This meta-analysis focuses on 2 prospective studies in patients with
heparin-induced
thrombocytopenia (HIT) and thromboembolic complication (TEC) who were treated with
lepirudin (n = 113). Data were compared with those of a historical control group (n = 91). The primary endpoint (combined incidence of death, new TEC, and limb
amputation) occurred in 25
lepirudin-treated patients (22.1%; 95% CI, 14.5%-29.8%): 11 died (9.7%; 95% CI, 4.9%-16.8%), 7 underwent limb
amputation (6.2%; 95% CI, 2.5%-12.3%), and 12 experienced new TEC (10.6%; 95% CI, 5.8%-18.3%). The risk was highest in the period between diagnosis of HIT and the start of
lepirudin therapy (combined event rate per patient day 6.1%). It markedly decreased to 1.3% during
lepirudin treatment and to 0.7% in the posttreatment period. From the start of
lepirudin therapy to the end of follow-up,
lepirudin-treated patients had consistently lower incidences of the combined endpoint than the historical control group (P =.004, log-rank test), primarily because of a reduced risk for new TEC (P =. 005).
Thrombin-
antithrombin levels in the pretreatment period (median, 43.9 microg/L) decreased after the initiation of
lepirudin (at 24 hours +/- 6 hours; median, 9.18 microg/L.) During treatment with
lepirudin, aPTT ratios of 1.5 to 2.5 produced optimal clinical efficacy with a moderate risk for
bleeding, aPTT ratios lower than 1. 5 were subtherapeutic, and aPTT levels greater than 2.5 were associated with high
bleeding risk.
Bleeding events requiring transfusion were significantly more frequent in patients taking
lepirudin than in historical control patients (P =.02). In conclusion, this meta-analysis provides further evidence that
lepirudin is an effective and acceptably safe treatment for patients with HIT.