1 / 23

Presenter Disclosure Information

Safety and Efficacy of Bivalirudin in Patients with Non-ST Elevation Acute Coronary Syndromes Undergoing Medical Management: One Year Results from the Randomized ACUITY Trial.

cairo-richmond
Download Presentation

Presenter Disclosure Information

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Safety and Efficacy of Bivalirudin in Patients with Non-ST Elevation Acute Coronary Syndromes Undergoing Medical Management: One Year Results from the Randomized ACUITY Trial Walter Desmet, Lars Rasmussen, A. Michael Lincoff, Angel Cequier, Hans-Jürgen Rupprecht, Bernard Gersh, Steven Manoukian, Michel Bertrand, Gregg Stone

  2. Presenter Disclosure Information Walter Desmet, MD, PhD Safety and Efficacy of Bivalirudin in Patients With Non-ST Elevation Acute Coronary Syndromes Undergoing Medical Management:One Year Results from the Randomized ACUITY Trial FINANCIAL DISCLOSURE: no disclosure to make UNLABELED/UNAPPROVED USES DISCLOSURE: Bivalirudin is not approved for the indication discussed

  3. Background: Current Management of ACS • Early invasive strategy if moderate-high risk1,2 • Median time to cath 21 hours3 • Revascularization with PCI or CABG1,2 • 55% PCI, 12% CABG, 33% medical mgt3 • Triple anti-platelet therapy1,2 • Aspirin • Clopidogrel (initiated pre or post angiography) • GP IIb/IIIa inhibitors • - started upstream in all pts or in the CCL for PCI • Unfractionated or LMW heparin1,2,4 1 Braunwald et al JACC 2002; 2 Bassand et al. EHJ 2007; 3www.crusade.org; 4SYNERGY. JAMA 2004;292:45-54

  4. Advantages of the direct thrombin inhibitor bivalirudin No requirement for anti-thrombin III Effective on clot-bound thrombin Inhibits thrombin-mediated platelet activation No interactions with PF- 4 Plasma half-life 25 minutes No requirement for anticoagulant monitoring Clinical results with bivalirudin in PCI Similar protection from ischemic events as UFH +GP IIb/IIIa inhibitors, with markedly reduced bleeding1 Not previously tested in contemporary ACS patients Bivalirudin as an Alternative to UFH/LMWH REPLACE 2. Lincoff AM et al. JAMA 2003;289:853-863

  5. 89 (0.6%) Norway Sweden 175 (1.3%) 150 (1.1%) Denmark Finland 51 (0.4%) 132 (1.0%) Netherlands 438 (3.2%) Canada 198 (1.4%) Belgium Poland 14 (0.1%) 162 (1.2%) UK Germany 2561 (18.5%) 155 (1.1%) France 7851 (56.8%) USA Austria 356 (2.6%) Italy 238 (1.7%) 547 (4.0%) Spain 203 (1.5%) New Zealand 499 (3.6%)Australia ACUITY Enrollment 13,819 pts randomized at 448 centers in 17 countries

  6. Medical management UFH or Enoxaparin + GP IIb/IIIa PCI Bivalirudin + GP IIb/IIIa Angiography within 72h R* Bivalirudin Alone CABG Study Design – Primary Randomization 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

  7. Major Entry Criteria Moderate-high risk unstable angina or NSTEMI Inclusion Criteria Exclusion Criteria • Age ≥18 years • Chest pain ≥10’ within 24h • At least one of: • New ST depression or transient ST elevation ≥1 mm • Troponin I, T, or CKMB • Documented CAD • All other 4 TIMI risk criteria • Age ≥65 years • Aspirin within 7 days • ≥2 angina episodes w/i 24h • ≥3 cardiac risk factors • Written informed consent • No angiography within 72h • Acute STEMI or shock • Bleeding diathesis or major bleed within 2 weeks • Platelet count ≤100,000/mm3 • INR >1.5 control • CrCl ≤30 ml/min • Abcx or ≥2 prior LMWH doses • Prior UFH, LMWH (1 dose), eptifibatide and tirofiban were allowed • Allergy to drugs, contrast ACUITY Design. Stone GW et al. AHJ 2004;148:764–75

  8. Primary Endpoints (at 30 days) Net Clinical Outcome (Composite Ischemia, Non-CABG Major Bleeding) Composite Ischemia: • Death from any cause • Myocardial infarction • During medical Rx: Any biomarker elevation >ULN • Post PCI: CKMB >ULN with new Q waves or >3x ULN w/o Q waves • Post CABG: CKMB >5x ULN with new Q waves, >10x ULN w/o Q waves • Unplanned revascularization for ischemia Non CABG related bleeding • Intracranial bleeding or intraocular bleeding • Retroperitoneal bleeding • Access site bleed requiring intervention/surgery • Hematoma ≥5 cm • Hgb  ≥ 3 g/dL with , or  ≥ 4 g/dL without overt source • Blood product transfusion • Reoperation for bleeding

  9. Primary Endpoints (at 1 Year) Composite Ischemia: • Death from any cause • Myocardial infarction • During medical Rx: Any biomarker elevation >ULN • Post PCI: CKMB >ULN with new Q waves or >3x ULN w/o Q waves • Post CABG: CKMB >5x ULN with new Q waves, >10x ULN w/o Q waves • Unplanned revascularization for ischemia

  10. Invasive Management *in patients receiving study antithrombin pre angiography †median (IQR)

  11. Overall 30-day Results by Treatment Arm †non-inferiority; ‡superiority Stone GW et al. NEJM 2006;355:2203-16

  12. 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% 1 Year Composite Ischemia by Treatment Arm Overall Population 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

  13. 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% 1 Year Mortality by Treatment Arm Overall Population 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

  14. Heparin + IIb/IIIa N = 1,493 Bivalirudin + IIb/IIIa N = 1,496 Bivalirudin alone N = 1,502 Management Strategy (N=13,819) CABG (n=1,539) PCI (n=7,789) 56.4% 11.1% 32.5% MM (n=4,491)

  15. MM 32.5 % PCI 56.4 % Angiography within 72h R* CABG 11.1% Purpose of this post-hoc analysis Compare clinical outcome of patients managed medically 1) to clinical outcome in revascularized patients 2) between the 3 randomization groups *Stratified by pre-angiography thienopyridine use or administration ACUITY Design. Stone GW et al. AHJ 2004;148:764–75

  16. Patient Characteristics

  17. Medical Management (MM) Non-Medical Management (non-MM) 16 12 8 4 0 Net Clinical Outcome Composite Ischemia Major Bleeding 30-day Results by Management Strategy P<0.001 14.0% P<0.001 9.9% 30 day events (%) P<0.001 5.5% 5.5% 3.1% 2.9%

  18. Heparin + GP IIb/IIIa (N = 1,493) Bivalirudin + GPI (N = 1,496) 10 P=0.06 P=0.09 Bivalirudin (N = 1,502) 8 P=0.67 P=0.36 P<0.001 P=0.004 6 4 2 0 Net Clinical Outcome Composite Ischemia Major Bleeding 30 Day Results by Treatment Arm Medical Management Population 6.5% 30 day events (%) 5.1% 4.9% 4.4% 3.4% 3.1% 2.8% 2.5% 1.9%

  19. Medical Management (MM) (N = 4,491) Non-Medical Management (non-MM) (N = 9,328) 20 16 12 8 4 0 Composite Ischemia Mortality 1 Year Results by Management Strategy P<0.0001 19.0% Percentage (%) 8.9% P=0.65 3.9% 3.7%

  20. P=0.99 P=0.81 Heparin + GP IIb/IIIa (N = 1,493) Bivalirudin + GPI (N = 1,496) Bivalirudin (N = 1,502) 1 Year Results by Treatment Arm Medical Management Population 10 9.0% 9.0% 8.7% P=0.84 P=0.75 8 Percentage (%) 6 4.0% 3.9% 3.8% 4 2 0 Ischemic Composite Mortality

  21. Influence of Major Bleeding and MI in the First 30 Days on Risk of Death Over 1 Year Medical Management Population HR (95% CI) P-value HR ± 95% CI Cox model adjusted for baseline predictors, with non-CABG major bleeding and MI as time-updated covariates

  22. Comprise a unique patient cohort with different demographic risk factors fewer high-risk features (trop  / ECG ∆) less major bleeding fewer ischemic events than patients requiring PCI or CABG Conclusions Patients triaged to medical management with moderate and high risk NSTE-ACS

  23. Conclusions In moderate and high risk NSTE-ACS patients triaged to medical management • Bivalirudin with or without a GPI results in marked reduction of bleeding at 30 days, while preserving the ischemic and mortality benefit at 1-year • Early iatrogenic bleeding complications are significantly associated with long-term prognosis

More Related