How to work up and treat a patient with multiple recurrent ischemic strokes on dual antiplatelet therapy (DAPT) and Novel Oral Anticoagulants (NOACs)?

From the Guidelines

For a patient with multiple recurrent ischemic strokes despite being on dual antiplatelet therapy (DAPT) and Novel Oral Anticoagulants (NOACs), a comprehensive workup and treatment modification is essential, prioritizing the discontinuation of DAPT and continuation of NOACs, as the risk of bleeding outweighs the benefits of DAPT in this setting, as suggested by the 2021 guideline for the prevention of stroke in patients with stroke and transient ischemic attack 1.

Workup

The patient should be hospitalized for a thorough evaluation, including:

• Brain MRI to assess for any new or chronic ischemic changes
• Vascular imaging (carotid ultrasound, CT angiography) to evaluate for any significant stenosis or occlusions
• Cardiac assessment (echocardiogram, prolonged cardiac monitoring) to rule out any cardiac sources of embolism
• Extensive laboratory testing (lipid panel, hemoglobin A1c, hypercoagulability studies) to identify any underlying risk factors or conditions that may be contributing to the recurrent strokes

Treatment Modification

Consider the following modifications to the patient's treatment regimen:

• Discontinue DAPT, as the continuous use of DAPT for >90 days or the use of triple antiplatelet therapy is associated with excess risk of hemorrhage, as stated in the 2021 guideline 1
• Continue NOACs, as they are essential for stroke prevention in patients with atrial fibrillation, as recommended by the 2018 European Heart Rhythm Association practical guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation 1
• Add high-intensity statin therapy (atorvastatin 80mg or rosuvastatin 40mg daily) regardless of baseline lipid levels, as this has been shown to reduce the risk of recurrent ischemic stroke
• Aggressively manage all modifiable risk factors, including hypertension (target <130/80 mmHg), diabetes (target HbA1c <7%), smoking cessation, and weight management

Specialized Testing and Consultation

Consider specialized testing, such as platelet function assays, to identify potential antiplatelet resistance. For selected patients with intracranial atherosclerotic disease, angioplasty with stenting might be considered. Treatment failure despite optimal medical therapy may indicate an alternative stroke etiology, such as vasculitis, genetic disorders, or rare hypercoagulable states, requiring specialized testing and consultation with stroke specialists, hematologists, and vascular neurologists to develop a tailored approach for these challenging cases.

From the Research

Workup of Patient with Multiple Recurrent Ischemic Strokes on DAPT and NOACs

• The patient's medical history, including the type of stroke, should be thoroughly reviewed to determine the underlying cause of the recurrent strokes 2.
• Laboratory tests, such as complete blood count, blood chemistry, and coagulation studies, should be performed to identify any underlying conditions that may be contributing to the recurrent strokes.
• Imaging studies, such as MRI or CT scans, should be performed to evaluate the extent of the stroke and to identify any potential causes, such as vascular malformations or tumors.
• The patient's current medications, including DAPT and NOACs, should be reviewed to determine if they are effective and if any adjustments need to be made.

Treatment of Patient with Multiple Recurrent Ischemic Strokes on DAPT and NOACs

• The treatment of recurrent ischemic strokes should be individualized based on the patient's specific needs and medical history 3, 4.
• Antiplatelet therapy, such as aspirin or clopidogrel, may be recommended to reduce the risk of recurrent ischemic stroke 5, 6.
• Anticoagulant therapy, such as warfarin or NOACs, may be recommended for patients with cardioembolic stroke or other conditions that increase the risk of stroke 3, 4.
• Lifestyle modifications, such as tobacco cessation, decreased alcohol use, and increased physical activity, should be recommended to reduce the risk of recurrent stroke 5, 6.
• The patient's blood pressure, glucose, and lipid levels should be closely monitored and managed to reduce the risk of recurrent stroke 5, 6.

Management of Bleeding Risk

• The patient's bleeding risk should be carefully assessed and managed, particularly when using anticoagulant therapy 3, 4.
• The use of reversal agents, such as idarucizumab or andexanet alfa, should be considered in cases of serious bleeding 3.
• The patient should be closely monitored for signs of bleeding, such as bruising or bleeding gums, and should be instructed to report any bleeding episodes to their healthcare provider immediately.