What is the recommended treatment for a patient with a late‑subacute cerebral infarction (7–14 days after onset)?

Treatment of Late Subacute Cerebral Infarction (7–14 Days Post-Onset)

For patients with late subacute cerebral infarction (7–14 days after onset), the primary treatment focus is secondary stroke prevention through antiplatelet therapy, statin therapy, blood pressure management, and—if atrial fibrillation is present—carefully timed initiation of oral anticoagulation based on stroke severity. 1, 2

Antiplatelet Therapy

• Aspirin (75–162 mg daily) should be continued or initiated for long-term secondary prevention in all patients without contraindications. 2
• If aspirin was started within 48 hours of stroke onset (as recommended), it should be continued throughout the subacute period and indefinitely. 1, 2
• Alternative antiplatelet regimens include clopidogrel 75 mg daily or the combination of aspirin plus extended-release dipyridamole if aspirin alone is not tolerated or contraindicated. 2, 3

Statin Therapy

• High-intensity statin therapy should be initiated or continued in most patients with ischemic stroke to reduce recurrent vascular events. 3
• This recommendation applies regardless of baseline cholesterol levels, as statins provide pleiotropic vascular protective effects beyond lipid lowering. 3

Blood Pressure Management

• Antihypertensive therapy should be initiated or resumed during the subacute period, targeting blood pressure <140/90 mmHg for most patients. 3
• The initial permissive hypertension strategy used in the hyperacute phase (first 24–48 hours) should transition to active blood pressure control by 7–14 days post-stroke. 2, 3

Anticoagulation for Atrial Fibrillation

Timing Based on Stroke Severity

For patients with atrial fibrillation, the timing of anticoagulation initiation during the 7–14 day window depends critically on stroke severity:

• For mild stroke (NIHSS <8): Anticoagulation should already have been started by day 3, so by days 7–14 the patient should be on therapeutic anticoagulation. 1, 4
• For moderate stroke (NIHSS 8–15): Initiate oral anticoagulation between days 6–8 after confirming absence of hemorrhagic transformation on repeat brain imaging. 1, 4
• For severe stroke (NIHSS ≥16 or large territorial infarct): Delay anticoagulation until days 12–14 after repeat imaging excludes hemorrhagic transformation. 1, 4

Critical Safety Measures

• Repeat brain imaging (CT or MRI) is mandatory before starting anticoagulation in moderate-to-severe strokes to exclude hemorrhagic transformation, which occurs in 6–21% of patients. 4
• Direct oral anticoagulants (DOACs: apixaban, dabigatran, edoxaban, or rivaroxaban) are strongly preferred over warfarin, as they reduce intracranial hemorrhage risk by approximately 51–56%. 4
• Heparin "bridging" therapy is contraindicated during the 7–14 day period, as it significantly increases symptomatic intracranial hemorrhage without improving outcomes. 1, 4

Evidence Supporting the 4–14 Day Window

• An observational study of 1,029 patients demonstrated that initiating anticoagulation between 4–14 days after cardioembolic stroke was associated with the best outcomes (hazard ratio 0.53,95% CI 0.30–0.93) compared to earlier or later initiation. 5
• Starting anticoagulation before day 4 increases hemorrhagic risk, while delaying beyond day 14 exposes patients to ongoing recurrent stroke risk of 0.4–1.3% per day. 4, 5

Supportive Care and Complication Prevention

• Venous thromboembolism prophylaxis with intermittent pneumatic compression devices or subcutaneous heparin (if no hemorrhagic transformation) should be continued for immobilized patients. 2
• Nutritional support, physical therapy, occupational therapy, and speech therapy should be actively ongoing during the 7–14 day period. 3
• Monitoring for complications including aspiration pneumonia, urinary tract infection, pressure ulcers, and delirium should continue. 3

Glycemic Control

• For patients with diabetes or stress hyperglycemia, target blood glucose should be 140–180 mg/dL using a basal-bolus insulin regimen with frequent monitoring (minimum four times daily). 2
• Fixed-dose insulin without glucose monitoring is suboptimal and increases hypoglycemia risk, which can worsen neurological outcomes. 2

Common Pitfalls to Avoid

• Do not start anticoagulation in the 7–14 day window without first obtaining repeat brain imaging to exclude hemorrhagic transformation, especially in moderate-to-severe strokes. 4
• Do not use heparin bridging while waiting to start oral anticoagulation—this practice increases bleeding risk without benefit. 1, 4
• Do not delay anticoagulation beyond 14 days in atrial fibrillation patients without a specific contraindication, as recurrent stroke risk remains high (0.4–1.3% per day). 4
• Do not combine antiplatelet therapy with anticoagulation in atrial fibrillation patients unless there is a specific indication (e.g., recent coronary stenting), as this increases bleeding risk. 6

Stroke Etiology Workup

• If not completed during the hyperacute phase, diagnostic evaluation should include carotid imaging (ultrasound or MR angiography), echocardiography (transthoracic ± transesophageal), and prolonged cardiac monitoring (minimum 24-hour Holter) to identify cardioembolic sources. 3, 7
• Identifying atrial fibrillation or other high-risk cardiac sources during this period directly impacts the decision to initiate anticoagulation. 7