Appropriate use of drugs to prevent thromboembolism in patients with atrial fibrillation (AF ) involves comparing the patient's risk of stroke and risk of hemorrhage.

Preventing thromboembolism: recommendations


Class I

1) Antithrombotic therapy to prevent thromboembolism is recommended for all patients with atrial fibrillation, except those with lone atrial fibrillation or contraindications. ( Level of Evidence: A )

2) The selection of the antithrombotic agent should be based upon the absolute risks of stroke and bleeding and the relative risk and benefit for a given patient. ( Level of Evidence: A )

3) For patients without mechanical heart valves at high risk of stroke, chronic oral anticoagulant therapy with a vitamin K antagonist is recommended in a dose adjusted to achieve the target intensity international normalized ratio ( INR ) of 2.0 to 3.0, unless contraindicated. Factors associated with highest risk for stroke in patients with atrial fibrillation are prior thromboembolism ( stroke, transient ischemic attack [TIA], or systemic embolism ) and rheumatic mitral stenosis. ( Level of Evidence: A )

4) Anticoagulation with a vitamin K antagonist is recommended for patients with more than 1 moderate risk factor. Such factors include age 75 y or greater, hypertension, heart failure, impaired left ventricular systolic function ( ejection fraction 35% or less or fractional shortening less than 25% ), and diabetes mellitus. ( Level of Evidence: A )

5) INR should be determined at least weekly during initiation of therapy and monthly when anticoagulation is stable. ( Level of Evidence: A )

6) Aspirin, 81–325 mg daily, is recommended as an alternative to vitamin K antagonists in low-risk patients or in those with contraindications to oral anticoagulation. ( Level of Evidence: A )

7) For patients with atrial fibrillation who have mechanical heart valves, the target intensity of anticoagulation should be based on the type of prosthesis, maintaining an INR of at least 2.5. ( Level of Evidence: B )

8) Antithrombotic therapy is recommended for patients with atrial flutter as for those with atrial fibrillation. ( Level of Evidence: C )


Class IIa

1) For primary prevention of thromboembolism in patients with nonvalvular atrial fibrillation who have just 1 of the following validated risk factors, antithrombotic therapy with either Aspirin or a vitamin K antagonist is reasonable, based upon an assessment of the risk of bleeding complications, ability to safely sustain adjusted chronic anticoagulation, and patient preferences: age greater than or equal to 75 y ( especially in female patients ), hypertension, heart failure, impaired LV function, or diabetes mellitus. ( Level of Evidence: A )

2) For patients with nonvalvular atrial fibrillation who have 1 or more of the following less well-validated risk factors, antithrombotic therapy with either Aspirin or a vitamin K antagonist is reasonable for prevention of thromboembolism: age 65 to 74 y, female gender, or CAD. The choice of agent should be based upon the risk of bleeding complications, ability to safely sustain adjusted chronic anticoagulation, and patient preferences. ( Level of Evidence: B )

3) It is reasonable to select antithrombotic therapy using the same criteria irrespective of the pattern (i.e., paroxysmal, persistent, or permanent) of atrial fibrillation. ( Level of Evidence: B )

4) In patients with atrial fibrillation who do not have mechanical prosthetic heart valves, it is reasonable to interrupt anticoagulation for up to 1 wk without substituting heparin for surgical or diagnostic procedures that carry a risk of bleeding. ( Level of Evidence: C )

5) It is reasonable to reevaluate the need for anticoagulation at regular intervals. ( Level of Evidence: C )


Class IIb

1) In patients 75 y of age and older at increased risk of bleeding but without frank contraindications to oral anticoagulant therapy, and in other patients with moderate risk factors for thromboembolism who are unable to safely tolerate anticoagulation at the standard intensity of INR 2.0 to 3.0, a lower INR target of 2.0 ( range 1.6 to 2.5 ) may be considered for primary prevention of ischemic stroke and systemic embolism. ( Level of Evidence: C )

2) When surgical procedures require interruption of oral anticoagulant therapy for longer than 1 wk in high-risk patients, unfractionated heparin may be administered or low-molecular-weight heparin given by subcutaneous injection, although the efficacy of these alternatives in this situation is uncertain. ( Level of Evidence: C )

3) Following percutaneous coronary intervention or revascularization surgery in patients with atrial fibrillation, low-dose Aspirin ( less than 100 mg per d ) and/or Clopidogrel ( Plavix; 75 mg per d ) may be given concurrently with anticoagulation to prevent myocardial ischemic events, but these strategies have not been thoroughly evaluated and are associated with an increased risk of bleeding. ( Level of Evidence: C )

4) In patients undergoing percutaneous coronary intervention, anticoagulation may be interrupted to prevent bleeding at the site of peripheral arterial puncture, but the vitamin K antagonist should be resumed as soon as possible after the procedure and the dose adjusted to achieve an INR in the therapeutic range. Aspirin may be given temporarily during the hiatus, but the maintenance regimen should then consist of the combination of Clopidogrel, 75 mg daily, plus Warfarin ( INR 2.0 to 3.0 ). Clopidogrel should be given for a minimum of 1 mo after implantation of a bare metal stent, at least 3 mo for a Sirolimus-eluting stent, at least 6 mo for a Paclitaxel-eluting stent, and 12 mo or longer in selected patients, following which Warfarin may be continued as monotherapy in the absence of a subsequent coronary event. When Warfarin is given in combination with Clopidogrel or low-dose Aspirin, the dose intensity must be carefully regulated. ( Level of Evidence: C )

5) In patients with atrial fibrillation younger than 60 y without heart disease or risk factors for thromboembolism ( lone atrial fibrillation ), the risk of thromboembolism is low without treatment and the effectiveness of aspirin for primary prevention of stroke relative to the risk of bleeding has not been established. ( Level of Evidence: C )

6) In patients with atrial fibrillation who sustain ischemic stroke or systemic embolism during treatment with low-intensity anticoagulation ( INR 2.0 to 3.0 ), rather than add an antiplatelet agent, it may be reasonable to raise the intensity of the anticoagulation to a maximum target INR of 3.0 to 3.5. ( Level of Evidence: C )



Class III

1) Long-term anticoagulation with a vitamin K antagonist is not recommended for primary prevention of stroke in patients below the age of 60 y without heart disease ( lone atrial fibrillation ) or any risk factors for thromboembolism. ( Level of Evidence: C )

Source: Circulation, 2006


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