Evidence tipping against stroke thrombolysis in patients on warfarin

By Eleanor McDermid

Subtherapeutic warfarin may be harmful in patients undergoing intravenous thrombolysis for stroke, say the authors of a single-center study and meta-analysis.

The single-center study involved 548 stroke patients, of whom 15 were taking warfarin but underwent thrombolysis anyway because their international normalized ratios (INRs) were no higher than 1.7 (in line with US guidelines) and they had no other contraindications.

Patients taking warfarin had a significantly higher rate of symptomatic intracranial hemorrhage than other patients, at 20.0% versus 6.0% according to the National Institute of Neurological Disorders and Stroke (NINDS) definition (any hemorrhage with ≥1 point increase on the National Institutes of Health Stroke Scale [NIHSS]).

This fourfold risk increase persisted after accounting for confounders, report Stefan Kiechl (Medical University Innsbruck, Innsbruck, Austria) and team.

There was also a difference in rates when defined by the more stringent Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) criteria (parenchymal cerebral hemorrhage plus ≥4 point NIHSS increase), at 13.3% versus 4.4%, but this was not statistically significant.

The findings are in line with those of some, but not all, previous studies. But in an editorial accompanying the study in Neurology, Judith Harrer (Caritas Medical Center Saarbrücken, Germany) and Raymond Seet (National University of Singapore) say: "This is not just another single-center study, given that this report provides the first meta-analysis on this issue."

However, they note that the researchers' single-center study included a very small number of patients on warfarin, a drawback that, they say, "cannot simply be overcome by the addition of a meta-analysis."

The meta-analysis highlights the conflicting findings that have so far emerged. It includes an extra eight studies, to give a total of 4856 patients, 284 of whom were taking warfarin. Overall, subtherapeutic warfarin was associated with a doubled risk for symptomatic intracranial hemorrhage, but there was significant heterogeneity among the studies.

Four studies found a significantly increased bleeding risk and five found none. The studies also used different definitions of symptomatic intracranial hemorrhage, with two not stating a definition.

But as the overall findings support the possibility of an increased bleeding risk in patients with warfarin, Harrer and Seet say that, "clearly, the decision for [intravenous] thrombolysis needs to be taken with caution in these patients."

They add: "Specific precautionary measures need to be applied for early recognition of bleeding complications and their prompt treatment."

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