Hero1 Hero2

Multicenter, open-label study (Topol et al., 1993)

Hirulog (Bivalirudin) Angioplasty study (Bittl, 1995; Bittl etal., 1995)

Bivalirudin Angioplasty Trial (Bittl et al., 2001)a

Comparison of Abciximab Complications with Hirulog Ischemic

Events Trial (Lincoff et al., 2002b) Randomized Evaluation in PCI Linking Angiomax to Reduced

Clinical Events (REPLACE)-1 Trial (Lincoff et al., 2002a) Randomized Evaluation in PCI Linking Angiomax to Reduced

Clinical Events (REPLACE)-2 Trial (Lincoff et al., 2003) Cho et al. (2003)

Acute Catheterization and Urgent intervention Triage Strategy

Trial (Stone et al., 2004, 2006) Thrombin inhibition in Myocardial ischemia-7 (Fuchs and

Cannon, 1995) Thrombolysis in inhibition in Myocardial ischemia-8

(Antman et al., 2002) Hirulog Early Reperfusion/Occlusion-1 (White etal., 1997) Hirulog Early Reperfusion/Occlusion-2 (White, 2001)

aBittl et al. (1995) reported the first study (combining two randomized, controlled trials) comparing bivalirudin against heparin for PCI; this study, subsequently called the Bivalirudin Angioplasty Trial (BAT), was later reanalyzed (including data from an additional 214 patients) (Bittl et al., 2001).

bApproximately 56% of patients in ACUITY underwent PCI, about 11% were triaged to CABG, and the rest were medically managed.

Abbreviations: ACS, acute coronary syndromes; PCI, percutaneous coronary intervention.

in patients who underwent angioplasty for unstable angina and included fewer episodes of major hemorrhage, retroperitoneal bleeding, and need for blood transfusion (Topol et al., 1993; Bittl et al., 1995, 2001; Campbell et al., 2000a; Antman and Braunwald, 2001).

CACHET (phases A, B, and C) evaluated the combination of bivalirudin plus the provisional use of a GPIIb/IIIa inhibitor (abciximab) in comparison to heparin and abciximab in patients undergoing balloon angioplasty and stenting. Bivalirudin was found to be safe and effective with stents and was associated with a lower combined incidence of death, MI, revascularization, or major hemorrhage at 7 days (Nawarskas and Anderson, 2001; Lincoff et al., 2002b; Sciulli and Mauro, 2002).

In the REPLACE-1 trial, heparin was compared to bivalirudin in patients undergoing coronary stenting with any one of the GPIIb/IIIa inhibitors (at the discretion of the physician) in 1056 patients. The combined endpoint of death, MI, or revascularization showed a trend toward a reduction in bivalirudin-treated patients at 48 h (Lincoff et al., 2002a).

The REPLACE-2 trial was a randomized, double-blind, active-controlled trial of 6010 patients who received bivalirudin with provisional use of GPIIb/IIIa blockage or heparin with planned GPIlb/IIIa inhibition. Bivalirudin was found to be superior to heparin alone and as effective as heparin plus GPIlb/IIIa inhibition for ischemic protection (Lincoff et al., 2003). A significant reduction in the incidence of bleeding and thrombocytopenia were also noted.

Bivalirudin may be a suitable substitute for heparin in patients with chronic renal disease who require PCI because its clearance is primarily determined by proteolysis and not by renal excretion (Robson et al., 2002). ACT monitoring is recommended in patients with chronic renal disease. The dose of bivalirudin may need to be reduced in accordance with the degree of renal impairment, as discussed earlier. If the creatinine clearance is 30 mL/min or less, reduction of the infusion rate to 1.0mg/kg/h should be considered, while if the patient is on hemodialysis, the infusion should be reduced to 0.25mg/kg/h (Robson, 2000; Robson et al., 2002; The Medicines Company, 2005) (Table 1).

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