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Published Online
on October 13, 2005

Stroke. 2005
Published online before print October 13, 2005, doi: 10.1161/01.STR.0000185730.50480.e7
A more recent version of this article appeared on November 1, 2005
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Submitted on June 12, 2005
Revised on July 13, 2005
Accepted on August 4, 2005

Intravenous Heparin Started Within the First 3 Hours After Onset of Symptoms as a Treatment for Acute Nonlacunar Hemispheric Cerebral Infarctions

Massimo Camerlingo MD*; Pietro Salvi MD; Giorgio Belloni MD; Tiziano Gamba MD; Bruno Mario Cesana MD; and Angelo Mamoli MD

From the Second Neurological Unit and the Neuroradiological Unit (M.C., G.B., A.M.), Ospedali Riuniti, Bergamo, Italy; the Rehabilitation Unit (P.S.), Clinica Quarenghi, S. Pellegrino Terme, Bergamo, Italy; general practitioner (T.G.), Bergamo, Italy; and the Epidemiological Laboratory (B.M.C.), University of Milan, IRCCS Ospedale Maggiore, Milan, Italy.

* To whom correspondence should be addressed. E-mail: massimo.camerlingo{at}virgilio.it.

Background and Purpose--Heparin is widely used for acute stroke to prevent thrombus propagation and/or multiple emboli generation, although there is, as yet, no demonstrated efficacy. However, all of the available clinical studies allowed long intervals from stroke to treatment. The purpose of this study was to try an intravenous regimen of unfractionated heparin the acute cerebral infarction starting treatment within the first 3 hours of the onset of symptoms.

Methods--The study was an outcome evaluator-blind design trial. Patients had to display signs of a nonlacunar hemispheric infarction. Selected patients were randomly allocated to receive intravenous heparin sodium or saline. Heparin was infused at a rate to maintain activated partial thromboplastin time ratio 2.0 to 2.5 x control for 5 days. The primary end point was recovery of a modified Rankin score zero to 2 at 90 days of stroke at phone interview by a single physician blind to treatment. Safety end points were death, symptomatic intracranial hemorrhages, and major extracranial bleedings by 90 days of stroke.

Results--A total of 418 stroke patients were included. In the heparin group, there were more self-independent patients (38.9% versus 28.6%; P=0.025). In addition, in the same group, there were fewer deaths (16.8% versus 21.9%; P=0.189), more symptomatic brain hemorrhages (6.2% versus 1.4%; P=0.008), and more major extracerebral bleedings (2.9% versus 1.4%; P=0.491).

Conclusions--Intravenous heparin sodium could be of help in the earliest treatment of acute nonlacunar hemispheric cerebral infarction, even keeping into account an increased frequency of intracranial symptomatic brain hemorrhages.


Key words: anticoagulation • cerebral ischemia • heparin • stroke




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