J Am Coll Cardiol 2008;51:1734–41 Safety and Efficacy of Switching From Either Unfractionated Heparin or Enoxaparin to Bivalirudin in Patients With Non–ST-Segment Elevation Acute Coronary Syndromes Managed With an Invasive Strategy Harvey D. White, Derek P. Chew, James W. Hoekstra, Chadwick D. Miller, Charles V. Pollack, JR, Frederick Feit, A. Michael Lincoff, Michel Bertrand, Stuart Pocock, James Ware, E. Magnus Ohman, Roxana Mehran, Gregg W. Stone Auckland, New Zealand; Adelaide, Australia; Winston-Salem and Durham, North Carolina; Philadelphia, Pennsylvania; New York, New York; Cleveland, Ohio; Lille, France; London, United Kingdom; and Boston, Massachusetts Results From the ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) Trial

Introduction SYNERGY trial –Crossed over after randomization from UFH to ENOX or vice versa -> had increased rates of death/MI JAMA. 2005;294: N Engl J Med 2006;354:

REPLACE-2 randomized trial. JAMA. 2003;289: ACUTY trial N Engl J Med. 2006;355:

Object determine whether patients could be safely switched from UFH or ENOX to bivalirudin.

Materials and Methods Entry criteria –patients ≥ 18 years of age with symptoms of unstable angina lasting 10 min within the preceding 24 h were eligible for enrollment –new ST-segment depression or transient elevation ≥ 1 mm –troponin I, troponin T, or creatine kinase-MB elevation –known coronary artery disease –4 other Thrombolysis In Myocardial Infarction unstable angina risk criteria positive Exclusion criteria –acute ST-segment elevation MI or shock –bleeding diathesis or major bleed within 2 weeks –thrombocytopenia –calculated creatinine clearance < 30 ml/min.

Figure 1 Flow of ACUITY Trial and Patients Switched

Table 1 Baseline Characteristics

Table 2 Clinical Outcomes at 30Days

Table 1 Baseline Characteristics

Table 2 Clinical Outcomes at 30Days

Figure 2 Outcomes of Patients Switched

Table 3 Clinical Outcomes at 30 Days According to Consistent Therapy on UFH Versus Switch From UFH to Bivalirudin

Table 4 Clinical Outcomes at 30 Days According to Consistent Therapy on Enoxaparin Versus Switch From Enoxaparin to Bivalirudin

Discussion

direct thrombin inhibitor with a short half-life (25 minutes) ->enabling “fast-on, fast-off” activity inhibits thrombin-mediated platelet activation - not promote platelet activation and aggregation predictable dose response -no continuous ACT monitoring is required Discussion

Conclusions In patients with moderate- and high-risk NSTE-ACS –switching from either UFH or ENOX to bivalirudin monotherapy before angiography ; similar rate of composite ischemia compared with consistent treatment with UFH or ENOX plus a GP IIb/IIIa inhibitor ; 50% reduction in major bleeding - bivalirudin monotherapy ; Significant reduction in major bleeding Similar rates of composite ischemia