What is the recommended treatment regimen for patients with elevated high-sensitivity C-reactive protein (hsCRP) after stroke or transient ischemic attack (TIA)?

Treatment Recommendations for Patients with Elevated hsCRP After Stroke or TIA

For patients with elevated high-sensitivity C-reactive protein (hsCRP) after stroke or transient ischemic attack (TIA), standard secondary prevention with antiplatelet therapy, statins, blood pressure management, and diabetes control is recommended, as colchicine has not shown benefit in reducing subsequent stroke risk despite its anti-inflammatory properties.

Antiplatelet Therapy

• For noncardioembolic stroke/TIA patients with elevated hsCRP:

  • Daily long-term antiplatelet therapy should be prescribed immediately 1
  • The combination of aspirin (50mg) and sustained-release dipyridamole (200mg twice daily) is a reasonable first-line option 1
  • Clopidogrel (75mg daily) may be slightly more effective than aspirin alone 1
  • Aspirin 160-325mg should be given within 24-48 hours after stroke onset (delayed 24 hours if treated with IV alteplase) 2

• For cardioembolic stroke/TIA patients:

  • Long-term oral anticoagulation with target INR 2.5 (range 2.0-3.0) is recommended for those with atrial fibrillation 1
  • For patients with mechanical heart valves, warfarin is recommended over DOACs 1
  • For patients with non-valvular AF, DOACs (dabigatran, rivaroxaban, apixaban, edoxaban) are recommended over warfarin 1

Statin Therapy

• Statin therapy with intensive lipid-lowering effects is recommended for patients with ischemic stroke/TIA who have evidence of atherosclerosis 1
• Target a reduction of at least 50% in LDL-C or a target LDL-C level of <70 mg/dL to obtain maximum benefit 1
• Treatment with a statin is recommended for most people after atherothromboembolic TIA regardless of baseline cholesterol levels 1

Blood Pressure Management

• Blood pressure should be reduced to less than 140/90 mmHg or less than 130/80 mmHg for diabetics 1
• An ACE inhibitor alone or in combination with a diuretic, or an angiotensin receptor blocker is recommended 1
• For normotensive patients, consideration should be given to lowering blood pressure by approximately 9/4 mmHg provided there is no high-grade carotid stenosis 1

Diabetes Management

• Fasting blood glucose levels less than 126mg/dl (7mmol/L) are recommended 1
• Diet, regular exercise, and oral hypoglycemics or insulin should be prescribed as needed to control diabetes 1
• Use existing guidelines for glycemic control and BP targets in patients with diabetes who have had a stroke or TIA 1

Anti-inflammatory Therapy for Elevated hsCRP

Despite the association between elevated hsCRP and increased risk of recurrent events 3, specific anti-inflammatory treatments targeting hsCRP have not shown benefit:

• The recent CHANCE-3 trial (2024) found that low-dose colchicine did not reduce the risk of subsequent stroke within 90 days compared to placebo among patients with acute non-cardioembolic minor-to-moderate ischemic stroke or TIA and elevated hsCRP (≥2 mg/L) 4
• Stroke occurred in 6.3% of patients in the colchicine group vs. 6.5% in the placebo group (hazard ratio 0.98,95% CI 0.83-1.16) 4
• Earlier pilot studies showed mixed results regarding colchicine's ability to reduce hsCRP levels after stroke 5, 6

Lifestyle Modifications

• Smoking cessation should be strongly encouraged 1
• Weight reduction for patients with BMI >25 (especially >30) 1
• Regular physical activity (at least 10 minutes of exercise 3-4 times/week) 1
• Salt restriction and appropriate dietary modifications 1

Monitoring and Follow-up

• Regular monitoring of hsCRP levels may help identify high-risk patients who need more aggressive prevention strategies 3
• Patients with hsCRP >4.1 mg/L have been shown to have a higher risk of recurrent events (HR 2.81,95% CI 1.12-7.10) 3

Pitfalls and Caveats

• While elevated hsCRP is a predictor of recurrent events, there is currently no specific anti-inflammatory treatment proven to reduce this risk
• Do not delay standard secondary prevention measures while focusing on hsCRP levels
• Colchicine can cause gastrointestinal side effects, particularly diarrhea 6
• Hormone replacement therapy should be avoided for secondary stroke prevention in postmenopausal women 1

Despite the association between inflammation and stroke risk, the focus of treatment should remain on established secondary prevention strategies rather than specific anti-inflammatory treatments targeting elevated hsCRP.