What is the most appropriate oral antithrombotic therapy for a 68-year-old male with a history of hypertension, hyperlipidemia, type 2 diabetes mellitus, and smoking, presenting with acute ischemic stroke, after receiving fibrinolysis?

From the Guidelines

The most appropriate oral antithrombotic therapy for RS at this time is Aspirin 81 mg daily. This recommendation is based on the patient's clinical presentation of an ischemic stroke with a 50% stenosis in the left anterior cerebral artery. After receiving fibrinolysis, single antiplatelet therapy with low-dose aspirin is the standard approach for secondary stroke prevention, as supported by guidelines from the American Heart Association/American Stroke Association 1. Aspirin works by inhibiting platelet aggregation through the irreversible inhibition of cyclooxygenase-1, reducing the risk of recurrent stroke. Some key points to consider in this decision include:

• The use of aspirin in acute ischemic stroke has been extensively tested, showing a modest but statistically significant benefit in preventing recurrent events 1.
• Dual antiplatelet therapy combinations, such as aspirin plus ticagrelor or cilostazol, would increase bleeding risk without clear benefit in this scenario.
• Rivaroxaban, an anticoagulant, is not indicated for atherosclerotic stroke but rather for cardioembolic strokes, such as those associated with atrial fibrillation.
• The lower dose of 81 mg aspirin provides sufficient antiplatelet effect while minimizing bleeding risks, particularly important in this 68-year-old patient with multiple vascular risk factors. The patient should continue this therapy long-term along with aggressive management of his other stroke risk factors, including hypertension, hyperlipidemia, diabetes, and smoking cessation.

From the FDA Drug Label

The efficacy and safety of XARELTO 2.5 mg orally twice daily versus placebo on a background of aspirin 100 mg once daily in patients with PAD were evaluated in the COMPASS study All patients received aspirin 100 mg once daily as background therapy XARELTO 2.5 mg twice daily was superior to placebo in reducing the rate of the primary composite outcome of myocardial infarction, ischemic stroke, cardiovascular death, acute limb ischemia (ALI), and major amputation of a vascular etiology.

The most appropriate oral antithrombotic therapy to recommend for RS at this time is Aspirin 81 mg daily or Aspirin 325 mg daily plus another antiplatelet, but the provided label does not directly support the use of Aspirin 325 mg daily plus ticagrelor 90 mg twice daily, Aspirin 325 mg daily plus cilostazol 100 mg twice daily, or Rivaroxaban 15 mg daily for this specific patient population. However, it does support the use of Rivaroxaban in patients with PAD, and RS has a history of smoking and PAD-like conditions (e.g. 50% stenosis in the left anterior cerebral artery), but the label does not directly address the use of rivaroxaban for secondary stroke prevention in this context.

• Key points:
  • Aspirin is used as background therapy in the studies
  • Rivaroxaban is used for reduction of risk of major thrombotic vascular events in patients with PAD
  • The label does not directly address the use of rivaroxaban for secondary stroke prevention in this context 2

From the Research

Antithrombotic Therapy for Secondary Stroke Prevention

The patient, RS, has a history of hypertension, hyperlipidemia, type 2 diabetes mellitus, and smoking, and has been diagnosed with an acute ischemic stroke. The National Institutes of Health Stroke Scale score is 15, and a computed tomography (CT) scan of the head showed no acute hemorrhage.

• The patient received fibrinolysis, and the team is discussing antithrombotic therapy for secondary stroke prevention.
• According to the study 3, the combination of ticagrelor and aspirin has been shown to be effective in preventing stroke or death within 30 days in patients with mild-to-moderate acute noncardioembolic ischemic stroke or transient ischemic attack (TIA).
• The study 3 found that the risk of the composite of stroke or death within 30 days was lower with ticagrelor-aspirin than with aspirin alone, but the incidence of disability did not differ significantly between the two groups.
• However, severe bleeding was more frequent with ticagrelor.
• Another study 4 suggests that aspirin is used for secondary prevention in patients with a low risk of recurrent stroke, while the combination of aspirin and dipyridamole or clopidogrel is recommended in patients with a higher risk.
• There is no evidence to suggest that rivaroxaban or cilostazol would be more effective than aspirin and ticagrelor in this patient.

Recommended Antithrombotic Therapy

Based on the available evidence, the most appropriate oral antithrombotic therapy to recommend for RS at this time would be:

• Aspirin 325 mg daily plus ticagrelor 90 mg twice daily, as this combination has been shown to be effective in preventing stroke or death within 30 days in patients with mild-to-moderate acute noncardioembolic ischemic stroke or TIA 3.

Considerations

It is essential to weigh the benefits and risks of antithrombotic therapy in this patient, considering his history of hypertension, hyperlipidemia, type 2 diabetes mellitus, and smoking, as well as the results of the CT scan and the National Institutes of Health Stroke Scale score. The patient's bleeding risk should also be assessed, as severe bleeding was more frequent with ticagrelor in the study 3.