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Warfarin treatment not tied to higher risk of tPA-associated intracranial hemorrhage in stroke patients

NEW YORK (Reuters Health) – Patients receiving warfarin do not face an increased risk of intracranial hemorrhage when their acute ischemic stroke is treated with intravenous tissue plasminogen activator (tPA), according to a report in the June 27 issue of JAMA.

Although the package insert contraindicates the use of tPA in patients receiving warfarin, current guidelines of the American Heart Association/American Stroke Association (AHA/ASA) allow use of intravenous tPA in warfarin-treated patients whose International Normalized Ratio (INR) is 1.7 or lower.

Dr. Eric D. Peterson from Duke Clinical Research Institute in Durham, North Carolina, and colleagues used the AHA Get With The Guidelines-Stroke Registry to evaluate the association of warfarin treatment and symptomatic intracranial hemorrhage (sICH) among patients with stroke receiving intravenous tPA in routine clinical practice.

The study included more than 23,000 patients, 7.7% of whom were taking warfarin prior to admission. Almost 15% (269/1,802) of warfarin-treated patients presented with INRs between 1.5 and 1.7.

Although warfarin-treated patients had a higher unadjusted rate of sICH (5.7%) than did non-warfarin-treated patients (4.6%), warfarin use was not an independent predictor of sICH risk after adjustment for clinical baseline factors — even in the subgroups of patients with INRs between 1.5 and 1.7 and with INRs of 2.0 or lower.

Moreover, after adjustment, INR was not statistically significantly associated with sICH.

As for secondary outcomes, there was no significant difference between patients receiving warfarin and those not receiving warfarin in the rates of life-threatening or serious systemic hemorrhage, any tPA complication, or in-hospital mortality after multivariable adjustment.

Among survivors, there was no significant difference in rates of discharge to a rehabilitation facility, but warfarin-treated patients were more likely than non-warfarin-treated patients to be discharged to a skilled nursing facility.

Based on the AHA/ASA guidelines, 48.6% (1,729/3,554) of patients receiving warfarin who were otherwise eligible did not receive tPA treatment for their acute ischemic stroke.

“These data provide empirical support of current AHA/ASA guideline recommendations and may help support future stroke quality improvement efforts,” the researchers conclude.

“Considering that intravenous tPA remains substantially underutilized in the United States for patients with stroke, with few if any alternate therapies, medical professionals should ensure that eligible patients receive this important therapy,” writes Dr. Mark J. Alberts, of Northwestern University Feinberg School of Medicine in Chicago, in a related editorial.

“(This study) is a positive step in that direction,” he concludes, “providing evidence that patients taking warfarin with INRs of 1.7 or lower can be treated without experiencing a significantly increased risk of sICH. The real risk is in not treating otherwise eligible patients, who may then have prolonged morbidity from their stroke.”


JAMA 2012;307:2600-2608.

JAMA 2012;307:2637-2639.