From the Guidelines
Aspirin is the most appropriate initial oral antithrombotic therapy for AD, who has been diagnosed with embolic stroke of undetermined source (ESUS). For patients with ESUS, current evidence supports starting with a single antiplatelet agent, with aspirin being the first-line choice, as indicated in the 2023 systematic review and synthesis of global stroke guidelines 1. The typical dosage is 81-325 mg daily. While direct oral anticoagulants like apixaban have been studied in ESUS, clinical trials have not shown them to be superior to aspirin for preventing recurrent stroke in this specific condition, and they carry a higher bleeding risk. Dual antiplatelet therapy with aspirin plus clopidogrel is not recommended for long-term secondary prevention in ESUS as it increases bleeding risk without providing additional benefit over aspirin alone, as supported by guidelines from the American Heart Association/American Stroke Association 1. Similarly, the combination of aspirin plus dipyridamole, while used in some stroke patients, is not the first-line choice for ESUS. Key considerations in the management of ESUS include:
- The use of antiplatelet agents rather than oral anticoagulation to reduce the risk of recurrent stroke and other cardiovascular events 1
- Individualization of the antiplatelet agent based on patient risk factor profiles, cost, tolerance, and other clinical characteristics 1
- The potential need to reassess the treatment approach if additional diagnostic information becomes available that identifies a specific stroke etiology, such as paroxysmal atrial fibrillation, which would warrant anticoagulation instead. In summary, the most appropriate initial oral antithrombotic therapy for AD is aspirin, given its established efficacy and safety profile in the context of ESUS, as supported by the most recent and highest quality evidence 1.
From the FDA Drug Label
The FDA drug label does not answer the question.
From the Research
Initial Oral Antithrombotic Therapy for Embolic Stroke of Undetermined Source (ESUS)
The most appropriate initial oral antithrombotic therapy for AD, a 68-year-old male diagnosed with ESUS, can be determined based on the provided evidence.
- Aspirin plus clopidogrel: This combination has been recommended for patients with symptomatic intracranial atherosclerosis (ICAS) 2. However, its effectiveness in ESUS is not directly addressed in the provided studies.
- Aspirin: Aspirin is a commonly used antithrombotic agent for secondary prevention of stroke. The study by 3 shows that aspirin plus dipyridamole is beneficial in reducing the recurrence of stroke, but it does not directly compare aspirin monotherapy to other options in ESUS patients.
- Apixaban: A recent study 4 compared apixaban to aspirin in patients with ESUS and found that apixaban was not superior to aspirin in preventing new ischemic lesions.
- Aspirin plus dipyridamole: This combination has been shown to be effective in reducing the recurrence of stroke 3, 5. However, its effectiveness in ESUS patients is not directly addressed in the provided studies.
Comparison of Antithrombotic Therapies
Based on the available evidence, the most appropriate initial oral antithrombotic therapy for AD cannot be determined with certainty. However, aspirin is a commonly used and well-established option for secondary prevention of stroke. The combination of aspirin plus dipyridamole may also be considered, as it has been shown to be effective in reducing the recurrence of stroke in certain patient populations 3, 5. Apixaban, on the other hand, was not found to be superior to aspirin in ESUS patients 4. Aspirin plus clopidogrel may be considered in patients with ICAS, but its effectiveness in ESUS is not directly addressed in the provided studies 2.