Heparin in acute stroke with atrial fibrillation - Clinical relevance of very early treatment

Background: The risk-benefit ratio of early vs late heparinization for acut e 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 v alues. Delay to the initiation of heparin therapy was less than 6 hours fro m the onset of symptoms in 74 patients and between 6 and 48 hours in 157 pa tients. Functional outcome (Rankin scale) was assessed 9+/-3 (mean +/- SD) days from stroke onset using multivariate analysis and including in the mod el treatment delay, risk factors (eg, age, hypertension, diabetes, hypercho lesterolemia, previous stroke, and heart disease), initial neurological sev erity, and baseline computed tomographic findings (eg, early signs of infar ction and white matter abnormalities). Clinical symptoms on admission (Math ew score) and baseline radiological findings were evaluated in all subjects . The breeding rate was assessed on subsequent computed tomographic (CT) sc ans (obtained 7+/-2 days after stroke). The relationship between APTT ratio s and stroke recurrence or hemorrhagic worsening was also tested. Main Outcome Measures: Functional outcome at hospital discharge and inciden ce of early recurrent strokes and bleeding complications. Results: Mortality (9%), hemorrhagic worsening (3.4%), and early stroke rec urrence (2.1%) occurred in the hospital. Complete recovery was associated w ith age younger than 70 years (odds ratio [OR], 0.21, 95% confidence interv al [CI]x, 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), a nd early heparinization (OR, 1.7; 95% CT, 1.10-2.50), Targeted APTT ratios were achieved at 24 hours in fewer than 50% of patients. Whereas stroke rec urrence 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 non valvular atrial fibrillation is not endorsed by the initial severity of sym ptoms or the early signs of infarction on CT scan. Functional recovery is i mproved the sooner heparin is administered. These findings suggest that hep arin also has therapeutic properties. However, close APTT monitoring is war ranted to lessen the incidence of untoward complications.