Indications for NOAC usage still limited

Aimee Lettis from the GP Update team gives us short, sharp nuggets of clinical information for sessional GPs.

You are probably aware of the NOACs (novel oral anticoagulants), new drugs that can be used in place of warfarin. You probably won’t be using them very often but here’s an overview to help you when faced with a patient asking to start one of them  or prescribing for the first time. There are three of them: dabigatran, rivaroxaban and apixaban and currently they have the following license/approval:

  • Stroke prevention in non-valvular atrial fibrillation (AF)
    • All 3 are licensed for this indication.
    • Apixaban is awaiting NICE/SIGN approval.
  • Prevention of venous thromboembolism (VTE) after elective knee/hip replacement
    • All 3 are licensed and approved by NICE.
  • Treatment of VTE
    • Only rivaroxaban is licensed & approved (NICE).

We have summarised the key information about the NOACs and compared the 3 in this table:

Dabigatran (Pradaxa) Rivaroxaban (Xaralto) Apixaban (Eliquis)
Preparation 110mg & 150mg tablets 10mg, 15mg  & 20mg tablets 2.5mg tablets
Dose in AF 110mg or 150mg twice daily. 20mg once daily reducing to 15mg once daily if eGFR 30-60. 5mg twice daily Reduce to 2.5mg twice daily if ≥ 2 of following:≥ 80y, ≤ 60kg or Cr ≥ 133.
Dose for VTE prevention post-surgery 220mg once daily  for:10d post knee surgery4-5w post hip surgery 10mg once daily for:2w post knee surgery5w post hip surgery 2.5mg twice daily for:10-14d post knee surgery32-38d post hip surgery
Dose for VTE treatment Not licensed 15mg twice daily for 21d then 20mg daily Not licensed
Reversal

No antidote available if rapid reversal required

(e.g. for emergency surgery, catastrophic bleeding).

In specialist centres, certain specialist blood products may be given.

Diet

No dietary restrictions are required.

Costs (for AF) £920/y which is mainly drug costs (DTB) £705/y (drug costs only) (NICE) Awaiting NICE approval and costings.
 

Warfarin costs around £426/y which includes all NHS costs such as drug, phlebotomy and lab time, but not patient costs (DTB).

Monitoring

No monitoring of coagulation needed.

Check eGFR before starting then annually if: ≥ 75y, weight < 50kg or eGFR 30-50.  
Renal/liver disease (from BNF) Renal:Avoid if eGFR <30.If eGFR 30-60, reduce to 150mg once daily.Liver:

Avoid in severe liver disease especially if coagulopathy.

Renal:Avoid if eGFR <15.Caution if eGFR 15-60.Liver:

May be used in moderate hepatic impairment as long as no coagulopathy.

Renal:Avoid if eGFR <15.Caution if eGFR 15-29.Liver:

Avoid in severe impairment and if coagulopathy associated with hepatic disease.

Common side effects (see BNF for details) Nausea, diarrhoea, dyspepsia, and abdominal pain Nausea and abnormal LFTs. Nausea.

Anaemia/bleeding are recognised side effects.

Interactions

Many! Check with BNF before prescribing and seek advice if needed!

Do not use with NSAIDs (because of increased bleeding risk).

(References: DTB 2011;49(10):114, NICE 2012, TA249 (dabigatran) and TA 256 (rivaroxaban), SPC for each drug accessed Jan 16th 2013).
The critical thing about NOACs is that they require no monitoring of their anticoagulant effect. However, remember that we have limited data on long-term safety and there is no antidote if rapid reversal is needed. Studies have shown some benefits over warfarin in terms of stroke prevention (NEJM 2011; 363:1875, NEJM 2011; 365:883, NEJM 2011; 365:981) but the benefits are not huge.
The DTB has reviewed the evidence (DTB 2011; 49(10):114) on dabigatran (yet to review the other two) and concluded that warfarin should remain first line therapy for anticoagulation in AF and dabigatran should be reserved for:
  • Those at high risk of stroke in whom INR monitoring is difficult
  • Those with poor anticoagulation control
  • Those at high risk of drug interactions.
No doubt local guidelines will proliferate which may give us a clearer indication for who to offer NOACs to. For now though, I’m sticking to the DTB guidance and would only use it in the limited situations above.
This article was published in the NASGP Newsletter April/May 2013.

Aimee Lettis

Aimee Lettis from the GP Update team gives us short, sharp nuggets of clinical information for sessional GPs. The GP Update team run one-day courses, bringing GPs up to date with all the latest evidence and guidelines.

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