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Bruce E. Lewis, MD; Diane E. Wallis, MD; Fred Leya, MD; Marcie J. Hursting, PhD; John G. Kelton, MD; for The Argatroban-915 Investigators

Arch Intern Med. 2003;163:1849-1856.

Background  Heparin-induced thrombocytopenia (HIT) is an intensely prothrombotic syndrome managed by discontinuation of heparin therapy and substitution of an alternative inhibitor of thrombin. We describe our experience with argatroban, a direct thrombin inhibitor, in patients with HIT or HIT with thrombosis (HITTS).

Methods  In this multicenter, nonrandomized prospective study, 418 patients with HIT were administered intravenous argatroban, 2 µg/kg per minute, adjusted to maintain the activated partial thromboplastin time at 1.5 to 3 times the baseline value for a mean of 5 to 7 days. Comparisons were made with a historical control cohort (n = 185). The prospectively defined, primary efficacy end point was a composite of all-cause death, all-cause amputation, or new thrombosis in 37 days. Other end points included the components of the composite, death due to thrombosis, increased platelet count, and bleeding.

Results  In the HIT arm, the composite end point was significantly reduced in argatroban-treated patients vs controls (28.0% vs 38.8%; P = .04). In the HITTS arm, the composite end point occurred in 41.5% of argatroban-treated patients vs 56.5% of controls (P = .07). By time-to-event analysis of the composite end point, argatroban therapy was significantly better than historical control therapy in HIT (P = .02) and HITTS (P = .008). Argatroban therapy also significantly reduced new thrombosis in HIT and HITTS and death due to thrombosis in HITTS. There were no significant between-group differences in all-cause death or amputation. Platelet counts recovered more rapidly in argatroban-treated patients than in controls. Bleeding rates were similar between groups.

Conclusion  Argatroban therapy, compared with historical control, improves outcomes, particularly new thrombosis and death due to thrombosis, in patients with heparin-induced thrombocytopenia.

From the Department of Cardiology, Loyola University Medical Center, Maywood, Ill (Drs Lewis and Leya); Midwest Heart Specialists, Downers Grove, Ill (Dr Wallis); Clinical Science Consulting, Potomac, Md (Dr Hursting); and Department of Medicine and Department of Pathology and Molecular Medicine, McMaster University Medical Center, Hamilton, Ontario (Dr Kelton). Dr Lewis has received grants from and been a consultant to Texas Biotechnology Corp (Houston). Dr Wallis has received honorarium from GlaxoSmithKline (Research Triangle Park, NC). Drs Hursting and Kelton are consultants with GlaxoSmithKline.

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