A study in the June 27 edition of JAMA reports that patients treated with warfarin (with an INR 1.7 or less) who had an acute ischemic stroke were not linked to a higher risk of symptomatic intracranial hemorrhage when using intravenous tissue plasminogen activator (tPA) compared with patients who were not treated with warfarin as standard treatment.

The study’s background information says: “Intravenous tissue plasminogen activator is currently the only effective treatment to improve outcomes for acute ischemic stroke; however, treatment with intravenous tPA carries the risk of symptomatic intracranial hemorrhage (sICH). Of patients who receive intravenous tPA for stroke, 2.4% to 8.8% experience this potentially life-threatening complication. Although current guidelines endorse administering intravenous tPA to warfarin-treated patients if their international normalized ratio (INR) is 1.7 or lower, there are few data on safety of intravenous tPA in warfarin-treated patients in clinical practice.”

Some researchers were concerned about administering intravenous tPA to stroke patients on warfarin therapy without safety data.

Ying Xian, M.D., Ph.D., from the Duke Clinical Research Institute in Durham, N.C., and his team examined the link between warfarin treatment and sICH in stroke patients who received intravenous tPA as their standard clinical treatment in 23,437 patients with ischemic stroke who had an INR of 1.7 or lower between April 2009 and 2011. The data was obtained from the American Heart Association Get With The Guidelines-Stroke Registry.

1,802 (7.7%) participating patients on intravenous tPA took warfarin before being admitted. Those treated on warfarin tended to be older patients, with more co-morbid conditions, who had more severe strokes and were more likely to be female.

Patients on warfarin’s INR levels at baseline (1.20) were on average higher than those who did not receive warfarin (1.00). 1,107 patients in total (4.7%) of patients developed sICH after receiving tPA intravenously. The team observed that those on warfarin had a higher overall unadjusted rate of sICH (5.7%) compared with those who did not receive warfarin (4.6%). The team points out that using warfarin was not an independent predictor of sICH risk after risk adjustment.

The researchers write:

“The rates of life-threatening or serious systemic hemorrhage were similar in both groups (0.9 percent vs. 0.9 percent), although higher unadjusted rates of any tPA complication (10.6 percent vs. 8.4 percent) and mortality (11.4 percent vs. 7.9 percent) were observed in warfarin-treated patients. However, after multivariable adjustment, warfarin use was not associated with life-threatening or serious systemic hemorrhage, any tPA complication, or in-hospital mortality.”

The team also discovered that the level of anticoagulation had no statistically important link to sICH risk in patients on warfarin therapy with INRs of 1.7 or lower.

The team concludes writing they “found the potential for substantial undertreatment, because up to 50 percent of warfarin-treated patients who might have been eligible for reperfusion therapy did not receive intravenous tPA. These data provide empirical support of current American Heart Association/American Stroke Association guideline recommendations and may help support future stroke quality improvement efforts.”

Written by Petra Rattue