Guideline on Anticoagulation Options for Patients with Atrial Fibrillation Undergoing Systemic Anti-Cancer Therapy (SACT)

Publication: 26/11/2019  --
Last review: 01/01/1900  
Next review: 26/11/2022  
Clinical Guideline
CURRENT 
ID: 6247 
Approved By: Trust Clinical Guidelines Group 
Copyright© Leeds Teaching Hospitals NHS Trust 2019  

 

This Clinical Guideline is intended for use by healthcare professionals within Leeds unless otherwise stated.
For healthcare professionals in other trusts, please ensure that you consult relevant local and national guidance.

Guideline on Anticoagulation Options for Patients with Atrial Fibrillation Undergoing Systemic Anti-Cancer Therapy (SACT)

Summary of Guideline

This guideline gives advice to oncologists and haematologists regarding patients on anticoagulation for stroke prevention due to Atrial Fibrillation (AF). It will help them to decide on the options for anticoagulation while the patient undergoes systemic anti-cancer therapy (SACT). It covers interactions, stroke risk and anticoagulant options including when anticoagulation should be stopped or withheld due to bleeding risk, decline in renal function or thrombocytopenia.

Aims

To give advice and guidance on the management of  anticoagulation for AF patients undergoing SACT
Patients with metallic valves, VTE or other reasons for anticoagulation are beyond the scope of this guideline

Objectives

To provide evidence-based or expert consensus recommendations for appropriate management of anticoagulation in patients with AF undergoing SACT

Background

A greater number of patients are now being anticoagulated to reduce their risk of stroke due to AF. Some of these patients may be diagnosed with cancer and require SACT. A lot is known about the safety of low molecular heparin (LMWH) in patients undergoing chemotherapy (but less is known about it to reduce stroke risk in patients with AF) but less is known about the direct oral anticoagulants (DOACs), apixaban, edoxaban, dabigatran and rivaroxaban. There are no specific trials in this population and very few cancer patients on active treatment in the trials. Data is based on limited evidence and trials in cancer associated thrombosis. Though a lot is known about warfarin this is often very difficult to manage in patients undergoing chemotherapy due to interactions, diet changes, nausea and vomiting etc.

Diagnosis

All patients with AF undergoing SACT should have a ChadsVasc score calculated to understand the stroke risk. https://www.mdcalc.com/cha2ds2-vasc-score-atrial-fibrillation-stroke-risk

Investigation

All patients need baseline U&E, LFTs, FBC and a clotting screen. The DOACs do not all affect the clotting screen in normal doses. A raised prothrombin time and therefore INR is often seen with rivaroxaban and to a lesser extent with edoxaban. INR values < 2.5 are frequently seen with rivaroxaban and < 1.8 with edoxaban. Dabigatran causes a raised APTT. Clotting screens can be affected if the drug accumulates, in renal impairment, when combined with drugs which are enzyme inhibitors or in overdose. A baseline is helpful to monitor a patient through their treatment. The time of the clotting screen in relation to the time of the last dose of the DOAC should be recorded.

Treatment / Management

Low Risk of stroke CHA2DS2-VASc score of 0 to 1 - Anticoagulation can be discontinued while undergoing SACT.
CHA2DS2-VASc score 2 or more - anticoagulation should be continued in these patients
If uncertainty or complicated patient in respect to their cardiology history discuss with cardiology
If concerns regarding bleeding risk discuss with haematology.

Options for anticoagulation include LMWH or DOACs. Warfarin should be avoided unless it is known that the SACT will not interact, the regime is not emetogenic and the patient can attend for frequent INR tests.

The following patients on warfarin for AF should remain on warfarin or be switched to LMWH (this group should not be switched to a DOAC)
certain interactions - see below,
any patient with a metallic valve
patients at extremes of weight <50kg, >120kg,
poor renal function (creatinine clearance <30mls/minute),
liver dysfunction, (LFTs 2 x upper limit of normal or Childs Pugh B or C)

Patients having traditional cytotoxic chemotherapy who need to continue anticoagulation should have the benefits and risks of DOACs vs LMWH discussed including lack of antidote for some DOACs, higher bleeding rates seen in cancer associated thrombosis trials, side effects, risk of thrombocytopenia, interactions and variable absorption due to potential nausea and vomiting.
 
Criteria for DOAC use in cancer patients requiring anticoagulation
Patient assessment

Risk factors for bleeding precluding DOAC use
Recent bleeding events in the past 2 months including patients with active GI mucosal abnormalities
Intracranial or visceral tumor, renal cell carcinoma or metastatic melanoma at high risk for major bleeding
Luminal gastrointestinal cancer with an intact primary
Cancer at risk of bleeding in genitourinary tract, bladder or nephrostomy tubes

Platelets
Platelet count >50,000 per mL and no anticipated decrease due to disease or SACT

Coagulation studies
Normal PT, APTT, and fibrinogen - note information above on DOACs and effect on PT and APTT test

Liver function tests
No significant hepatic impairment (e.g. No Child-Pugh B or C, no cirrhosis, LFTs not above 2 x upper limit of normal)

Renal function
CrCl >30 mL/min (apixaban, edoxaban, rivaroxaban)
CrCl >50 mL/min (dabigatran)
No anticipated fluctuations due to nephrotoxic chemotherapy or other drugs

Medications
No concomitant use of drugs with strong effect on CYP3A4 and/ or P-glycoprotein - see later

Good medication compliance

If there are issues highlighted from the list above, LMWH should be used if anticoagulation is required.

Interactions
When considering using a DOAC or if the patient is already on a DOAC and it is thought to be appropriate to continue, please use the interaction checker developed by University of Liverpool to assess if possible interactions with SACT or supportive care

https://cancer-druginteractions.org/

If interactions are a problem, the  “view all checker” can be used which lists all drugs by BNF class (select “Anti-coagulant, Anti-platelet and Fibrinolytic” in this case) and may suggest safer alternatives. Switching a DOAC may be an option such as apixaban/rivaroxaban to edoxaban or edoxaban/dabigatran to apixaban/rivaroxaban 

If the drugs concerned are not listed, please discuss with Pharmacy.

There are a number of interactions of DOACs with non-SACT treatments including:

  • HIV protease inhibitors
  • azole antifungals except fluconazole,
  • rifampicin,
  • carbamazepine, phenytoin, phenobarbitone, primidone

which may be prescribed in this patient group and may require LMWH instead of a DOAC.

*Dexamethasone may affect DOAC levels as it is a moderate inducer of CYP3A4 and P-glycoprotein. Patients can remain on DOACs but should be monitored closely. Note no issues were seen in the cancer associated thrombosis trials when dexamethasone was combined with DOACs

DOAC specific information
Dabigatran is the only DOAC to have a specific antidote but is 85% renally excreted so should be avoided in patients with creatinine clearance < 50ml/min or with SACT that is expected to reduce renal function. In these cases, consider switching to apixaban, edoxaban or rivaroxaban prior to commencing SACT

Rivaroxaban must be taken with a meal for absorption. If this is likely to be problematic, consider switching to an alternative DOAC.

Rivaroxaban, edoxaban and apixaban can be crushed and taken with fluid or apple puree or put down a feeding tube. Take care with rivaroxaban as this must be given when there is food in the stomach for absorption. Consider an alternative DOAC if this is likely to be problematic.

During treatment
Changes to baseline tests
Raised LFTs to > 2 times upper limit of normal - switch to LMWH until normalised

Platelets <50,000 per mL withhold DOAC/LMWH until >50,000 per mL

If a patient develops an acute venous thromboembolism while on a DOAC, switch to LMWH

Drug levels may be appropriate for patients staying on a DOAC when there is a lack of information or weak interactions. Discuss with Pharmacy

Abbreviations: CrCl, creatinine clearance; PT, prothrombin time; APTT, activated partial thromboplastin time.

Provenance

Record: 6247
Objective:

To provide evidence-based or expert consensus recommendations for appropriate management of anticoagulation in patients with AF undergoing SACT

Clinical condition:

AF and cancer

Target patient group: Patients anticoagulated for AF requiring SACT
Target professional group(s): Pharmacists
Secondary Care Doctors
Adapted from:

Evidence base

References  and Evidence levels:

  1. Comparative effectiveness of direct oral anticoagulants and warfarin in patients with cancer and atrial fibrillation. Blood Adv. 2018 Feb 13;2(3):200-209. doi: 10.1182/bloodadvances.2017010694. Shah S1, Norby FL2, Datta YH1, Lutsey PL2, MacLehose RF2, Chen LY1, Alonso A3.
  2. Role of direct oral anticoagulants in the treatment of cancer‐associated venous thromboembolism: guidance from the SSC of the ISTH
    A. A. Khorana et al. First published: 29 June 2018https://doi.org/10.1111/jth.14219

Approved By

Trust Clinical Guidelines Group

Document history

LHP version 1.0

Related information

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