For patients with cardioembolic stroke, “bridging” therapy with either enoxaparin or heparin until long-term warfarin treatment takes effect raised the risk of serious bleeding, compared with immediately commencing warfarin, a study shows.
In contrast, initiating warfarin shortly after cardioembolic stroke was found to be safe in this single-center retrospective review of 204 patients, according to Dr. Hen Hallevi of the University of Texas at Houston and associates (Arch. Neurol. 2008 July 14 [doi:10.1001/archneur.65.9.noc70105]).
Because this study was retrospective and nonrandomized, the results await validation; they should be viewed as “hypothesis-generating,” and should be interpreted with caution, they noted.
Currently no consensus exists on when and how to institute long-term anticoagulation for secondary stroke prevention in these patients. “Bridging” with enoxaparin or heparin is common practice even though it is not endorsed in published guidelines, the investigators said.
Many clinicians also defer initiating warfarin for fear of precipitating a hypercoagulable state, which “may occur when warfarin is initiated without heparin and may lead to abnormal clotting and skin necrosis,” they said. However, this is an uncommon occurrence in clinical practice, and is usually associated with protein C deficiency, they added.
In this study, all cases of cardioembolic stroke between April 2004 and July 2006 were reviewed. The decisions of whether to use bridging and, if so, whether to use enoxaparin or heparin were “based on clinical judgment and personal preference of the treating physician.”
Thirty-five patients were given warfarin immediately, without any bridging. Forty-four received heparin bridging, and 29 received enoxaparin bridging. Another 8 patients received no anticoagulation therapy, and 88 received aspirin only.
The patients who received no anticoagulation or only aspirin fared poorly and were 12 times more likely to experience stroke progression than those in the other treatment groups.
Heparin bridging was significantly more likely to cause systemic bleeding, and enoxaparin bridging was significantly more likely to cause grade 2 parenchymal hematoma, compared with immediate warfarin.
There were no episodes of skin necrosis in the warfarin group, supporting the observation that this complication is very uncommon in clinical practice and that bridging specifically to prevent skin necrosis is unwarranted, Dr. Hallevi and his associates said
Moreover, there was a clustering of cases of late, symptomatic hemorrhagic transformation “composing an alarming 10%” of the enoxaparin group, with no cases in the warfarin and heparin groups. This suggests a pathophysiologic link between enoxaparin and hemorrhagic transformation, they added.
“Warfarin treatment appears to be safe and can be started at any point during the hospital stay, along with deep vein thrombosis prophylaxis. [In contrast], bridging with a full dose of enoxaparin or heparin may carry a high risk of intracranial and systemic bleeding,” the researchers said.