Tmax (hours) 1.25-6.0 2-4 1-2.0 1-2.0

Food Effects Delays Tmax Delays Tmax No effect on bioavailability No effect on bioavailability

Half-Life (hours) 12-17 5-9 12 9-11

Renal Excretion (%) 80 65 25 50

Hepatic Biotransformation None 50% (CYP3A4/5, CYP2J2) 25% (CYP3A4/5, CYP1A2, CYP2J2) 10% (CYP3A4)

Coagulation Test TT, dTT, ECT, aPTT Anti-factor Xa assay, PT Anti-factor Xa assay Anti-factor Xa assay

Antidote Idarucizumab Coagulation factor Xa (recombinant), inactivated-zhzo (andexanet)

Interactions P-gp inducers and Combined P-gp and strong CYP3A Combined P-gp and strong P-gp inducers and
inhibitors inhibitors and inducers CYP3A4 inducers and inhibitors inhibitors

aPTT=activated partial thromboplastin time, CYP= Cytochrome P450, dTT= dilute thrombin time, ECT= ecarin clotting time, PAD=Peripheral artery
disease, P-gp= P-glycoprotein, PT=prothrombin time, Tmax = time at which the maximum plasma concentration is observed, TT = thrombin time
Select to view more.
 Anticoagulation for AFib in Patients Receiving BTK Inhibitors Implement Anticoagulation

DOACs Prescriptions
DOACs for Different Parameters11, 15-18

Dabigatran Rivaroxaban Apixaban Edoxaban Enoxaparin

Atrial Fibrillation 150 mg twice daily 20 mg once daily 5 mg twice daily 60 mg once daily 1 mg per kg
(if CrCl 50-95 mL/min) twice daily

Renal Dysfunction
Obesity (BMI ≤ 40 or
Weight ≤ 120 kg)
P-gp Inducers and
CYP3A4 Inducers
75 mg twice daily if CrCl 15 mg once daily if CrCl 2.5 mg twice daily if two of: age ≥80 30 mg once daily if CrCl 1 mg/kg once daily if
15-30 mL/min is < 50mL/min years, serum creatinine ≥1.5 mg/dL or 15-50 mL/min CrCl < 30mL/min
weight ≤60 kg
150 mg twice daily 20 mg once daily 5 mg twice daily 60 mg once daily 1 mg per kg twice daily
(if CrCl 50-95 mL/min) (Anti-Xa monitoring and
dose adjustments are not
necessary for weight <190 kg.)
Avoid concomitant Avoid concomitant Avoid concomitant Avoid concomitant Avoid concomitant
administration. administration. administration. administration. administration.

Reduce dabigatran dose to 75 mg twice No dose reduction No dose reduction No dose reduction No dose reduction
P-gp Inhibitors daily in patients with CrCl 30-50 mL/min
AND receiving dronedarone
or ketoconazole.
Avoid using dabigatran and P-gp
inhibitors with CrCl 15-30mL/min.
Reduce dabigatran dose to 75 mg twice Avoid concomitant For patients receiving 5 mg or 10 mg Avoid concomitant No dose adjustment
Combined P-gp daily in patients with CrCl 30-50 mL/min administration. twice daily, decrease dose by 50%. administration.
and Strong CYP3A4 AND receiving ketoconazole. For patients receiving 2.5 mg twice
Inhibitors Avoid using dabigatran and P-gp daily, avoid coadministration.
inhibitors with CrCl 15-30mL/min.

No dose adjustment Rivaroxaban should not be No dose adjustment No dose adjustment No dose adjustment
Combined P-gp and used in patients with CrCl
Moderate CYP3A4 15 to <80 mL/min.
Inhibitors

Select the blue parameters to view examples.

Select to go back.
 Anticoagulation for AFib in Patients Receiving BTK Inhibitors
DOACs Prescriptions
Atrial Fibrillation
Renal Dysfunction
Obesity (BMI ≤ 40 or
Weight ≤ 120 kg)
P-gp Inducers and
CYP3A4 Inducers
P-gp Inhibitors
Combined P-gp
and Strong CYP3A4
Inhibitors
Combined P-gp and
Moderate CYP3A4
Inhibitors
Select the blue parameters to view examples.
Implement Anticoagulation
DOACs for Different Parameters11, 15-18
Dabigatran Rivaroxaban Apixaban Edoxaban Enoxaparin
150 mg twice daily 20 mg once daily 5 mg twice daily 60 mg once daily 1 mg per kg
(if CrCl 50-95 mL/min) twice daily
75 mg twice daily if CrCl 15 mg once daily if CrCl 2.5 mg twice daily if two of: age ≥80 30 mg once daily if CrCl 1 mg/kg once daily if
15-30 mL/min 15-50 mL/min years, serum creatinine ≥1.5 mg/dL or 15-50 mL/min CrCl < 30mL/min
weight ≤60 kg
150 mg twice daily 20 mg once daily 5 mg twice daily 60 mg once daily 1 mg per kg twice daily
(if CrCl 50-95 mL/min) (Anti-Xa monitoring and
dose adjustments are not
Strong Inducers of P-glycoprotein and CYP3A4 necessary for weight <190 kg.)
Carbamazepine, phenytoin, rifampin, St. John’s
Avoid concomitant Avoid Wort
concomitant Avoid concomitant Avoid concomitant Avoid concomitant
administration. administration. administration. administration. administration.
Reduce dabigatran dose to 75 mg twice No dose reduction No dose reduction No dose reduction No dose reduction
daily in patients with CrCl 30-50 mL/
minute AND receiving dronedarone
or ketoconazole.
Avoid using dabigatran and P-gp
inhibitors with CrCl 15-30mL/minute.
Reduce dabigatran dose to 75 mg twice Avoid concomitant For patients receiving 5 mg or 10 mg Avoid concomitant No dose reduction
daily in patients with CrCl 30-50 mL/ administration. twice daily, decrease dose by 50%. administration.
minute AND receiving ketoconazole. For patients receiving 2.5 mg twice
Avoid using dabigatran and P-gp daily, avoid coadministration.
inhibitors with CrCl 15-30mL/minute.
No dose reduction Rivaroxaban should not be No dose reduction No dose reduction No dose reduction
used in patients with CrCl
15 to <80 mL/min.
Select to go back.
 Anticoagulation for AFib in Patients Receiving BTK Inhibitors
DOACs Prescriptions
Atrial Fibrillation
Renal Dysfunction
Obesity (BMI ≤ 40 or
Weight ≤ 120 kg)
P-gp Inducers and
CYP3A4 Inducers
P-gp Inhibitors
Combined P-gp
and Strong CYP3A4
Inhibitors
Combined P-gp and
Moderate CYP3A4
Inhibitors
Select the blue parameters to view examples.
Implement Anticoagulation
DOACs for Different Parameters11, 15-18
Dabigatran Rivaroxaban Apixaban Edoxaban Enoxaparin
150 mg twice daily 20 mg once daily 5 mg twice daily 60 mg once daily 1 mg per kg
(if CrCl 50-95 mL/min) twice daily
75 mg twice daily if CrCl 15 mg once daily if CrCl 2.5 mg twice daily if two of: age ≥80 30 mg once daily if CrCl 1 mg/kg once daily if
15-30 mL/min 15-50 mL/min years, serum creatinine ≥1.5 mg/dL or 15-50 mL/min CrCl < 30mL/min
weight ≤60 kg
150 mg twice daily 20 mg once daily 5 mg twice daily 60 mg once daily 1 mg per kg twice daily
(if CrCl 50-95 mL/min) (Anti-Xa monitoring and
dose adjustments are not
necessary for weight <190 kg.)
Avoid concomitant Avoid concomitant Avoid concomitant Avoid concomitant Avoid concomitant
administration. administration. administration. administration. administration.
P-gp Inhibitors
Reduce dabigatran dose to 75 mg twice No dose reduction No dose reduction No dose reduction No dose reduction
Amiodarone, clarithromycin, dronedarone,
daily in patients with CrCl 30-50 mL/
ketoconazole,
minute AND quinidine, ticagrelor, verapamil
receiving dronedarone
or ketoconazole.
Avoid using dabigatran and P-gp
inhibitors with CrCl 15-30mL/minute.
Reduce dabigatran dose to 75 mg twice Avoid concomitant For patients receiving 5 mg or 10 mg Avoid concomitant No dose reduction
daily in patients with CrCl 30-50 mL/ administration. twice daily, decrease dose by 50%. administration.
minute AND receiving ketoconazole. For patients receiving 2.5 mg twice
Avoid using dabigatran and P-gp daily, avoid coadministration.
inhibitors with CrCl 15-30mL/minute.
No dose reduction Rivaroxaban should not be No dose reduction No dose reduction No dose reduction
used in patients with CrCl
15 to <80 mL/min.
Select to go back.
 Anticoagulation for AFib in Patients Receiving BTK Inhibitors
DOACs Prescriptions
Atrial Fibrillation
Renal Dysfunction
Obesity (BMI ≤ 40 or
Weight ≤ 120 kg)
P-gp Inducers and
CYP3A4 Inducers
P-gp Inhibitors
Combined P-gp
and Strong CYP3A4
Inhibitors
Combined P-gp and
Moderate CYP3A4
Inhibitors
Select the blue parameters to view examples.
Implement Anticoagulation
DOACs for Different Parameters11, 15-18
Dabigatran Rivaroxaban Apixaban Edoxaban Enoxaparin
150 mg twice daily 20 mg once daily 5 mg twice daily 60 mg once daily 1 mg per kg
(if CrCl 50-95 mL/min) twice daily
75 mg twice daily if CrCl 15 mg once daily if CrCl 2.5 mg twice daily if two of: age ≥80 30 mg once daily if CrCl 1 mg/kg once daily if
15-30 mL/min 15-50 mL/min years, serum creatinine ≥1.5 mg/dL or 15-50 mL/min CrCl < 30mL/min
weight ≤60 kg
150 mg twice daily 20 mg once daily 5 mg twice daily 60 mg once daily 1 mg per kg twice daily
(if CrCl 50-95 mL/min) (Anti-Xa monitoring and
dose adjustments are not
necessary for weight <190 kg.)
Avoid concomitant Avoid concomitant Avoid concomitant Avoid concomitant Avoid concomitant
administration. administration. administration. administration. administration.
Reduce dabigatran dose to 75 mg twice No dose reduction No dose reduction No dose reduction No dose reduction
daily in patients with CrCl 30-50 mL/
minute AND receiving dronedarone
or ketoconazole.
Avoid using dabigatran and P-gp
inhibitors with CrCl 15-30mL/minute.
Reduce dabigatran
Combined P-gp anddose to 75
Strong mg twiceInhibitors
CYP3A4 Avoid concomitant For patients receiving 5 mg or 10 mg Avoid concomitant No dose reduction
daily in patients with CrCl 30-50 mL/ administration. twice daily, decrease dose by 50%. administration.
Clarithromycin, itraconazole,
minute AND receiving ketoconazole, ritonavir
ketoconazole. For patients receiving 2.5 mg twice
Avoid using dabigatran and P-gp daily, avoid coadministration.
inhibitors with CrCl 15-30mL/minute.
No dose reduction Rivaroxaban should not be No dose reduction No dose reduction No dose reduction
used in patients with CrCl
15 to <80 mL/min.
Select to go back.
 Anticoagulation for AFib in Patients Receiving BTK Inhibitors
DOACs Prescriptions
Atrial Fibrillation
Renal Dysfunction
Obesity (BMI ≤ 40 or
Weight ≤ 120 kg)
P-gp Inducers and
CYP3A4 Inducers
P-gp Inhibitors
Combined P-gp
and Strong CYP3A4
Inhibitors
Combined P-gp and
Moderate CYP3A4
Inhibitors
Select the blue parameters to view examples.
Implement Anticoagulation
DOACs for Different Parameters11, 15-18
Dabigatran Rivaroxaban Apixaban Edoxaban Enoxaparin
150 mg twice daily 20 mg once daily 5 mg twice daily 60 mg once daily 1 mg per kg
(if CrCl 50-95 mL/min) twice daily
75 mg twice daily if CrCl 15 mg once daily if CrCl 2.5 mg twice daily if two of: age ≥80 30 mg once daily if CrCl 1 mg/kg once daily if
15-30 mL/min 15-50 mL/min years, serum creatinine ≥1.5 mg/dL or 15-50 mL/min CrCl < 30mL/min
weight ≤60 kg
150 mg twice daily 20 mg once daily 5 mg twice daily 60 mg once daily 1 mg per kg twice daily
(if CrCl 50-95 mL/min) (Anti-Xa monitoring and
dose adjustments are not
necessary for weight <190 kg.)
Avoid concomitant Avoid concomitant Avoid concomitant Avoid concomitant Avoid concomitant
administration. administration. administration. administration. administration.
Reduce dabigatran dose to 75 mg twice No dose reduction No dose reduction No dose reduction No dose reduction
daily in patients with CrCl 30-50 mL/
minute AND receiving dronedarone
or ketoconazole.
Avoid using dabigatran and P-gp
inhibitors with CrCl 15-30mL/minute.
Reduce dabigatran dose to 75 mg twice Avoid concomitant For patients receiving 5 mg or 10 mg Avoid concomitant No dose reduction
daily in patients with CrCl 30-50 mL/ administration. twice daily, decrease dose by 50%. administration.
minute AND receiving ketoconazole. For patients receiving 2.5 mg twice
Avoid using dabigatran and P-gp daily, avoid coadministration.
inhibitors with CrCl 15-30mL/minute.
Combined P-gp and Moderate CYP3A4 Inhibitors
No dose reduction Rivaroxaban should not be No dose reduction No dose reduction No dose reduction
Erythromycin, fluconazole used in patients with CrCl
15 to <80 mL/min.
Select to go back.
 Anticoagulation for AFib in Patients Receiving BTK Inhibitors References

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