Using enoxaparin or heparin to bridge long-term anticoagulation therapy with warfarin for secondary stroke prevention has been associated with a high risk for serious bleeding in patients with cardioembolic stroke (CES). A retrospective study of 204 CES patients showed that only those who received bridging with enoxaparin went on to have symptomatic intracranial bleeding. Similarly, all CES cases with systemic bleeding were treated with intravenous heparin.
"Our study suggests doctors should think twice before using enoxaparin, or intravenous heparin for that matter, to bridge anticoagulation therapy with warfarin in patients with cardioembolic stroke," principal investigator Hen Hallevi, MD, from the University of Texas Health Science Center at Houston, told Medscape Neurology & Neurosurgery.
While it is widely acknowledged that CES patients require long-term anticoagulation, the issue of when and how to initiate it remains a clinical dilemma, said Dr. Hallevi.
Routinely bridging CES patients in the acute phase with enoxaparin or heparin until warfarin therapy begins to work is a widespread practice, but one that is not supported by the literature or current guidelines, he said.
He added that the current study was initiated based on anecdotal observations that CES patients tend to have more intracranial and systemic bleeding, also described as hemorrhagic transformation, than other types of stroke patients.
To examine possible explanations for this phenomenon, the researchers looked at the type of treatment administered to CES patients who were admitted to a single stroke center between April 1, 2004 and June 30, 2006 and who were not treated with tissue plasminogen activator.
Patients were categorized into one of 5 possible treatment groups. These included no treatment, aspirin only, aspirin followed by warfarin, intravenous heparin in the acute phase followed by warfarin, and full-dose enoxaparin combined with warfarin.
The study's primary outcomes included serious bleeding (defined as a parenchymal hematoma, grade 2, or systemic bleeding) and stroke recurrence during hospital stay.
Secondary end points included discharge with a favorable outcome (modified Rankin Scale score of 0 to 3), stroke progression, and in-hospital mortality.
All Intracranial Hemorrhage Occurred in a Single Group
Of the total study group, 8 subjects received no anticoagulation, 88 received aspirin alone, 35 were treated with aspirin followed by warfarin, 44 received intravenous heparin followed by warfarin, and 29 received full-dose enoxaparin combined with warfarin.
Hemorrhagic transformation occurred in 23 (11%) patients. Of these cases, 3 were symptomatic. Systemic bleeding occurred in 2 patients, who were both taking heparin.
"We found that all of the hemorrhage cases were in 1 group - those who were bridged with enoxaparin," said Dr. Hallevi. "When you think about it, this is really not surprising, because the good thing, as well as the bad thing, about this drug is that it does exactly what it is supposed to do, it fully anticoagulates," he said.
"We believe the infarct damages the small and medium-sized vessels, which are later reperfused and tend to leak blood. But the difference between this patient group and patients with other types of stroke is that those with cardioembolic stroke get anticoagulated really quickly, which promotes bleeding," he added.
Stroke progression occurred in 11 (5%) of patients and was significantly associated with poor outcome. All except 1 of these cases occurred in the aspirin-only group. In fact, the analysis revealed that patients receiving aspirin alone were 12.5 times more likely to experience progressive stroke compared with individuals on other types of anticoagulation. This finding, said Dr. Hallevi, suggests aspirin may not be as potent as other forms of anticoagulation therapies.
Despite these findings, Dr. Hallevi, cautioned that the retrospective nature of the study cannot prove causality. Nevertheless, he added, clinicians treating CES patients may want to consider these findings before opting for anticoagulation with enoxaparin or heparin.
Arch Neurol. Published online July 14, 2008. Abstract