Stroke

The effect of argatroban anticoagulation on stroke in HIT has been retrospectively evaluated using case records from the prospective studies of argatroban in HIT (LaMonte et al., 2004b). Stroke was present at or within 37 days of study entry in 30 (3.1%) of 960 patients overall. Compared with control therapy, argatroban significantly reduced the risk of new stroke (odds ratio = 0.31, 95% CI, 0.10-0.96, p = 0.041) and stroke-associated mortality (odds ratio = 0.18, 95% CI, 0.03-0.92, p = 0.039), without increasing intracranial hemorrhage. Of 35 strokes, 33 (94%) were ischemic, with one hemorrhagic stroke in each group. Stroke occurred most often in females, in patients with more severe thrombocytopenia, and within 2 wk of HIT presentation.

In a randomized, double-blind clinical study of patients treated with argatroban versus placebo within 12 h of ischemic stroke onset, there were no significant between-group differences in intracranial hemorrhage or major bleeding rates (LaMonte et al., 2004a). In an ongoing open-label, dose escalation study of argatroban in combination with recombinant tissue plasminogen activator in acute stroke, safety was within acceptable limits in the first treated cohort, and efficacy for producing fast, complete recanalization was promising (Sugg et al., 2006). Although not conducted in patients with HIT, these studies further support the safety of argatroban anticoagulation in patients with stroke. Argatroban is approved for use in nonlacunar stroke in Japan and Korea.

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