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Published Online
on January 12, 2006

Stroke. 2006
Published online before print January 12, 2006, doi: 10.1161/01.STR.0000198887.81948.74
A more recent version of this article appeared on February 1, 2006
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*Compound via MeSH
*Substance via MeSH
Medline Plus Health Information
*Atrial Fibrillation
*Blood Thinners
*Stroke
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Right arrow Heparin
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Submitted on April 28, 2005
Revised on September 15, 2005
Accepted on October 11, 2005

Are There Patients With Acute Ischemic Stroke and Atrial Fibrillation That Benefit From Low Molecular Weight Heparin?

Martin J. O’Donnell MB; Eivind Berge MD, PhD*; and Per Morten Sandset MD, PhD

From the Stanford Stroke Center (M.J.O.), Stanford University Medical Center, Palo Alto, Calif; and Department of Hematology (E.B., P.M.S.), Ullevål University Hospital, Oslo, Norway.

* To whom correspondence should be addressed. E-mail: eivind.berge{at}medisin.uio.no.

Background and Purpose--Treatment doses of heparins are not recommended for acute ischemic stroke. Despite this, their use in this setting is widespread. We investigated whether subgroups of patients with acute ischemic stroke and atrial fibrillation, identified by clinical, hemostatic (D-dimer, prothombin fragments1+2 [F1+2], soluble fibrin monomer), or inflammatory (C-reactive protein [CRP]) variables might have a differential response to low molecular weight heparin (LMWH) over aspirin. In addition, we sought to identify factors associated with a poor clinical outcome at 3 months.

Methods--We conducted a post hoc subgroup analysis of a randomized, placebo-controlled, double-blind trial (Heparin in Acute Embolic Stroke Trial) designed to test the hypothesis that treatment doses of LMWH (dalteparin; 100 IU/kg BID) would be superior to aspirin (160 mg per day) in patients with acute ischemic stroke and atrial fibrillation. For the current analysis, 431 participants were included. The primary outcome measure was a poor outcome at 3 months, defined as death or dependency in activities of daily living. Using regression analysis, we determined whether any of the chosen variables were associated with a differential response to dalteparin (treatment interaction) or with poor outcome.

Results--In the multivariable logistic regression model, none of the clinical, hemostatic, or inflammatory variables were associated with a significant treatment interaction. Stroke severity (odds ratio [OR], 1.09 [95% CI, 1.07 to 1.12]), increasing age (OR, 1.09 [CI, 1.05 to 1.14]), CRP level (OR, 1.32 [CI, 1.04 to 1.66]), and F1+2 level (OR, 1.77 [CI, 1.07 to 2.91]) were independently associated with a poor outcome at 3 months.

Conclusions--Our study does not support the use of treatment doses of LMWH in any of the studied subgroups of patients with acute ischemic stroke and atrial fibrillation. Age, stroke severity, CRP, and F1+2 were predictive of poor outcome at 3 months.


Key words: heparin • stroke, ischemic • atrial fibrillation