The emergence of new oral anticoagulants (NOACs) presents pharmacists with an opportunity to intervene in assisting patients with selecting the most appropriate drug therapy. A recently published review on this topic highlighted several key points to consider when selecting the most appropriate agent based on patient-specific characteristics.
Here is the first part of a summary I put together regarding optimized stroke prevention in patients with NVAF.

• Up to 30% of NVAF patients from 4 pivotal randomized trials of NOACs have concurrent coronary artery disease (CAD).
  • Combined use of oral anticoagulation and antiplatelet medications significantly increased the risk of major bleeding. NOAC monotherapy is preferable for patients with NVAF and stable CAD. In select patient populations (eg, those with recent myocardial infarction or coronary artery stenting), the addition of aspirin is still indicated based on individual risk assessment of bleeding and the coronary anatomy. 
  • In patients undergoing percutaneous coronary intervention who require “triple therapy” with an oral anticoagulant, aspirin, and a second antiplatelet, a well-controlled vitamin K antagonist (VKA) [target therapeutic range (TTR) >70%, international normalized ratio (INR) range 2.0-2.5] or NOAC may be selected. If a NOAC is chosen, consideration can be given to a lower dose when combined with dual antiplatelet therapy (eg, rivaroxaban 15 mg daily). However, this strategy has not been formally studied.
• Cardioversion is associated with a 5% to 7% risk of clinical thromboembolic events within 1 month in NVAF patients without a sufficient oral anticoagulant. Silent brain lesions are common after NVAF ablation procedures (10% to 15% of patients), but their clinical relevance and implications are uncertain. VKAs remain the standard of care for NVAF patients undergoing cardioversion. NOACs are safe and effective with particular advantages (eg, shortening the time to cardioversion), but ongoing trials will provide additional evidence on safety and efficacy. Warfarin remains the standard oral anticoagulant of choice for patients undergoing NVAF ablation procedures. Uninterrupted dabigatran, apixaban, or rivaroxaban are reasonable alternatives.
• Patients with mechanical valve prostheses or moderate-severe rheumatic mitral stenosis are not good candidates for NOAC therapy and should instead be treated with VKAs. Patients with other valvular abnormalities (eg, mitral, aortic, and tricuspid insufficiency and aortic stenosis) may be safely treated with a NOAC (especially apixaban or rivaroxaban) or VKA.
• Patients with high-quality VKA therapy (TTR >70%) have a low risk of thromboembolism and bleeding. 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 or a higher SAMe-TT₂R₂ score (Table), or based on individual patient preferences. A total score of 0-2 points suggests that a patient may be able to achieve high-quality anticoagulation with warfarin-based therapy.
  • Table: Calculation of SAMe-TT₂R₂ Score
    • Sex (female): 1 Point
    • Age (>60 years): 1 Point
    • Medical history*: 1 Point, Medical history= 2 or more of the following conditions: hypertension, diabetes, coronary artery disease/myocardial infarction, peripheral arterial disease, congestive heart failure, previous stroke, pulmonary disease, hepatic or renal disease.
    • Treatment (rhythm control strategy): 1 Point
    • Tobacco use (within 2 years): 2 Points
    • Race (non-Caucasian): 2 Points
    • Maximum score: 8 Points

• Patients with NVAF and a single stroke risk factor (CHA₂DS₂-VASC score of 1 in males and 2 in females) are at modestly elevated risk for stroke. In patients with a single stroke risk factor other than gender, an oral anticoagulant should be considered based on limited clinical trial data of dabigatran or apixaban.
• Even when it is paroxysmal, NVAF is usually progressive. Therefore, patients with a first-documented episode of NVAF should be considered at sufficient risk of stroke to warrant consideration for an oral anticoagulant. The pattern of NVAF, frequency of NVAF episodes, or number of NVAF episodes should not influence oral anticoagulant selection.
• Commonly used antiarrhythmic medications frequently have interactions with VKA activity and metabolism, but rarely interact with NOACs. The dose of dabigatran or edoxaban (but not rivaroxaban or apixaban) should be reduced in patients taking verapamil. Dabigatran is contraindicated in combination with dronedarone. Edoxaban should be used at the 30 mg dose in patients taking dronedarone. Amiodarone use is generally safe to administer with all of the available NOAC agents.
• While warfarin is superior to aspirin and placebo for secondary stroke prevention in NVAF patients, meta-analysis has demonstrated the superiority of new OACs (NOACs, also known as direct oral anticoagulants) over warfarin. NOACs, as a group, are superior to warfarin for secondary stroke prevention in patients with NVAF. Aspirin should not be used for secondary stroke prevention in NVAF patients. The combination of OAC plus aspirin does not prevent major ischemic events better than OAC monotherapy, and it should be restricted to specific high-risk periods (ie, those with recent acute coronary syndrome or placement of coronary artery stenting).
• Anticoagulation is a relative contraindication to thrombolysis in the setting of acute ischemic stroke because of the increased risk of intracerebral hemorrhage. The use of laboratory tests can assess the degree of anticoagulation and risk of intracranial bleeding. 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). Mechanical thrombectomy can be considered for appropriate patients with effective systemic anticoagulation.
• 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. In NVAF patients following a TIA, OAC (including NOAC) may be initiated on the first day after neuroimaging has excluded intracranial hemorrhage. 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).
• Several NOACs increase the risk of major gastrointestinal bleeding when compared with warfarin in NVAF patients. 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. 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. As with warfarin, NOACs should be restarted as soon as safely possible following a gastrointestinal bleeding event. Gastrointestinal bleeding risk increased with concurrent antiplatelet use and age ≥75 years.
• 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. For patients with NVAF and stage III chronic kidney disease (creatinine clearance [CrCl] 30-49 ml/min), apixaban 2.5 mg to 5 mg twice daily, rivaroxaban 15 mg daily, or edoxaban 30 mg daily is preferred. Patients with CrCl values <30 ml/min were generally excluded from NOAC trials. As such, data regarding the safety of these agents in patients with more advanced kidney disease does not exist. For patients with NVAF on hemodialysis, vitamin K antagonist therapy should be considered first-line therapy, and the NOACs should be avoided. For patients with NVAF and a CrCl >95 ml/min, edoxaban 60 mg daily should not be used.
• Stroke and bleeding risk increase with age. However, the net clinical benefit usually favors use of OAC among older NVAF patients. For patients ages ≥75 years, apixaban 2.5 mg to 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.
• Adherence is a key factor to OAC efficacy for stroke prevention in NVAF patients. OAC should not be used in patients with intentional nonadherence. Understanding reasons for unintentional non-adherence and strategies to improve adherence (eg, use of pillboxes, family member engagement, and consideration of NOAC therapy) are important for effective stroke prevention in NVAF patients.