Alternative Anticoagulants Are Expensive and Do Not Improve Outcomes with HIT

The only randomized controlled trial of HIT therapies (danaparoid versus dextran-70) experienced very slow patient recruitment, probably because of the widely perceived (and ultimately demonstrable) superiority of danaparoid (Chong et al., 2001) (see Chapter 13). In the pivotal studies of the direct thrombin inhibitors, lepirudin and argatroban, it was deemed unethical to have placebo controls, and so historical controls were used (see Chapters 14 and 15). Nevertheless, clear benefit has been demonstrated consistently, not only for the designated primary composite endpoints (all-cause mortality, limb amputation, new thromboemboli) but particularly for the endpoint in which an effective antithrombotic agent would be expected to show the most impact, namely new thromboemboli (Lewis et al., 2006). (This is because most deaths in HIT patient series are due to non-thrombotic events, such as multi-organ failure, cancer, and other non-HIT co-morbidities, and amputations are often performed on limbs already doomed by the time of initiation of alternative anticoagulation, and perhaps too because these prospective cohort studies were done before warfarin's adverse effect profile was appreciated.) There is no question of efficacy of alternative anticoagulants among those with experience managing HIT, who have often witnessed dramatic reversals of the thrombotic "storm" with therapy.

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