Heparin-induced thrombocytopenia with thromboembolic complications: meta-analysis of 2 prospective trials to assess the value of parenteral treatmentwith lepirudin and its therapeutic aPTT range

This mete-analysis focuses on 2 prospective studies in patients with hepari n-induced thrombocytopenia (HIT) and thromboembolic complication (TEC) who were treated with lepirudin (n = 113), Data were compared with those of a h istorical control group (n = 91), The primary endpoint (combined incidence of death, new TEC, and limb amputation) occurred in 25 lepirudin-treated pa tients (22.1%; 95% CI, 14.5%-29.8%): 11 died (9.7%; 95% Cl, 4.9%-16.8%), 7 underwent limb amputation (6.2%; 95% CI, 2.5%-12.3%), and 12 experienced ne w TEC (10.6%; 95% CI, 5.8%-18.3%), The risk was highest in the period betwe en 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 trea tment and to 0.7% in the posttreatment period. From the start of lepirudin therapy to the end of follow-up, lepirudin-treated patients had consistentl y lower incidences of the combined endpoint than the historical control gro up (P = .004, log-rank test), primarily because of a reduced risk for new T EC (P = .005), Thrombin-antithrombin levels in the pretreatment period (med ian, 43.9 mu g/L) decreased after the initiation of lepirudin (at 24 hours +/- 6 hours; median, 9.18 mu g/L.) During treatment with lepirudin, aPTT ra tios 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 leve ls greater than 2.5 were associated with high bleeding risk. Bleeding event s requiring transfusion were significantly more frequent in patients taking lepirudin than in historical control patients (P = .02), In conclusion, th is mete-analysis provides further evidence that lepirudin is an effective a nd acceptably safe treatment for patients with HIT. (C) 2000 by The America n Society of Hematology.