Guidance on the prevention of stroke and systemic embolism in patients with atrial fibrillation continued

New oral anticoagulant therapies

• Two broad classes of new oral anticoagulant therapy are currently available or in development:
  direct thrombin inhibitor:
  • at the time of publication dabigatran is the only new oral anticoagulant with a licence for this indication
  • dabigatran is an alternative to warfarin in patients fulfilling the following criteria:
    • previous stroke, transient ischaemic attack (TIA), systemic embolism
    • left ventricular ejection fraction < 40%
    • symptomatic heart failure ≥ New York Heart Association (NYHA) class 2
    • aged ≥ 75 years
    • aged ≥ 65 years with one of the following: diabetes mellitus, coronary artery disease, hypertension
  • for most patients 150 mg bd should be used—the results of the RELY study showed statistically significant reduction in strokes and systemic emboli and a comparable bleeding risk to warfarin
  • in patients over the age of 80 years, and in patients receiving verapamil, the lower dose of 110 mg bd should be used:
    • this dose should also be considered for patients with gastritis and reflux disease, as well as in patients with other significant bleeding risk factors and low body weight
  • patients can be switched from warfarin to dabigatran once the INR has fallen below 2
  • it is advisable to take the medication with food in the morning and evening as dyspepsia is the most common side-effect experienced
  • capsules must not be opened and should be swallowed whole
  • for further information refer to the SPC and Prescriber guide
  • treatment with dabigatran in patients with severe renal impairment (creatinine clearance <30 ml/min) is contraindicated
• factor Xa inhibitors:
  • these drugs are currently in development
• Benefits of new oral anticoagulant agents include:
  • fixed dose
  • no routine coagulation monitoring
  • fewer drug and diet interactions
    
  • fast onset of action

• There are a number of other points to consider:
• as with all new drugs, there is a lack of long-term safety data
• these new therapies have a shorter half life compared with warfarin, which means that compliance is crucial. Shorter half lives result in faster loss of action and antithrombotic protection after omitting tablets or discontinuation. Therefore, missing tablets due to non-compliance will quickly lead to loss of stroke protection, which needs to be emphasised to patients
• although no antidote is currently available, advice is available on the management of overdose and experimental evidence exists on the role of some plasma components in the management of bleeding

• Patient education is necessary, especially with regard to compliance
• These new drugs are powerful anticoagulants and all the precautions of anticoagulants are still applicable

Antiplatelet therapy

• Aspirin alone:
• aspirin as monotherapy has a limited role for stroke prevention in AF but was previously used as it was the only alternative to warfarin
• aspirin is not recommended at any level of stroke risk due to increasing evidence that it is neither as effective nor as safe as thromboprophylaxis:
  • in the elderly, warfarin is superior to aspirin for stroke prevention, with similar rates of major bleeding and intracranial haemorrhage between warfarin and aspirin
• compared with aspirin, the new oral anticoagulants may have:
  • superior efficacy
  • similar bleeding risk

• Aspirin/clopidogrel combination therapy
  • the combination of aspirin/clopidogrel has reduced efficacy compared with warfarin with a similar risk of major and intracranial haemorrhages
  • aspirin/clopidogrel was superior to aspirin monotherapy in one study and so remains an option in patients at high risk according to CHA₂DS₂-VASc score but who cannot tolerate or do not wish to take any oral anticoagulant, and who are not at high risk of bleeding

Guidance on the prevention of stroke and systemic embolism in patients with atrial fibrillation continued

Assessing the risk of bleeding

• It is important to assess bleeding risk when initiating antithrombotic treatment with any oral anticoagulant or aspirin in order to guide appropriate dosing and monitoring

• Relevant risk factors for bleeding include:
  
  • non-correctable, such as age, previous stroke, chronic kidney disease
    
  • correctable, including:
    • uncontrolled hypertension
    • concomitant use of aspirin/NSAIDs
    • poor control of INR (labile INR)
    • alcohol intake

• The HAS-BLED score provides a simple and easy way to assess bleeding risk to help guide decisions on prescribing thromboprophylaxis in everyday clinical practice:
  
  • in patients at high risk of bleeding (HAS-BLED score ≥3):
    • the use of anticoagulation is not precluded
    • extra review and caution is needed following initiation of antithrombotic therapy, whether with oral anticoagulation or antiplatelet therapy
    • management of correctable risk factors for bleeding (e.g. hypertension, cessation of concomitant aspirin in anticoagulated patients, attention to improved INR, etc) should be considered

Prevention of stroke and systemic embolism in patients with atrial fibrillation

Guidance on the prevention of stroke and systemic embolism in patients with atrial fibrillation continued

Initiating treatment

• Thromboprophylaxis is recommended:
  • in the presence of one or more stroke risk factors based on the CHA₂DS₂-VASC score
  • following an assessment of bleeding risk

• Event rates quoted below are forevent rate per 100 person years

CHA₂DS₂-VASC score

• The risk of hospitalisation and death due to thromboembolism at 1 year is between 3.71–23.64

• The risk of stroke and the benefits of thromboprophylaxis are well established

• Oral anticoagulation is recommended:
  • the choice between warfarin and new oral anticoagulation therapies depends on local prescribing practices and individual patient assessment

CHA₂DS₂-VASC score = 1

• The risk of hospitalisation and death due to thromboembolism at 1 year is 2.01

• The risk of stroke in this group is relatively small and, therefore, the absolute net benefit of thromboprophylaxis is reduced
  

• Oral anticoagulation is recommended:
  • patient values/preferences should be considered, as should the balance between stroke prevention versus the need for monitoring (warfarin) and the risk of bleeding (any antithrombotic drug
  • echocardiographic risk factors may be useful to guide treatment decisions in patients with reversible contraindications in whom there is doubt about the presence of risk factors
    
  • anticoagulation with new oral anticoagulants may be preferred at annual stroke rates above 0.9%, which is nearly the same as CHA₂DS₂-VASc score of ≥1

CHA₂DS₂-VASC score = 1

• The risk of hospitalisation and death due to thromboembolism at 1 year is 0.78

• The risk of stroke is so small that no antithrombotic treatment is the preferred strategy

• Aspirin is sometimes prescribed but the risk of bleeding with aspirin is not negligible and needs to be considered

After cardioversion or ablation

• Oral anticoagulation therapy is recommended post-cardioversion or ablation in the presence of stroke risk factors or risk factors for AF recurrence, including long duration of prior AF, structural abnormalities on echocardiogram, previous failed cardioversions, etc

Educating patients

• All patients should be educated to:
  • increase understanding of their condition
  • help them understand that successful thromboprophylactic treatment is critically dependent on them taking their drugs with the correct timing and frequency
  • increase their awareness of drug interactions with new medications
  • encourage compliance with other medications to reduce their cardiovascular risk and self-manage their comorbidities

When to refer

• Patients should be referred to secondary care if they:
  • are unsuitable for, or unwilling to take, the treatment options mentioned above
  • have recent-onset AF and symptoms, as specialist advice is needed to guide the rhythm and rate control strategy; such referral should not delay the decision to treat with thromboprophylaxis