Before starting

Required

• Baseline
  • Baseline clotting screening
  • Body weight
  • Full blood count
  • Liver function tests
  • Serum creatinine (for creatinine clearance)
  • Urea and electrolytes

Monitoring renal function

Cockcroft and Gault is recommended for calculating creatinine clearance for DOACs. Estimated glomerular filtration rate can overestimate renal function and increase risk of bleeding events.

Consider

• Baseline
  • Blood pressure · for calculation of HAS-BLED score if required

After started or dose changed

Required

• After 1 month
  • DOAC review appointment

Ongoing once stable

Required

• Every 3 months
  • DOAC review appointment
• Annually; more frequently if clinical concerns
  • Full blood count
  • Liver function tests
  • Urea and electrolytes
  • Serum creatinine (for creatinine clearance)

When to consider more frequent monitoring

Concomitant medicines are prescribed

Consider a change in testing frequency if concomitant medicines are prescribed which may affect renal or hepatic function.

Elderly

Monitoring every 4 months is normally most appropriate.

Hepatic function changes

Intercurrent illness occurs

Renal function changes

If renal function changes, increase monitoring frequency.
Where a patient shows a creatinine clearance of below 60mL/min, divide the value by 10, and use the value obtained as the monthly testing frequency. E.g. if CrCl is 30mL/min, increase frequency to every 3 months; if CrCl is 20mL/min, increase frequency to every 2 months.

Abnormal results

Responding to abnormal results for DOACs is dependent on the individual medicine prescribed.

Apixaban

Renal function

Take action if creatinine or creatinine clearance abnormal:

• If CrCL less than 15mL/min: avoid apixaban; assess for bleeding or anaemia; seek advice regarding alternative anticoagulant therapy.
• If CrCL 15-29mL/min and apixaban prescribed for prevention of recurrent DVT, PE, and treatment of DVT or PE, then continue with caution.
• If CrCL 15-29mL/min and apixaban prescribed for prophylaxis of stroke and systemic embolism in a person with NVAF, reduce dose to 2.5mg twice daily.

Reduce dose for old age, low body weight, high creatinine

Use 2.5 mg twice daily if NVAF and two or more of:

• age ≥ 80 years
• body weight ≤ 60 kg
• serum creatinine ≥ 1.5 mg/dL (133 micromol/L)

Decreased haemoglobin or bleeding

If there is an unexplained fall in haemoglobin or haematocrit, occult bleeding may be present (apixaban can cause bleeding from any site). Stop treatment and seek specialist advice.

Hepatic impairment

Use with caution in mild or moderate hepatic impairment:

• Child Pugh A or B.
• ALT/ AST over 2 times the upper limit of normal.
• Total bilirubin over 1.5 times the upper limit of normal.

Avoid apixaban in:

• Severe impairment.
• Hepatic disease associated with coagulopathy and clinically relevant bleeding risk.

HAS-BLED

If the patient’s HAS-BLED score is more than 3, there is high risk of bleeding and apixaban should be used cautiously, with regular reviews.

Dabigatran

Renal function

Take action if creatinine clearance abnormal:

• CrCL less than 30mL/min: avoid dabigatran.
• CrCL 30-50mL/min: a reduction in dose may be required, consult product literature.

Hepatic function

Use with caution in:

• Mild to moderate impairment.
• ALT/ AST over 2 times the upper limit of normal.
• Total bilirubin over 1.5 times the upper limit of normal.

Avoid in:

• Severe impairment.
• Hepatic disease associated with coagulopathy and clinically relevant bleeding risk.

Reduce dose in elderly or if verapamil prescribed

If the patient is elderly or taking concomitant verapamil, consult product literature for advice on dose reduction.

Edoxaban

Renal function

Take action if creatinine clearance abnormal:

• CrCL less than 15mL/min: edoxaban is contraindicated. Assess for bleeding or anaemia and seek advice regarding alternative anticoagulant therapy.
• CrCL 15-50mL/min: reduce dose to 30mg once daily.
• CrCL over 80mL/min: re-evaluate treatment choice and consider alternative. A trend towards decreasing efficacy with increasing creatinine clearance has been observed compared to well managed warfarin. Edoxaban should only be used in some indications after a careful evaluation of the individual thromboembolic and bleeding risk.

Hepatic function

Use with caution in:

• Mild to moderate impairment.
• ALT/ AST over 2 times the upper limit of normal.
• Total bilirubin over 1.5 times the upper limit of normal.

Avoid in:

• Severe impairment.
• Hepatic disease associated with coagulopathy and clinically relevant bleeding risk.

HAS-BLED

If the person’s HAS-BLED score is more than 3, there is high risk of bleeding and edoxaban should be used cautiously, with regular reviewss.

Rivaroxaban

Renal function

Take action if creatinine clearance abnormal:

• CrCL less than 15mL/min: avoid rivaroxaban.
• CrCL 15-49mL/min: consult product literature for indication specific advice.

Hepatic impairment

Manufacturer advises avoid in hepatic disease with coagulopathy and clinically-relevant bleeding risk including patients with moderate to severe cirrhosis.

Bleeding

Patients should be monitored for signs of bleeding or anaemia; treatment should be stopped if severe bleeding occurs.

Notes

What to assess at a review appointment

No routine anticoagulation monitoring is needed for DOACs; however, conduct review appointments regularly at which you should:

• Assess adherence to treatment.
• Look for signs of bleeding or anaemia.
• Ask about other adverse effects of DOAC.
• Assess for features of thromboembolic events, such as symptoms of stroke, or breathlessness (which may suggest a pulmonary embolism).
• Ask about the use of other medications, including over-the-counter (OTC) products, to identify possible drug interactions with DOAC.
• Assess and minimise modifiable risk factors for bleeding, such as uncontrolled hypertension, medication predisposing for bleeding (such as aspirin), and excessive alcohol intake.
• Give appropriate information and advice on DOAC treatment.

Bibliography

• Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press [cited 30/06/2020]
• Bristol-Myers Squibb-Pfizer. Summary of Product Characteristics -Eliquis 5 mg film-coated tablets. Last revised 01/2020 [cited 30/07/2020]
• Boehringer Ingelheim Limited. Summary of Product Characteristics – Pradaxa 150 mg hard capsules. Last revised 07/2020 [cited 19/08/2020]
• Daiichi Sankyo Europe GmbH. Summary of Product Characteristics – Lixiana 30mg Film-Coated Tablets. Last revised 09/2019 [cited 17/01/2020]
• Bayer plc. Summary of Product Characteristics – Xarelto 20mg film-coated tablets. Last revised 11/2019 [cited 17/08/2020]
• NICE Clinical Knowledge Summaries (CKS). Anticoagulation – oral. Updated Jun 2019 [cited 04/02/2020]
• Steffel J, Collins R, Antz M, Cornu P et al.  2021 European Heart Rhythm Association Practical Guide on the Use of Non-Vitamin K Antagonist Oral Anticoagulants in Patients with Atrial Fibrillation. Europace (2021) 23, 1612–1676 doi:10.1093/europace/euab065 [cited 03/05/2022]
• Medicines and Healthcare products Regulatory Agency. Prescribing medicines in renal impairment: using the appropriate estimate of renal function to avoid the risk of adverse drug reactions. Drug Safety Update volume 13, issue 3: October 2019: 3. [cited 13/02/2000]
• MHRA Drug Safety Update.  Direct-acting oral anticoagulants (DOACs): reminder of bleeding risk, including availability of reversal agents (June 2020) [cited 28/04/2022]
• GP notebook. HAS-BLED score for bleeding risk on oral anticoagulation in atrial fibrillation (AF) [cited 18/08/2016]
• The Handbook of Perioperative Medicines UKCPA. Medicine monographs. Direct oral anticoagulants (DOACS): Apixaban, Dabigatran, Edoxaban, Rivaroxaban. [Cited 30/07/2020]
• U.S Food & Drug Administration. Highlights of prescribing information – SAVAYSA (edoxaban) tablets, for oral use. Initial U.S. Approval: 2015. Reference ID: 4474918 [cited 23/01/2020]

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