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FIGURE 3 Efficacy outcomes: comparison of danaparoid (with or without coumarin) with ancrod (with or without coumarin) or coumarin alone. Time-to-event analysis of composite endpoint (new thrombosis, thrombotic death, amputation; maximum, one event per patient). The primary efficacy endpoint (at day 7) was reduced in the danaparoid-treated patients (p = 0.001, log-rank test); at day 35 (secondary endpoint), the composite endpoint remained reduced (p = 0.0022, log-rank test). When a different composite endpoint that included all-cause mortality was analyzed (i.e., new thrombosis, all-cause mortality, amputation; maximum, one event per patient), the differences remained significant (day 35; p = 0.0013 by log-rank test; data not shown). Source: From Lubenow et al., 2006.

Days

FIGURE 3 Efficacy outcomes: comparison of danaparoid (with or without coumarin) with ancrod (with or without coumarin) or coumarin alone. Time-to-event analysis of composite endpoint (new thrombosis, thrombotic death, amputation; maximum, one event per patient). The primary efficacy endpoint (at day 7) was reduced in the danaparoid-treated patients (p = 0.001, log-rank test); at day 35 (secondary endpoint), the composite endpoint remained reduced (p = 0.0022, log-rank test). When a different composite endpoint that included all-cause mortality was analyzed (i.e., new thrombosis, all-cause mortality, amputation; maximum, one event per patient), the differences remained significant (day 35; p = 0.0013 by log-rank test; data not shown). Source: From Lubenow et al., 2006.

Finally, a review of 1478 danaparoid-treated patients available from the company files (including the compassionate-use program and spontaneous adverse event reports) and independent published literature has been made (Magnani and Gallus 2006). A wide variety of clinical uses were described, ranging from treatment of thromboembolism to extracorporeal support for renal failure, from routine medical use to major general and cardiovascular surgery, and including elderly and pediatric patients, and pregnancy. In all these settings, danaparoid appeared to be safe and effective in treating HIT and associated

TABLE 2 Comparison of Efficacy and Major Bleeding Endpoints of Danaparoid, Lepirudin, and Argatroban vs. Control

Composite efficacy3 Major bleeding3

Study Drug studied Study drug Control Study drug Control

Lubenow etal., 2006 Danaparoid 24.2%b 50.0% 12.9%b 33.9%

aUp to day 35 for danaparoid and lepirudin: day 37 for argatroban. bStatistically significant (p < 0.01) compared with control (by categorical analysis). Abbreviation: HAT, heparin-associated thrombocytopenia. Source: From Lubenow et al., 2006.

thromboses. The frequency of a composite of adverse outcomes (new/extended thrombosis, new/persistent platelet count reduction, unplanned amputation) during the treatment period (range, 1 day to 3.5 yr), plus a follow-up period (up to 3 mo), was 16.4%. Thrombotic events occurred in 11.0% of the patients, whereas major bleeding was reported in 8.1%.

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