DOACs for the treatment of VTE and prevention of recurrent VTE
Click here to view ELIQUIS® (apixaban) prescribing and adverse event reporting information.
Treatment of VTE and prevention of recurrent VTE depends on local policy. One approach is the administration of LMWH concurrently with a VKA for at least 5 days, followed by VKA on its own once the INR is at least 2.1 However, DOACs have emerged as valid options to treat VTE1 and are increasingly being used in clinical practice,2 due to their stable therapeutic effect, reduced interactions with other medications and food, and reduced need for regular monitoring.3
DOACs have been shown to reduce the treatment burden compared with VKAs, including by offering shorter time to discharge from hospital in acute VTE.4,5 Patients receiving DOACs to treat DVT / PE have also reported higher treatment satisfaction compared with those on VKA.6-9
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.
A further advantage of the DOACs apixaban and rivaroxaban is that they offer a useful oral single drug approach, allowing patients to start and continue on the same therapy for as long as required, based on their individual risks.10,11 Details of the dosing regimens for each DOAC are shown below.10-13
Please refer to the individual DOAC SmPCs for full dosing recommendations.
* Short duration of therapy (at least 3 months) should be based on transient risk factors (e.g. recent surgery, trauma, immobilisation). The duration of overall therapy should be individualised after careful assessment of the treatment against the risk for bleeding.10-13
† 150 mg or 110 mg should be selected based on an individual assessment of the thromboembolic risk and risk of bleeding.12
[References for image: 10. Apixaban Summary of Product Characteristics. 11. Rivaroxaban Summary of Product Characteristics. 12. Dabigatran Summary of Product Characteristics. 13. Edoxaban Summary of Product Characteristics.]
Alongside the decision to use a single-drug approach with rivaroxaban or apixaban, or a DOAC that requires initial treatment with LMWH like dabigatran or edoxaban, there are other considerations when selecting a DOAC for your patient with VTE, such as contraindications or the dosing regimen. As patients should be actively involved in the decision-making process, it is important to provide information on all relevant treatment options, including the benefits, risks and potential consequences, and to consider patient preference.15
Contraindications10-14
For full contraindications please refer to individual product prescribing information.
Efficacy and safety of DOACs in acute treatment
The efficacy and safety of DOACs for the treatment of VTE and prevention of recurrent VTE have been assessed in randomised controlled trials. The results of key clinical trials investigating the DOACs shown below provide an overview of the efficacy and safety profiles of DOACs vs. LMWH/warfarin in the treatment of VTE.16-19
It should be noted that there are no head-to-head randomised clinical trials comparing the DOACs, and comparisons cannot be made between individual DOACs based on these data. Please refer to the individual SmPCs for further information.10-14
Study designs of key clinical trials assessing the DOACs8,11,16-21
* Duration of treatment was determined by the treating physician before randomisation. Most patients received 6 or 12 months of therapy, or both.11
† Patients with body weight ≤60 kg or CrCl 30–50 ml/min, or patients receiving concomitant potent P-gp inhibitors received edoxaban 30 mg OD.16,21
Efficacy of DOACs vs warfarin for recurrent VTE/VTE-related death prevention in patients with VTE:
Efficacy of apixaban vs. enoxaparin / warfarin: The AMPLIFY clinical trial10,17
*The primary efficacy endpoint was the incidence of the adjudicated composite of recurrent symptomatic VTE or death related to VTE.17 Recurrent VTE included fatal or non-fatal PE and DVT.17
References: 10. ELIQUIS (apixaban) summary of Product Characteristics. 17. Agnelli G et al. N Engl J Med 2013; 369: 799-808.
Efficacy of rivaroxaban vs. enoxaparin / warfarin: EINSTEIN pooled Analysis11,20
*The primary efficacy endpoint was symptomatic recurrent VTE defined as the composite of recurrent DVT or fatal or non-fatal PE.11
References: 11. Rivaroxaban Summary of Product Characteristics. 20. Prins MH et al. Thrombosis Journal 2013; 11: 21.
Efficacy of dabigatran vs. heparin / warfarin: RE-COVER pooled analysis12,19
RE-COVER and RE-COVER II were separate trials; the data presented here are pooled results from the combination of RE-COVER and RE-COVER II.12 Both trials had a randomised, double-blind, double-dummy design to compare dabigatran 150 mg twice daily with warfarin, adjusted to maintain an INR of 2.0 to 3.0 during 6 months, after initial parenteral anticoagulation (LMWH, UFH or fondaparinux).19
*The primary efficacy endpoint was the composite of recurrent symptomatic DVT and / or PE and related deaths within the 6-month treatment period plus an additional 30-day follow-up.19
References: 12. Pradaxa (dabigatran) Summary of Product Characteristics. 19. Schulman S et al. Circulation 2014: 129: 764–772.
Efficacy of edoxaban vs. enoxaparin / warfarin: The HOKUSAI-VTE trial13,16
*The primary efficacy endpoint was adjudicated symptomatic recurrent VTE defined as the composite endpoint of DVT, non-fatal PE and fatal PE.16
References: 13. Lixiana (edoxaban) Summary of Product Characteristics. 16. The Hokusai-VTE investigators. N Engl J Med 2013; 369: 1406–1415.
There are no head-to-head randomised clinical trials comparing the DOACs. Comparisons cannot be made between individual DOACs based on these data.
Bleeding profiles for DOACs versus warfarin in patients with VTE
Bleeding profile of apixaban vs. enoxaparin / warfarin: AMPLIFY trial10,17
*The primary safety endpoint was the incidence of an adjudicate of major bleeding.17
† The secondary safety endpoint was a composite of major and CRNM bleeding.17
References: 10. ELIQUIS (apixaban) summary of Product Characteristics. 17. Agnelli G et al. N Engl J Med 2013; 369: 799-808.
Bleeding profile of rivaroxaban vs. enoxaparin / warfarin: EINSTEIN pooled analysis11,20
*The secondary safety endpoint was the incidence of major bleeding events.11
† The primary safety endpoint was the incidence of major or CRNM bleeding events.11
References: 11. Rivaroxaban Summary of Product Characteristics. 20. Prins MH et al. Thrombosis Journal 2013; 11: 21.
Bleeding profile of dabigatran vs. heparin / warfarin: RE-COVER pooled analysis12,19
*Safety endpoints included major and major / CRNM bleeding.12,19
RE-COVER and RE-COVER II were separate trials; the data presented here are pooled results from the combination of RE-COVER and RE-COVER II.12 Both trials had a randomised, double-blind, double-dummy design to compare dabigatran 150 mg twice daily with warfarin, adjusted to maintain an international normalised ratio (INR) of 2.0 to 3.0 during 6 months, after initial parenteral anticoagulation (LMWH, UFH or fondaparinux).19
References: 12. Pradaxa (dabigatran) Summary of Product Characteristics. 19. Schulman S et al. Circulation 2014: 129: 764–772.
Bleeding profile of edoxaban vs. enoxaparin / warfarin: The HOKUSAI-VTE trial13,16
*The safety endpoint shown is assumed from the study design; it was not specifically stated.16
† The primary safety endpoint was a composite of major / CRNM bleeding.16
References: 13. Lixiana (edoxaban) Summary of Product Characteristics. 16. The Hokusai-VTE investigators. N Engl J Med 2013; 369: 1406–1415.
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
BD=Twice Daily CrCl=Creatinine Clearance DOAC=Direct-acting Oral Anticoagulant DVT=Deep Vein Thrombosis HCP=Health Care Professional INR=International Normalised Ratio LMWH=Low Molecular Weight Heparin MHRA=Medicines and Healthcare products and Regulatory Agency OD=Once Daily PE=Pulmonary Embolism P-gp=P-glycoprotein smPC=Summary of Product Characteristics UFH=Unfractionated Heparin VKA=Vitamin K Antagonist VTE=Venous Thromboembolism
References
- Mazzolai L et al. Eur Heart J 2018; 39: 4208–4218.
- Kirchhof P et al. Eur Heart J 2016; 37: 2893–2962.
- Van Es J et al. J Thromb Haemost. 2011; 9 Suppl 1: 265–274.
- Basto AN et al. J Thromb Thrombolysis 2018; 45: 51–55.
- Nakamura M et al. Ann Vasc Dis 2017; 10: 92–98.
- Brekelmans MPA et al. Neth J Med 2017; 75: 50–55.
- Willich SN et al. Value Health 2014; 17: A496.
- Prins MH et al. Thromb Res 2015; 135: 281–288.
- Keita I et al. Patient Prefer Adher 2017; 11: 1625–1634.
- Apixaban Summary of Product Characteristics. Available at: www.medicines.org.uk/emc/search?q=apixaban.
- Rivaroxaban Summary of Product Characteristics. Available at: www.medicines.org.uk/emc/search?q=rivaroxaban.
- 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.
- Warfarin Summary of Product Characteristics. Available at: www.medicines.org.uk/emc/search?q=warfarin.
- NICE Quality Standard [QS15]. Patient experience in adult NHS services.
- The Hokusai-VTE Investigators. N Engl J Med 2013; 369: 1406–1415.
- Agnelli G et al. N Engl J Med 2013; 369: 799–808.
- Schulman S et al. N Engl J Med 2009; 361: 2342–2352.
- Schulman S et al. Circulation 2014; 129: 764–772.
- Prins MH et al. Thrombosis Journal 2013; 11: 21.
- Raskob G et al. J Thromb Haemost 2013; 11: 1287–1294.
Job code: 432-GB-2100110
Date of preparation: September 2021