Patients who suffer cardioembolic strokes routinely receive anticoagulation therapy after the acute phase to prevent stroke reoccurrence. Anticoagulation during the acute phase is not recommended, yet physicians often administer heparin or enoxaparin as a bridging strategy to cover the several days it takes for patients to achieve a therapeutic international normalized ratio with warfarin. Hallevi and colleagues examined how these bridging strategies affected outcomes in cardioembolic stroke patients.
The researchers did a retrospective review of all patients (N = 204) admitted to their stroke center from April 2004 through June 2006 with a diagnosis of cardioembolic stroke and who didn't receive thrombolytic therapy. Patients were divided into five groups based on the treatment strategy used: no treatment (n = 8), aspirin only (n = 88), aspirin followed by warfarin (n = 35), IV heparin during the acute phase followed by warfarin (n = 44), and enoxaparin combined with warfarin (n = 29). The treating physician determined which strategy to use based on clinical judgment and personal preference.
Primary end points were serious bleeding, either systemic or a grade 2 parenchymal hematoma (PH2; a dense hematoma of more than 30% of infarct volume and having a mass effect), and stroke reoccurrence before discharge from the hospital. Secondary end points included discharge with good outcome, stroke progression, and in-hospital mortality.
The most common serious adverse event was stroke progression (n = 11), with all but one case occurring in the aspirin-only group. Though patients in this group were 12.5 times more likely to have stroke progression than those in the anticoagulation groups, the higher incidence of progression may be related to the fact that patients in the aspirin-only group had more extensive infarcts at baseline rather than to the treatment strategy used.
Twenty patients experienced benign hemorrhagic transformations, defined as small petechial hematomas of less than 30% of infarct volume and having no mass effect, an asymptomatic problem not uncommon in cardioembolic stroke patients. Three patients experienced PH2; all three received enoxaparin combined with warfarin. These hemorrhagic transformations occurred in a bimodal distribution, a pattern that the authors contend hadn't been documented prior to this study. Ninety-five percent of the benign hematomas occurred in the first three days after the stroke and all three of the PH2s occurred nine to 12 days after the stroke. Despite the small number of cases, the clustering of PH2s in one treatment group suggests, the authors said, a "pathophysiological link" between PH2 and enoxaparin bridging.
The only other serious adverse events were two cases of systemic bleeding, both in the heparin group. Overall, it was found that patients taking anticoagulation therapy were 2.4 times more likely to have a positive outcome than those receiving aspirin only or no treatment.
The authors noted a number of limitations, including the study's retrospective design without randomization, its lack of long-term follow-up, differences in stroke severity among groups, and the possibility that asymptomatic hematomas were missed because routine computed tomographic scans weren't done on anticoagulated patients.
Hallevi and colleagues concluded that in cardioembolic stroke patients, it appears to be safe to start warfarin therapy at any time after admission, but bridging with heparin or enoxaparin carries a high risk of serious bleeding. However, considering the limitations of the study, they recommended that their results be used only to generate hypotheses until further prospective research can be done.
Karen Roush, MSN, RN, FNP-BC