Initial management of a confirmed VTE
Click here to view ELIQUIS® (apixaban) prescribing and adverse event reporting information.
Patients with DVT / PE should be offered treatment with an anticoagulant.1 Conventional treatment consists of a parenteral anticoagulant, such as enoxaparin, for at least 5 days given concurrently with warfarin, followed by warfarin for at least 3 months.2 However, four DOACs3-6, apixaban, dabigatran, edoxaban and rivaroxaban, have been approved for the treatment of DVT / PE and the prevention of recurrent DVT / PE in adults. Dabigatran and edoxaban should be administered following initial use of parenteral anticoagulant for at least 5 days.4,5 The DOACs are recommended, within their marketing authorisations, as first line by NICE7-12 and have been accepted for use by the Scottish Medicines Consortium (SMC).13-16
NICE treatment guidelines for confirmed DVT or PE
Offer either apixaban or rivaroxaban to people with confirmed proximal DVT or PE (but see recommendations for people with any of the clinical features listed in 1.3.7).1*
If neither apixaban nor rivaroxaban is suitable offer:1
- low molecular weight heparin (LMWH) for at least 5 days followed by dabigatran or edoxaban or
- LMWH concurrently with a vitamin K antagonist (VKA) for at least 5 days, or until the INR is at least 2.0 in 2 consecutive readings, followed by a VKA on its own.1
* NICE NG158: When offering anticoagulation treatment, take into account comorbidities, contraindications and the person’s preferences. Clinical features listed in 1.3.7.1
- DVT or PE in people at extreme body weight
- PE with haemodynamic instability
- DVT or PE with renal impairment or established renal failure*
- DVT or PE with active cancer†
- DVT or PE with triple antiphospholipid syndrome‡
See full guidance for further details.
-NICE NG158, 2020
Outpatient treatment
Consider outpatient treatment for suspected or confirmed low-risk PE, using a validated risk stratification tool to determine the suitability of outpatient treatment. When offering outpatient treatment to people with suspected PE, follow the NICE recommendations 1.1.15 to 1.1.21 on diagnosis and initial management.1
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 initial treatment of appropriate patients with confirmed DVT or PE.
NICE NG158 recommends apixaban as an option for the treatment of DVT or PE1
NICE NG158: Anticoagulation treatment for confirmed DVT or PE1
1.3.5: For people with confirmed proximal DVT or PE, offer anticoagulation treatment for at least 3 months
1.3.7: When offering anticoagulation treatment for confirmed proximal DVT or PE, take into account comorbidities, contraindications and the person’s preferences
1.3.8: Offer either apixaban or rivaroxaban to people with confirmed proximal DVT or PE unless they have one of the comorbidities listed below:
- PE with haemodynamic instability, DVT or PE with renal impairment (CrCl 15–50 ml/min) or established renal failure (CrCl <15 ml/min),* DVT or PE with extreme body weight (weighing <50 kg or >120 kg), DVT or PE with active cancer,† DVT or PE with triple positive antiphospholipid syndrome‡
Adapted from NICE NG158.
1 See
full guidance for further details.
Duration of therapy should be individualised after careful assessment of the treatment benefit against the risk for bleeding.
1,3
The decision to stop or continue anticoagulation should always include patient involvement.
17
* 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.
3 Apixaban is not recommended in patients with CrCl <15 ml/min, or in patients undergoing dialysis.
3
† 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.
3
‡ Apixaban is not recommended in patients with a history of thrombosis who are diagnosed with antiphospholipid syndrome.
3
In the AMPLIFY clinical trial, at 6 months apixaban demonstrated:2
- comparable efficacy for rates of recurrent VTE / VTE-related death vs. enoxaparin / warfarin
- significant reductions in rates of both major and major / CRNM bleeding vs. enoxaparin / warfarin
Adapted from Agnelli et al. 20132 and the ELIQUIS smPC.3
The AMPLIFY RCT randomised 5,395 patients with confirmed, symptomatic DVT / PE to treatment with apixaban 10 mg twice daily for 7 days, followed by apixaban 5 mg twice daily orally for 6 months, or enoxaparin / warfarin for 6 months.2
* The primary efficacy endpoint was recurrent symptomatic VTE or VTE-related death.2
† The primary safety endpoint was major bleeding and the secondary safety endpoint was a composite of major and CRNM bleeding.2 For patients who had more than one event, only the first was counted.2 Efficacy analyses were based on ITT population for whom the outcome status at 6 months was documented. All safety analyses included data obtained from patients during study treatment, defined as the time from administration of the first dose until 48 hours after the last dose was administered.2
Apixaban dosing regimen3
* As per available medical guidelines, short duration of treatment (at least 3 months) should be based on transient risk factors, (e.g. recent surgery, trauma, immobilisation).3 The duration of overall therapy should be individualised after careful assessment of the treatment benefit against the risk for bleeding.1,3
When prevention of recurrent DVT / PE is indicated, the 2.5 mg twice-daily dose should be initiated following completion of 6 months of treatment with apixaban 5 mg twice daily or with another anticoagulant.3
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 VTE after initial treatment for acute DVT / PE with another anticoagulant.3 This is a decision for the prescribing clinician together with patient involvement in the decision-making.
NICE Guideline recommendations for starting anticoagulation for DVT or PE1
- Measure baseline full blood count, renal and hepatic function, PT and APTT but start anticoagulation before results available. Review and if necessary, act on results within 24 hours
- Offer anticoagulation for at least 3 months as a shared decision with the patient. This should take into account contraindications, comorbidities, adherence and the person’s preferences
- After 3 months (3 to 6 months for active cancer†) assess and discuss the benefits and risks of continuing, stopping or changing the anticoagulant with the person
† 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.3
Agree a plan for monitoring and follow-up with people having outpatient anticoagulant treatment for suspected or confirmed low-risk PE. Give them1:
- written information on symptoms and signs to look out for, including the potential complications of thrombosis and of treatment
- direct contact details of a healthcare professional or team with expertise in thrombosis who can discuss any new symptoms or signs, or other concerns
- information about out-of-hours services they can contact when their healthcare team is not available
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).
In Treatment of VTE: Treatment of VTE | Anticoagulation for the management of VTE | Initial management of a confirmed VTE | DOACs for the treatment of VTE and prevention of recurrent VTE |
Abbreviations
ARR=Absolute Risk Reduction BD=Twice Daily CRNM=Clinically Relevant Non-Major DOAC=Direct-acting Oral Anticoagulant DVT=Deep Vein Thrombosis INR=International Normalised Ratio ITT=Intention-To-Treat LMWH=Low Molecular Weight Heparin MHRA=Medicines and Healthcare products and Regulatory Agency NICE=National Institute for Health and Care Excellence PE=Pulmonary Embolism RR=Relative Risk RRR=Relative Risk Reduction SMC=Scottish Medicines Consortium smPC=Summary of Product Characteristics VKA=Vitamin K Antagonist VTE=Venous Thromboembolism
References
- NICE. Venous thromboembolic diseases: diagnosis, management and thrombophilia testing [NG158]. 26 March 2020.
- Agnelli G et al. N Engl J Med 2013; 369: 799–808.
- Apixaban Summary of Product Characteristics. Available at: www.medicines.org.uk/emc/search?q=apixaban.
- Dabigatran Summary of Product Characteristics. Available at: www.medicines.org.uk/emc/search?q=dabigatran.
- Edoxaban Summary of Product Characteristics. Available at: www.medicines.org.uk/emc/search?q=edoxaban.
- Rivaroxaban Summary of Product Characteristics. Available at: www.medicines.org.uk/emc/search?q=rivaroxaban.
- NICE Key Therapeutic Topic [KTT16]. Anticoagulants, including direct-acting oral anticoagulants (DOACs).
- NICE. Apixaban for the treatment and secondary prevention of deep vein thrombosis and/or pulmonary embolism [TA341].
- NICE. Rivaroxaban for the treatment of deep vein thrombosis and prevention of recurrent deep vein thrombosis and pulmonary embolism [TA261].
- NICE. Rivaroxaban for treating pulmonary embolism and preventing recurrent venous thromboembolism [TA287].
- NICE. Dabigatran etexilate for the treatment and secondary prevention of deep vein thrombosis and/or pulmonary embolism [TA327].
- NICE. Edoxaban for treating and for preventing deep vein thrombosis and pulmonary embolism [TA354].
- SIGN Advice: apixaban (Eliquis®).
- SIGN Advice: rivaroxaban (Xarelto®).
- SIGN Advice: dabigatran (Pradaxa®).
- SIGN Advice: edoxaban (Lixiana®).
- NICE. Quality Standard [QS15]. Patient Experience in adult NHS services.
Job code: 432-GB-2100110
Date of preparation: September 2021