The treatment for heparin-induced thrombocytopenia (HIT) has undergone important changes over the past decade. Until recently, clinicians had very few options for treating this potentially devastating syndrome. Fortunately, with the development of several contemporary anticoagulants, physicians now have a number of novel treatment options. These include danaparoid, an indirect (antithrombin-dependent) factor Xa inhibitor (see Chapter 13) and the direct thrombin inhibitors (DTIs), including recombinant hirudin (r-hirudin) (e.g., lepirudin) (see Chapter 14) and the small molecule DTI, argatroban (Alving, 2003; Chong, 2003; Warkentin, 2003) (see Chapter 15). The synthetic pentasaccharide (fondaparinux), another indirect factor Xa inhibitor, has also been used "off-label" to treat HIT (Spinler, 2006).

More recently, another DTI, bivalirudin (Angiomax), has been approved in the United States for use in HIT, but only for those patients undergoing percutaneous transluminal coronary angioplasty (PTCA). Bivalirudin is also approved in the United States, Canada, New Zealand, Israel, Argentina, and the 25 members of the EU for use as an anticoagulant in patients undergoing PTCA. In the EU it is marketed under the trade name Angiox™ (Warkentin and Koster, 2005). It too has been used "off-label" for HIT, especially in interventional settings (e.g., cardiac surgery) and in patients with combined renal and hepatic dysfunction.

Bivalirudin is a hirulog, i.e., one of a group of drugs designed from the structure of hirudin (analogue of hirudin). It was developed in the early 1990s by the Biogen Corporation (Cambridge, MA, USA), and was originally known as BG8967 or Hirulog. The U.S. Food and Drug Administration (FDA) mandated a name change to avoid confusion with Humalog (recombinant human insulin) when The Medicines Company (Parsippany, NJ, USA) acquired licensure for bivalirudin in 1997. The name was then changed to Angiomax. Currently, the major indications for bivalirudin are for use in patients with unstable angina undergoing PTCA and also with provisional glycoprotein (GP) IIb/IIIa receptor inhibitor treatment to reduce acute ischemic events in select patients undergoing percutaneous coronary intervention (PCI).

Bivalirudin has also been used with favorable results in both "on-pump" and "off-pump" cardiac surgery cases in patients with and without HIT. A clinical trial completed by Merry and colleagues (2004) in New Zealand compared bivalirudin with unfractionated heparin (UFH) (with protamine reversal) in non-HIT patients requiring off-pump coronary artery bypass (OPCAB) surgery. Favorable results, including improved graft patency and comparable hemorrhage and transfusion requirements, led to two subsequent multicenter trials. The CABG

HIT/TS On- and Off-Pump Safety and Efficacy (CHOOSE-ON and CHOOSE-OFF studies for patients with HIT, and the Evaluation of Patients during coronary artery bypass graft Operations: Linking UTilization of bivalirudin to Improved Outcomes and New anticoagulation strategies (EVOLUTION-OFF and EVOLU-TION-ON) trials, were conducted to evaluate the safety and efficacy of bivalirudin as an alternative to UFH (and protamine reversal) in the HIT and non-HIT settings, respectively. To date, results of these studies (Dyke et al., 2006, 2007; Smedira et al., 2006; Koster et al., 2007) have revealed comparable safety and efficacy endpoints.

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