The following are eight key points to remember from part 1 of this review on the selection of oral anticoagulants (OACs) for stroke prevention in nonvalvular atrial fibrillation (NVAF):

1. NVAF patients are at high risk of stroke and mortality.  This risk is significantly reduced with the use of OAC medications.
2. Up to 30% of NVAF patients from the four pivotal randomized trials of nonvitamin K antagonist OACs (NOACs; also known as direct oral anticoagulants) have concurrent coronary artery disease (CAD). Combined use of OAC and antiplatelet medications significantly increased the risk of major bleeding.
   1. Monotherapy with a NOAC is preferable for patients with NVAF and stable CAD (applicable to all NOACs). In selected patients, the addition of aspirin is still indicated in the long-term, based on individual risk assessment and coronary anatomy.
   2. In patients undergoing percutaneous coronary intervention who require “triple therapy” with OAC, aspirin and a second antiplatelet, well-controlled vitamin K antagonist (target therapeutic range [TTR] >70%, international normalized ratio [INR] range 2.0-2.5) or a NOAC may be chosen.
   3. Similar drug choice selection is applicable for patients with peripheral artery disease and concurrent NVAF as for patients with stable CAD and NVAF.
3. Cardioversion is associated with a 5-7% risk of clinical thromboembolic events within 1 month in NVAF patients without sufficient OAC. Silent brain lesions are common after NVAF ablation procedures (10-15% of patients), but their clinical relevance and implications are uncertain.
   1. Vitamin K antagonists remain the standard of care for NVAF patients undergoing cardioversion. NOACs are safe and effective with particular advantages (e.g., shortening the time to cardioversion), but ongoing trials will provide additional information about safety and efficacy.
   2. Warfarin remains the standard OAC of choice for patients undergoing NVAF ablation procedures. Uninterrupted dabigatran, apixaban, or rivaroxaban are reasonable alternatives, as is interrupted warfarin with bridging heparin therapy.
4. Patients with mechanical valve prostheses or moderate-severe rheumatic mitral stenosis are not good candidates for NOAC therapy and should be treated with vitamin K antagonists.
   1. Patients with other valvular abnormalities (e.g., mitral, aortic, and tricuspid insufficiency and aortic stenosis) may be safely treated with a NOAC (especially apixaban or rivaroxaban) or vitamin K antagonist.
5. Patients with high-quality vitamin K antagonist therapy (TTR >70%) have a low risk of thromboembolism and bleeding.
   1. It is reasonable to continue warfarin therapy for patients who have a TTR >70%. Changing from warfarin to a NOAC may be considered for patients with prior complications, higher SAMe-TT₂R₂ score, or based on individual patient preferences.
6. Patients with NVAF and a single stroke risk factor (other than gender) are at modestly elevated risk for stroke.
   1. In patients with a single stroke risk factor other than gender, OAC should be considered based on limited clinical trial data of dabigatran or apixaban.
7. NVAF, even when paroxysmal, is usually progressive. Hence, patients with a first-documented episode of NVAF should be considered at sufficient risk of stroke to warrant OAC consideration.
   1. The pattern of NVAF, frequency of NVAF episodes, or number of NVAF episodes should not influence OAC selection.
8. Commonly used antiarrhythmic medications frequently have interactions with vitamin K antagonist activity and metabolism, but rarely interact with NOAC.
   1. The dose of dabigatran or edoxaban (but not rivaroxaban or apixaban) should be reduced in patients taking verapamil.
   2. Dabigatran is contraindicated in combination with dronedarone. Edoxaban should be used at the 30 mg dose in patients taking dronedarone.

[Editor’s Note: Per the FDA prescribing documents, when dabigatran is used concurrently with dronedarone, the dose should be reduced to 75 mg (where available) for patients with a creatinine clearance (CrCl) of 30-50 ml/min. Dabigatran should not be used concurrently with dronedarone in patients with a CrCl ≤30 ml/min.]

Keywords: Anticoagulants, Arrhythmias, Cardiac, Aortic Valve Stenosis, Aspirin, Atrial Fibrillation, Coronary Artery Disease, Electric Countershock, Heparin, Mitral Valve Stenosis, Peripheral Arterial Disease, Primary Prevention, Prostheses and Implants, Risk Factors, Stroke, Thromboembolism, Vascular Diseases, Verapamil, Vitamin K, Warfarin

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