Which patients may benefit from extended anticoagulation?

Click here to view ELIQUIS® (apixaban) prescribing and adverse event reporting information.

Watch the video below for a discussion by Dr Ander Cohen on the evaluation of the risk of VTE recurrence.

The risk of VTE recurrence after cessation of anticoagulant varies according to the features of the index DVT or PE.^1-3 Other risk factors (e.g. proximal vs. distal location and male vs. female sex) contribute to the risk.^2,3

Of note, VTE recurrence is higher in those with unprovoked (i.e., idiopathic) VTE than those with provoked VTE (i.e., VTE associated with a transient major clinical risk factor).^4,5 A UK study including 35,373 first VTE events revealed 28.4% of those with unprovoked VTE had a risk of a recurrent event within 10 years, compared with 20.5% of those with provoked VTE.⁴

VTE recurrence is higher in unprovoked VTE.⁴

Adapted from Martinez et al. 2014.⁴
* E.g. surgery, trauma, significant immobility (bedbound, unable to walk unaided or likely to spend a substantial proportion of day in bed or in a chair), pregnancy or puerperium.⁵ Avoid the use of apixaban in pregnancy and breastfeeding.⁶
† Oral contraceptive or hormone replacement therapy.⁵

Patients with VTE (without cancer) who are receiving an anticoagulant should have a review within 3 months to discuss the risks and benefits of continuing anticoagulation therapy.⁷ Patients may have had their treatment initiated while in hospital but may be discharged from secondary care before their treatment is complete. GPs therefore play an important role in the long-term management of patients with VTE.

The key primary estimator of recurrence in patients with VTE who stop anticoagulation is unprovoked VTE. Such patients have approximately 10% and 30% risk of experiencing a recurrent VTE event at 1 and 5 years, respectively.⁸

Recent research shows that recurrence rates in patients with VTE provoked by minor persistent or minor transient risk factors are equivalent to those with unprovoked VTE. Therefore, such patients may also benefit from extended anticoagulation therapy.⁹

NICE NG158: Long-term anticoagulation for secondary prevention⁵

Watch the video below for a discussion by Dr Ander Cohen on the updated 2020 NICE guideline recommendations for the use of DOACs for the long-term treatment of appropriate patients with confirmed DVT or PE.

NICE NG158 recommends considering stopping anticoagulation 3 months^‡ after a provoked DVT / PE, if the provoking factor is no longer present and the clinical course has been uncomplicated. Provoked DVT or PE is defined as:⁵

DVT or PE in a person with a recent (within 3 months) and transient major clinical risk factor for VTE, such as surgery, trauma, significant immobility (bedbound, unable to walk unaided or likely to spend a substantial proportion of the day in bed or in a chair), pregnancy or puerperium – or in a person who is having hormonal therapy (combined oral contraceptive or HRT)

NICE NG158 recommends considering continuing anticoagulation beyond 3 months^§ after an unprovoked DVT / PE, basing the decision on the balance between the person’s risk of venous thromboembolism (VTE) recurrence and their risk of bleeding. Unprovoked is defined as:⁵

DVT or PE in a person with no recent major clinical risk factor for VTE (see provoked DVT or PE) who is not having hormonal therapy (combined oral contraceptive pill or HRT)

For people who do not have renal impairment, active cancer, established triple positive antiphospholipid syndrome or extreme body weight (less than 50 kg or more than 120 kg), NICE NG158 recommends the following:⁵

offer continued treatment with the current anticoagulant if it is well tolerated or
if the current treatment is not well tolerated, or the clinical situation or person’s preferences have changed, consider switching to apixaban if the current treatment is a direct-acting anticoagulant other than apixaban

For people with renal impairment, active cancer, established triple positive antiphospholipid syndrome or extreme body weight (less than 50 kg or more than 120 kg), consider carrying on with the current treatment if it is well tolerated.⁵

‡ NICE NG158: 3–6 months for people with active cancer.⁵
§ NICE NG158: 6 months for people with active cancer.⁵
See full guidance for further details.

-NICE NG158, 2020⁵

Not all patients who start on apixaban for acute DVT / PE will stay on apixaban; some acute DVT / PE patients who receive treatment do not require treatment for the prevention of recurrent DVT / PE. Other patients may be prescribed apixaban for the prevention of recurrent DVT after initial treatment for acute DVT / PE with another anticoagulant.⁶ This is an assessment for the prescribing clinician together with patient involvement.
Apixaban should be used with caution in patients with severe renal impairment (CrCl 15–29 ml/min) for the treatment of DVT or PE and prevention of recurrent DVT or PE.⁶
Apixaban is not recommended in patients with CrCl <15 ml/min, or in patients undergoing dialysis.⁶
Patients with active cancer can be at high risk of both venous thromboembolism and bleeding events. When apixaban is considered for DVT or PE treatment in cancer patients, a careful assessment of the benefits against the risks should be made.⁶
Apixaban is not recommended in patients with a history of thrombosis who are diagnosed with antiphospholipid syndrome.⁶

Determining the duration of extended anticoagulation

A short duration of treatment (at least 3 months) should be based on transient risk factors (e.g., recent surgery, trauma, or immobilisation).^1,2 The duration of overall therapy should be individualised after careful assessment of the treatment benefit against the risk for bleeding.⁵

Clinical prediction tools are available to help determine the risk of recurrent VTE²

These include:

DASH, which uses D-Dimer levels, Age, Sex and Hormone use in women to predict the likelihood of recurrent VTE,² and is accessible via this link
HERDOO2, which is used in women with unprovoked VTE and assesses post-thrombotic signs, D-dimer levels, BMI and Age to determine the risk of recurrent VTE, and is accessible via this link
The Vienna prediction tool, which uses sex, location of VTE and D-dimer levels²to determine the risk of recurrent VTE, accessible via this link

It is important not to rely solely on predictive risk tools to assess the need for long-term anticoagulation treatment.

Please note that the BMS / Pfizer Alliance are not responsible for the accuracy of these assessment tools.

Patient involvement

The decision to stop or continue anticoagulation should always include patient involvement.⁵ As described by NICE quality standards for patient experience, patients should be supported by healthcare professionals to understand relevant treatment options, including benefits, risks, potential consequences and be actively involved in shared decision-making.¹⁰

Adverse events should be reported. Reporting forms and information can be found via United Kingdom – The yellow card scheme at www.mhra.gov.uk/yellowcard, or search for MHRA Yellow Card in the Google Play or Apple App Store. Adverse events should also be reported to Bristol-Myers Squibb via medical.information@bms.com or 0800 731 1736 (United Kingdom).

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In Preventing VTE recurrence: Preventing recurrence | Which patients may benefit from extended anticoagulation? | Evidence in long-term prevention of VTE recurrence |

Abbreviations

BMI=Body Mass Index CPRD=Clinical Practice Research Datalink DOAC=Direct-acting Oral Anticoagulant DVT=Deep Vein Thrombosis HRT=Hormone Replacement Therapy MHRA=Medicines and Healthcare products and Regulatory Agency NICE=National Institute for Health and Care Excellence OAC=Oral Anticoagulant PE=Pulmonary Embolism VTE=Venous Thromboembolism

References

Konstantinides SV et al. Eur Heart J 2020; 41: 543–603.
Mazzolai L et al. Eur Heart J 2018; 39: 4208–4218.
Fahrni J et al. Vasc Health Risk Manag 2015; 11: 451–459.
Martinez C et al. Thromb Haem 2014; 112: 255–263.
Venous thromboembolic diseases: diagnosis, management and thrombophilia testing [NG158]. 26 March 2020.
Apixaban Summary of Product Characteristics. Available at: www.medicines.org.uk/emc/search?q=apixaban.
Quality Standard [QS29]. Venous thromboembolism in adults: diagnosis and management.
Kearon C & Akl EA. Blood 2014; 123: 1794–1801.
Prins MH et al. Blood Adv 2018; 2: 788–796.
NICE Quality Standard [QS15]. Patient experience in adult NHS services.