Anticoagulants used to prevent blood clots and strokes include;

  • Warfarin: inhibits the synthesis of vitamin K dependent coagulation factors
  • Dabigatran (Pradaxa®): a direct reversible thrombin (factor IIa) inhibitor
  • Apixaban (Eliquis®): reversibly inhibits factor Xa
  • Rivaroxaban (Xarelto®): direct reversible inhibitor of factor Xa

The Therapeutic Guidelines currently recommend warfarin as first-line treatment in people with non-valvular atrial fibrillation (AF) with moderate to high risk of stroke. However, these guidelines are due for review and the prescribing of new oral anticoagulants is increasing in the clinical setting. Key clinical trials comparing their activity to warfarin demonstrate that these agents are not inferior to warfarin with respect to stroke prevention and significant bleeding events

The perceived high risk of bleed, need for regular monitoring, and interactions with other medications and foods are some of the reasons why warfarin is underused. The newer anticoagulants: dabigatran, apixaban and rivaroxaban; address some of these concerns. However, as there is no readily available, validated method of measuring or reversing the activity of these new agents, a bleeding risk assessment of these patients is very important. The lack of antidote and clinical experience in managing major bleeds is a concern. Patients who are well-controlled on warfarin may therefore not benefit clinically from switching to a different anticoagulant.

Renal function needs to be assessed before starting any anticoagulant treatment, and at least annually thereafter. The dose may need to be adjusted depending on indication for therapy, level of renal impairment, age and/or weight.

Table 1: Dabigatran

Stroke prevention in non-valvular AF Prevention of VTE after hip/knee replacement
Normal adult dose 150mg twice daily 220mg once daily
Age > 75 years 110mg twice daily 220mg once daily
CrCl 30–50 mL/min or increased risk of bleeding Reduced dose of 110mg twice daily may be considered 150mg once daily
CrCl ≤ 29 mL/min Contraindicated Contraindicated

 

Table 2: Apixaban**

Stroke prevention in non-valvular AF Prevention of VTE after hip/knee replacement
Normal adult dose 5mg twice daily 2.5mg twice daily
Age > 80 years 2.5mg twice daily 2.5mg twice daily
CrCl 30–50 mL/min or increased risk of bleeding Reduced dose of 2.5mg twice daily may be considered 2.5mg twice daily
CrCl ≤ 25 mL/min Contraindicated* Contraindicated*

*Limited experience in patients with CrCl 15 to < 25 mL/min and no experience in patients with CrCl < 15 mL/min or on dialysis.

**Apixaban tablets can be taken with or without food.

 

Table 3: Rivaroxaban

Stroke prevention in non-valvular AF Prevention of VTE after hip/knee replacement DVT treatment and prevention of recurrent DVT and PE
Normal adult dose 20mg once daily 10mg once daily 15mg twice daily for three weeks, followed by 20mg once daily
CrCl 30–49 mL/min 15mg once daily 10mg once daily 15mg twice daily for three weeks, followed by 20mg once daily
CrCl 15–29 mL/min Contraindicated 10mg once daily (limited data is available therefore caution should be used in the interpretation of results) Contraindicated
CrCl < 15 mL/min or on dialysis Contraindicated Contraindicated Contraindicated

 

Rivaroxaban 10mg tablets can be taken with or without food, however rivaroxaban 15mg and 20mg tablets should be taken with food for optimal bioavailability.

Ensuring patients are compliant is important as these newer anticoagulants have a much shorter half-life than warfarin. Thus, if a dose is missed, the risk of stroke is increased.

Oral anticoagulants must be ceased in patients prior to undergoing surgical procedures with a high risk of bleeding. Current recommendations are that:

  • Warfarin be ceased three to five days prior to surgery and resumed as soon as possible thereafter
  • Dabigatran and rivaroxaban be ceased one to three days prior to surgery, and
  • Apixaban should be ceased at least three days prior to surgery due to potential for a greater incidence of bleeding.

Patients at high risk of thromboembolism usually require a substitute anticoagulant, for example heparin, enoxaparin or dalteparin, until haemostasis is achieved post-surgery. In the case of warfarin, crossover therapy is necessary until INR (international normalised ratio) is above two. The new anticoagulants have an immediate onset of action and therefore, crossover therapy is not necessary. These agents can be restarted after the operation when the next dose of the substitute would have been administered.

References:

  1. Brighton T. New oral anticoagulant drugs- mechanisms of action. Aust Presc. 2010; 33: 38-41.
  2. Mims Online [internet]. St Leonards, NSW: UBM Medica Australia Pty Ltd; 2015.
  3. National Prescribing Service. Anticoagulants: dose adjustment for newer anticoagulants. Strawberry Hills: Australian Government Department of Health; 2013.
  4. National Prescribing Service. Good anticoagulant practice. Strawberry Hills: Australian Government Department of Health; 2013.

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