Heparin in acute stroke with atrial fibrillation: clinical relevance of very early treatment

Arch Neurol. 1999 Sep;56(9):1098-102. doi: 10.1001/archneur.56.9.1098.


Background: The risk-benefit ratio of early vs late heparinization for acute stroke with nonvalvular atrial fibrillation remains unsettled.

Objective: To clarify the relationship between timing to heparinization and functional outcome in acute cardioembolic stroke.

Design: Consecutive case series.

Setting: Referral center.

Patients: In 231 patients with stroke and nonvalvular atrial fibrillation, intravenous or subcutaneous heparin administered with the goal of achieving an activated partial thromboplastin time (APTT) 1.5 to 2.0 times control values. Delay to the initiation of heparin therapy was less than 6 hours from the onset of symptoms in 74 patients and between 6 and 48 hours in 157 patients. Functional outcome (Rankin scale) was assessed 9 +/- 3 (mean +/- SD) days from stroke onset using multivariate analysis and including in the model treatment delay, risk factors (eg, age, hypertension, diabetes, hypercholesterolemia, previous stroke, and heart disease), initial neurological severity, and baseline computed tomographic findings (eg, early signs of infarction and white matter abnormalities). Clinical symptoms on admission (Mathew score) and baseline radiological findings were evaluated in all subjects. The bleeding rate was assessed on subsequent computed tomographic (CT) scans (obtained 7 +/- 2 days after stroke). The relationship between APTT ratios and stroke recurrence or hemorrhagic worsening was also tested.

Main outcome measures: Functional outcome at hospital discharge and incidence of early recurrent strokes and bleeding complications.

Results: Mortality (9%), hemorrhagic worsening (3.4%), and early stroke recurrence (2.1%) occurred in the hospital. Complete recovery was associated with age younger than 70 years (odds ratio [OR], 0.21; 95% confidence interval [CI], 0.05-0.70), a baseline Mathew score higher than 74 (OR, 11.5; 95% CI, 4.95-26.70), normal baseline CT findings (OR, 8.86; CI, 3.99-19.60), and early heparinization (OR, 1.7; 95% CI, 1.10-2.50). Targeted APTT ratios were achieved at 24 hours in fewer than 50% of patients. Whereas stroke recurrence was associated with lower mean APTT ratios, higher mean APTT ratios were observed in patients with symptomatic bleeding, especially on the day of bleeding. Age, admission stroke severity, blood pressure, and baseline CT findings did not predict hemorrhagic worsening.

Conclusions: Delaying anticoagulation in alert patients with stroke and nonvalvular atrial fibrillation is not endorsed by the initial severity of symptoms or the early signs of infarction on CT scan. Functional recovery is improved the sooner heparin is administered. These findings suggest that heparin also has therapeutic properties. However, close APTT monitoring is warranted to lessen the incidence of untoward complications.

MeSH terms

  • Acute Disease
  • Aged
  • Anticoagulants / administration & dosage*
  • Atrial Fibrillation / complications*
  • Cerebrovascular Disorders / drug therapy*
  • Cerebrovascular Disorders / etiology
  • Drug Administration Schedule
  • Female
  • Heparin / administration & dosage*
  • Humans
  • Intracranial Embolism and Thrombosis / complications*
  • Intracranial Embolism and Thrombosis / etiology
  • Male
  • Middle Aged
  • Odds Ratio
  • Partial Thromboplastin Time
  • Risk Factors
  • Survival Analysis
  • Time Factors
  • Treatment Outcome


  • Anticoagulants
  • Heparin