Efficacy Outcomes

In the routine clinical settings of the DMP, lepirudin-treated patients with isolated HIT and HIT with thrombosis had the lowest incidence of all clinical endpoints reported with any agent. The incidence of the combined clinical endpoint in the 496 patients with HIT and thrombosis was 21.9%: 26 patients (5.2%) experienced new thrombosis, 29 (5.8%) underwent limb amputation, and 54 patients (10.9%) died. The most common cause of death was multiorgan failure (23/54 patients [42.6%]), emphasizing the serious underlying medical condition of these patients. The incidence of new thrombosis in this study (5.2%) was lower than that observed in the HAT-1 and -2 meta-analysis (10.1%). This may be due to physicians' increased clinical experience with lepirudin, as illustrated by the decision to begin lepirudin treatment immediately upon clinical diagnosis of HIT, thereby improving efficacy and safety outcomes.

The combined endpoint of new thrombosis, limb amputation, and death occurred in 96 (15.7%) of the 612 patients with isolated HIT; 13 patients (2.1%) experienced new thrombosis, 8 (1.3%) underwent limb amputation, and 75 patients (12.3%) died. As seen in the group of patients with HIT plus thrombosis, the largest cause of death in this group was multiorgan failure (39/75 patients, 52.0%).

The overall mortality rate due to new thrombosis in the group of 1108 patients treated with regimen Al or B (thus, excluding patients receiving "miscellaneous" treatments) (Table 5) was low (15 patients, or 1.4%). Efficacy variables in the DMP were even more favorable than those seen in the meta-analyses of the HAT studies. This DMP thus confirms the efficacy of lepirudin in routine clinical practice for both the prophylaxis and the treatment of thromboembolism in patients with HIT.

There were no differences in the mean infusion rates in patients with HIT and thrombosis (0.12 mg/kg/h) and those with isolated HIT (0.11 mg/kg/h) in the DMP. As lepirudin dose is adjusted based on aPTT, the major difference between the two regimens is the initial bolus in HIT patients with acute thrombosis. However, as discussed earlier, in the view of the author the bolus should be avoided in most situations to prevent overdosing.

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