Table 5.

Efficacy endpoints and bleeding complications of direct thrombin inhibitor (DTI) therapy for heparin-induced thrombocytopenia (HIT).

nHIT-Ab Pos, %DTI Treatment Duration (mean days)Treated with Coumarin, %Composite Endpoint† Event-Rate, % (RRR‡)New Thrombosis, Event-Rate, % (RRR‡)Major Bleeding,§ % (Rate per Day of DTI Treatment¦)
Abbreviations: Arg, argatroban; HAT, heparin-associated thrombocytopenia; HIT-Ab Pos, HIT-antibody positive; NA, not available; RRR, relative risk reduction. The data shown have been summarized elsewhere23 and represent a compilation of several studies.17,38,39,44– 46  
* Endpoint assessed from start of lepirudin treatment until end of lepirudin treatment, i.e., a shorter observation period than the remaining lepirudin and argatroban studies (which included a posttreatment observation period until day 35 or day 37, respectively). 
†Composite endpoint defined as all-cause mortality, limb amputation, or new thrombosis (each patient could contribute only 1 event). 
‡RRR (relative risk reduction) values shown were determined from the categorical analysis; using hazard ratios (reported in the argatroban studies), somewhat greater RRR values were observed (not shown). 
§Major bleeding was defined as bleeding requiring transfusion (lepirudin meta-analysis), as major bleeding likely caused by lepirudin (lepirudin postmarketing study), or as overt bleeding associated with hemoglobin fall > 2 g/L that led to transfusion of > 2 units of blood or bleeding that was intracranial, retroperitoneal, or into a prosthetic joint (argatroban studies). 
¦Indicates major bleeding rate divided by mean duration of DTI therapy reported in the trial. 
¶Value may overestimate composite endpoint (not reported), as 15.7% is the sum of the individual efficacy endpoints. 
#The relatively low bleeding rate could reflect reduced reporting in this (retrospective) postmarketing study and inclusion of only those patients in whom bleeding was judged to have been caused by lepirudin. 
**In the Arg-911 and Arg-915 trials, 62% and 63% of patients received warfarin, respectively, but the breakdown between patients with isolated HIT and HIT complicated by thrombosis was not given. 
††Positive testing for HIT antibodies was required for study entry. 
Isolated HIT 
Lepirudin studies 
    Meta-analysis44  111 100 13.5 NA 9.0* (—) 2.7* (—) 14.4 * (1.1) 
    Postmarketing45  612 66 11.1 NA 15.7*¶ (—) 2.1* (—) 5.9*# (0.5) 
Argatroban studies 
    Arg-91138  160 50 5.3 62** 25.6 (0.34) 8.1 (0.65) 3.1 (0.6) 
    Arg-91539  189 NA 5.1 63** 28.0 (0.28) 5.8 (0.75) 5.3 (1.0) 
HIT complicated by thrombosis 
Lepirudin studies 
    HAT-1,217  113 100†† 13.3 ≥83 21.3 (0.55) 10.1 (0.63) 18.8 (1.4) 
    HAT-346  98 100†† 14 NA 21.5 (0.55) 6.1 (0.78) 20.4 (1.5) 
    Postmarketing45  496 77 12.1 NA 22.0* (0.54) 5.2* (0.81) 5.4*# (0.4) 
Argatroban studies 
    Arg-91138  144 65 5.9 62** 43.8 (0.22) 19.4 (0.44) 11.1 (1.9) 
    Arg-91539  229 NA 7.1 63** 41.5 (0.27) 13.1 (0.62) 6.1 (0.9) 
nHIT-Ab Pos, %DTI Treatment Duration (mean days)Treated with Coumarin, %Composite Endpoint† Event-Rate, % (RRR‡)New Thrombosis, Event-Rate, % (RRR‡)Major Bleeding,§ % (Rate per Day of DTI Treatment¦)
Abbreviations: Arg, argatroban; HAT, heparin-associated thrombocytopenia; HIT-Ab Pos, HIT-antibody positive; NA, not available; RRR, relative risk reduction. The data shown have been summarized elsewhere23 and represent a compilation of several studies.17,38,39,44– 46  
* Endpoint assessed from start of lepirudin treatment until end of lepirudin treatment, i.e., a shorter observation period than the remaining lepirudin and argatroban studies (which included a posttreatment observation period until day 35 or day 37, respectively). 
†Composite endpoint defined as all-cause mortality, limb amputation, or new thrombosis (each patient could contribute only 1 event). 
‡RRR (relative risk reduction) values shown were determined from the categorical analysis; using hazard ratios (reported in the argatroban studies), somewhat greater RRR values were observed (not shown). 
§Major bleeding was defined as bleeding requiring transfusion (lepirudin meta-analysis), as major bleeding likely caused by lepirudin (lepirudin postmarketing study), or as overt bleeding associated with hemoglobin fall > 2 g/L that led to transfusion of > 2 units of blood or bleeding that was intracranial, retroperitoneal, or into a prosthetic joint (argatroban studies). 
¦Indicates major bleeding rate divided by mean duration of DTI therapy reported in the trial. 
¶Value may overestimate composite endpoint (not reported), as 15.7% is the sum of the individual efficacy endpoints. 
#The relatively low bleeding rate could reflect reduced reporting in this (retrospective) postmarketing study and inclusion of only those patients in whom bleeding was judged to have been caused by lepirudin. 
**In the Arg-911 and Arg-915 trials, 62% and 63% of patients received warfarin, respectively, but the breakdown between patients with isolated HIT and HIT complicated by thrombosis was not given. 
††Positive testing for HIT antibodies was required for study entry. 
Isolated HIT 
Lepirudin studies 
    Meta-analysis44  111 100 13.5 NA 9.0* (—) 2.7* (—) 14.4 * (1.1) 
    Postmarketing45  612 66 11.1 NA 15.7*¶ (—) 2.1* (—) 5.9*# (0.5) 
Argatroban studies 
    Arg-91138  160 50 5.3 62** 25.6 (0.34) 8.1 (0.65) 3.1 (0.6) 
    Arg-91539  189 NA 5.1 63** 28.0 (0.28) 5.8 (0.75) 5.3 (1.0) 
HIT complicated by thrombosis 
Lepirudin studies 
    HAT-1,217  113 100†† 13.3 ≥83 21.3 (0.55) 10.1 (0.63) 18.8 (1.4) 
    HAT-346  98 100†† 14 NA 21.5 (0.55) 6.1 (0.78) 20.4 (1.5) 
    Postmarketing45  496 77 12.1 NA 22.0* (0.54) 5.2* (0.81) 5.4*# (0.4) 
Argatroban studies 
    Arg-91138  144 65 5.9 62** 43.8 (0.22) 19.4 (0.44) 11.1 (1.9) 
    Arg-91539  229 NA 7.1 63** 41.5 (0.27) 13.1 (0.62) 6.1 (0.9) 
View Large
This Feature Is Available To Subscribers Only

or Create an Account

Close Modal
Close Modal