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Harvey D. White on behalf of the ACUITY investigators

Safety and Efficacy of Switching from Either UFH or Enoxaparin Plus a GP IIb/IIIa Inhibitor to Bivalirudin Monotherapy in Patients with Non-ST Elevation ACS Managed with an Invasive Strategy: Results from the Randomized ACUITY Trial. Harvey D. White on behalf of the ACUITY investigators.

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Harvey D. White on behalf of the ACUITY investigators

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  1. Safety and Efficacy of Switching from Either UFH or Enoxaparin Plus a GP IIb/IIIa Inhibitor to Bivalirudin Monotherapy in Patients with Non-ST Elevation ACS Managed with an Invasive Strategy: Results from the Randomized ACUITY Trial Harvey D. White on behalf of the ACUITY investigators

  2. Disclosures • Research Grants: • Alexion, Fournier Laboratories, Sanofi Aventis, Johnson & Johnson, Eli Lilly, Proctor & Gamble, Merck Sharpe & Dohme, Schering Plough, Roche, The Medicines Company, Glaxo Smith Kline, Pfizer, Neuren Pharmaceuticals, NIH • Consultant: • Sanofi Aventis, The Medicines Company

  3. Medical management UFH or Enoxaparin + GP IIb/IIIa PCI Bivalirudin + GP IIb/IIIa Angiography within 72h R* Bivalirudin Alone CABG ACUITY Study Design Moderate-high risk unstable angina or NSTEMI undergoing an invasive strategy (N = 13,819) Moderate- high risk ACS Aspirin in all Clopidogrel dosing and timing per local practice *Stratified by pre-angiography thienopyridine use or administration ACUITY Design. Stone GW et al. AHJ 2004;148:764–75

  4. Primary Endpoints • Net Clinical Outcomes • Death, MI, unplanned revascularization for ischemia or non-CABG major bleeding • Composite Ischemia • Death, MI or unplanned revascularization for ischemia • Major Bleeding (Non-CABG) • Intracranial, intraocular, or retroperitoneal bleeding • Access site bleed requiring intervention/surgery • Hematoma ≥5 cm • Hgb ≥4g/dL w/o overt source • Hgb ≥3g/dL with an overt source • Reoperation for bleeding • Any blood transfusion ACUITY Design. Stone GW et al. AHJ 2004;148:764–75

  5. UFH/Enox + GP IIb/IIIa vs. Bivalirudin + GP IIb/IIIa vs. Bivalirudin Alone PNI <0.001 PSup = 0.015 PNI = 0.01 PSup = 0.32 PNI <0.001 PSup <0.001 ACUITY: Primary results – 30 days Stone GW et al. NEJM 2006;355:2203-16

  6. Ischemic Composite Endpoint(Death, MI, unplanned revascularization for ischemia) 30 day P (log rank) 1 year P (log rank) Estimate Estimate p=0.55 UFH/Enoxaparin + IIb/IIIa 7.4% — 16.3% — 0.36 0.38 Bivalirudin + IIb/IIIa 7.8% 16.5% 0.34 0.31 Bivalirudin alone 7.9% 16.4% UFH/Enoxaparin + GPI vs. Bivalirudin + GPI vs. Bivalirudin Alone 25 20 15 Ischemic Composite (%) 10 Bivalirudin+GPI vs. Hep+GPI HR [95% CI] = 1.05 (0.94-1.16) 5 Bivalirudin alone vs. Hep+GPI HR [95% CI] = 1.05 (0.95-1.17) 0 0 30 60 90 120 150 180 210 240 270 300 330 360 390 Days from Randomization Stone GW. ACC 2007 presentation

  7. Mortality: 524 total deaths at 1-year p=0.90 UFH/Enoxaparin + IIb/IIIa Bivalirudin + IIb/IIIa Bivalirudin alone P (log rank) 1 year P (log rank) Estimate Estimate 1.4% — 4.4% — 0.53 0.93 1.6% 4.2% 0.39 0.66 1.6% 3.8% UFH/Enoxaparin + GPI vs. Bivalirudin + GPI vs. Bivalirudin Alone 5 Bivalirudin+GPI vs. Hep+GPI HR [95% CI] = 0.99 (0.80-1.22) 4 Bivalirudin alone vs. Hep+GPI HR [95% CI] = 0.95 (0.77-1.18) 3 Mortality (%) 2 30 day 1 0 0 30 60 90 120 150 180 210 240 270 300 330 360 390 Days from Randomization Stone GW. ACC 2007 presentation

  8. Background and Objectives of the Current Analysis • Background • In prior studies, post-randomization crossover from UFH to enoxaparin or vice versa was associated with increased adverse events • In ACUITY, switching at randomization from prior UFH/enoxaparin to bivalirudin monotherapy was associated with significantly improved bleeding while preserving a similar rate of ischemia • Objective • Evaluate the effects of switching from pre-randomization UFH/Enox + GPI to bivalirudin monotherapy at randomization on 30-day and 1-year outcomes

  9. ACUITY Overall: Switch from Prior Antithrombin 30 day Results 1 year Results Risk Ratio±95% CI Hazard Ratio±95% CI RR (95% CI) HR (95% CI) Switch to Bivalirudin better Switch to Bivalirudin better Consistent UFH/Enox + IIb/IIIa better Consistent UFH/Enox + IIb/IIIa better

  10. ACUITY PCI: Switch from Prior Antithrombin 30 day Results 1 year Results Risk Ratio±95% CI Hazard Ratio±95% CI RR (95% CI) HR (95% CI) Switch to Bivalirudin better Switch to Bivalirudin better Consistent UFH/Enox + IIb/IIIa better Consistent UFH/Enox + IIb/IIIa better * High risk = ↑Tn, CKMB or ECG Δ’s White HD, ESC 2007.

  11. Study Population – Current Analysis Received UFH/Enox + GPI prior to Randomization N=371 Randomized to bivalirudin monotherapy (switched therapy) N=164 Randomized to UFH/Enox + GPI (consistent therapy) N=207

  12. Baseline Characteristics

  13. Baseline Characteristics *Prior to angiography or PCI

  14. 30-Day Outcomes 30 Day Events (%)

  15. 30-Day Composite Ischemia Outcomes 30 Day Events (%)

  16. 1-Year Outcomes

  17. Study Limitations • Small, post-hoc analysis

  18. Conclusions • In a small post-hoc analysis, switching from UFH/enoxaparin + a GP IIb/IIIa inhibitor to bivalirudin monotherapy was safe and effective, with an approximate 50% reduction in major bleeding and comparable ischemic events • Results of this analysis are consistent with overall ACUITY findings

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