What is the goal low-density lipoprotein (LDL) level for patients who have had a stroke?

Goal LDL in Stroke Patients

For patients with ischemic stroke or TIA and atherosclerotic disease (intracranial, carotid, aortic, or coronary), the target LDL-C should be <70 mg/dL to reduce the risk of major cardiovascular events. 1

Evidence-Based LDL Targets by Patient Category

Primary Recommendation

• LDL-C <70 mg/dL is the recommended target for patients with ischemic stroke and atherosclerotic disease 1
• This target is supported by the most recent guidelines from both the American Heart Association/American Stroke Association (2021) and the World Stroke Organization (2023)

Patient-Specific Targets

1. Patients with ischemic stroke with atherosclerotic disease:

   • Target: LDL-C <70 mg/dL 1
   • Medication: High-intensity statin (atorvastatin 80 mg) plus ezetimibe if needed
   • Evidence: TST trial showed targeting LDL-C <70 mg/dL was superior to 90-110 mg/dL for preventing major cardiovascular events 2

2. Patients with ischemic stroke without known coronary heart disease or cardiac embolism:

   • If LDL-C >100 mg/dL: Atorvastatin 80 mg daily 1
   • Target: Reduction to <70 mg/dL is reasonable 1

3. Very high-risk patients (stroke plus another major ASCVD or multiple high-risk conditions):

   • Target: LDL-C <70 mg/dL 1
   • If target not achieved with maximally tolerated statin and ezetimibe: Consider PCSK9 inhibitor 1

Treatment Algorithm

1. First-line therapy:

   • High-intensity statin (atorvastatin 80 mg daily) 1, 3
   • Monitor LDL-C levels 4-12 weeks after initiation 1

2. If target LDL-C <70 mg/dL not achieved:

   • Add ezetimibe 1
   • Monitor LDL-C again after 4-12 weeks

3. If still not at goal:

   • For very high-risk patients: Consider adding PCSK9 inhibitor 1
   • Very high risk defined as stroke plus another major ASCVD event or stroke plus multiple high-risk conditions (age ≥65, diabetes, hypertension, etc.) 1

4. Monitoring schedule:

   • Check lipid levels 4-12 weeks after statin initiation or dose adjustment
   • Then every 3-12 months based on adherence and safety concerns 1

Clinical Evidence Supporting <70 mg/dL Target

The most compelling evidence comes from the TST (Treat Stroke to Target) trial, which directly compared two LDL-C targets in stroke patients:

• Patients with LDL-C <70 mg/dL had a 22% reduction in major cardiovascular events compared to those with LDL-C 90-110 mg/dL 2
• In the French cohort with 5.3 years follow-up, targeting LDL-C <70 mg/dL reduced major vascular events by 26% (NNT of 30) 4
• No significant increase in intracranial hemorrhage was observed with lower LDL-C levels 4, 2

Important Considerations and Pitfalls

1. Safety concerns:

   • Very low LDL-C levels (<70 mg/dL) have not shown increased risk of neurocognitive impairment 1
   • Evidence regarding hemorrhagic stroke risk is mixed, but recent large trials show no significant increase in hemorrhagic stroke with aggressive LDL-C lowering 1, 4, 5

2. Common pitfalls:

   • Inadequate dosing of statins (use high-intensity statins)
   • Failure to add ezetimibe when statin alone is insufficient
   • Premature discontinuation due to mild side effects
   • Inadequate monitoring of LDL-C levels

3. Special populations:

   • Even patients with baseline LDL-C <70 mg/dL benefit from statin therapy after stroke 5
   • Statin treatment in patients with already low LDL-C (<70 mg/dL) was associated with reduced 3-month composite outcomes without increasing hemorrhagic stroke risk 5

The evidence strongly supports aggressive LDL-C lowering to <70 mg/dL in patients with ischemic stroke, particularly those with evidence of atherosclerotic disease, to reduce the risk of recurrent stroke and other cardiovascular events.