The following are seven key points to remember from part 2 of this review on the selection of oral anticoagulants (OAC) for stroke prevention in nonvalvular atrial fibrillation (NVAF):

1. While warfarin is superior to aspirin and placebo for secondary stroke prevention in NVAF patients, meta-analysis has demonstrated superiority of nonvitamin K antagonist OACs (NOACs; also known as direct oral anticoagulants) over warfarin.
   1. NOACs, as a group, are superior to warfarin for secondary stroke prevention in patients with NVAF.
   2. Aspirin should not be used for secondary stroke prevention in NVAF patients.
   3. The combination of OAC plus aspirin does not prevent major ischemic events better than OAC monotherapy, and should be restricted to specific high-risk periods.
2. Anticoagulation is a contraindication to thrombolysis in the setting of acute ischemic stroke because of increased risk of intracerebral hemorrhage. Use of laboratory tests can assess the degree of anticoagulation and risk of intracranial bleeding.
   1. After careful risk/benefit discussion, intravenous thrombolysis may be given if coagulation tests for a specific NOAC or vitamin K antagonist reveal low or absent anticoagulant intensity (off-label).
   2. Mechanical thrombectomy can be considered for appropriate patients with effective systemic anticoagulation.
3. Following an ischemic stroke or transient ischemic attack (TIA) associated with NVAF, patients are at elevated risk of both recurrent thromboembolism without anticoagulation and bleeding associated with anticoagulant initiation.
   1. In NVAF patients following a TIA, OAC (including NOAC) may be initiated on the first day after neuroimaging has excluded intracranial hemorrhage.
   2. In NVAF patients, OAC treatment may be initiated after 3 days (minor stroke), 5-7 days (moderate severity stroke), or 12-14 days (severe stroke).
4. Several NOACs increase the risk of major gastrointestinal bleeding when compared to warfarin in NVAF patients.
   1. Apixaban 5 mg twice daily or dabigatran 110 mg twice daily (where available) are first choice therapies for stroke prevention in NVAF patients with a high risk of gastrointestinal bleeding.
   2. Dabigatran 150 mg twice daily, edoxaban 60 mg daily, and rivaroxaban 20 mg daily are second-line choices for patients at high risk for gastrointestinal bleeding.
   3. As with warfarin, NOACs should be restarted as soon as safely possible following a gastrointestinal bleeding event.
   4. Gastrointestinal bleeding risk increased with concurrent antiplatelet use and age ≥75 years.
5. Chronic kidney disease is an important risk factor for both stroke and bleeding in anticoagulated patients with NVAF. Most of the NOACs are at least partially cleared via renal mechanisms and therefore require dose adjustment or avoidance.
   1. For patients with NVAF and stage III chronic kidney disease (creatinine clearance [CrCl] 30-49 ml/min), apixaban 2.5-5 mg twice daily, rivaroxaban 15 mg daily, or edoxaban 30 mg daily is preferred.
   2. For patients with NVAF on hemodialysis, no anticoagulation or vitamin K antagonist therapy is appropriate, and NOAC therapy should be avoided.
   3. For patients with NVAF and a CrCl >95 ml/min, edoxaban 60 mg daily should not be utilized.
6. Stroke and bleeding risk increase with age. However, the net clinical benefit usually favors use of OAC among older NVAF patients.
   1. For patients ages ≥75 years, apixaban 2.5-5 mg twice daily is the first-line choice. Dabigatran 110 mg twice daily (where available), rivaroxaban 20 mg daily, or edoxaban 60 mg daily are alternatives.
7. Adherence is a key factor to OAC efficacy for stroke prevention in NVAF patients.
   1. OAC should not be used in patients with intentional nonadherence.
   2. Understanding reasons for unintentional nonadherence and strategies to improve adherence (e.g., use of pill boxes, family member engagement, consideration of NOAC therapy) are important for effective stroke prevention in NVAF patients.

Keywords: Anticoagulants, Arrhythmias, Cardiac, Aspirin, Atrial Fibrillation, Cerebral Hemorrhage, Intracranial Hemorrhages, Ischemic Attack, Transient, Primary Prevention, Renal Insufficiency, Chronic, Risk Factors, Thrombectomy, Thromboembolism, Vitamin K, Warfarin, Vascular Diseases

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