Successfully reported this slideshow.
We use your LinkedIn profile and activity data to personalize ads and to show you more relevant ads. You can change your ad preferences anytime.

Montalescot G - Bivalirudin in high risk PCI and ACS

913 views

Published on

Is Bivalirudin the ideal anticoagulant therapy in high risk PCI and following ACS?

  • Be the first to comment

Montalescot G - Bivalirudin in high risk PCI and ACS

  1. 1. Controversies in antithrombotic therapy Bivalirudin is the ideal anticoagulant therapy in high risk PCI and following ACS G. Montalescot www.action-coeur.org COI DISCLOSURE FOR DR. MONTALESCOT: Gilles Montalescot reports: research grants to the institution or consulting/lecture fees from Abbott Vascular, Accumetrics, AstraZeneca, Bayer, Biotronik, BMS, Boehringer-Ingelheim, Daiichi-Sankyo, Duke Institute, Eli Lilly and Company, Europa, Fédération Française de Cardiologie, Fondation de France, GSK, INSERM, Institut de France, Iroko, Lead-up, Menarini, Medtronic, Nanospheres, Novartis, Pfizer, Roche, Sanofi-Aventis, Stentys, Société Française de Cardiologie, Springer, The Medicines Company, The TIMI group, WebMD, and Wolters.
  2. 2. Bivalirudin is the ideal anticoagulant therapy in high risk PCI and following ACS
  3. 3. Is bivalirudin more effective than UFH and IIb/IIIa inh. In REPLACE-2? Secondary EP 10 Death, MI, Urg Rev (%) Odds Ratio = 1.088 (0.895 - 1.322) 8 6 p = 0.40 7.1 7.6 Primary EP Death, MI, URev, Maj Bld (%) 12 10 Odds Ratio = 0.917 (0.772 - 1.089) 10.0 p = 0.32 9.2 8 6 4 4 2 0 2 Heparin+ GP IIb/IIIa (n=3008) Bivalirudin (n=2994) 0 Heparin+ GP IIb/IIIa (n=3008) Bivalirudin (n=2994) Lincoff AM et al. JAMA 2003
  4. 4. Is bivalirudin safer than UFH and IIb/IIIa inh. In REPLACE-2? UFH + GP IIb/IIIa Bivalirudin Heparin protocol: p <0.001 •If ACT < 225 seconds, additional 20 U/kg administered 4.1 2.4 • NET RESULT = Median ACT 320s with UFH+GP IIb-IIIa RA Major much higher than: - recommended by Guidelines - recommended in PDR of GP IIb/IIIa RA - recommended in modern GP IIb/IIIa RA studies - used by practicing interventionalists Bleeding ACC/AHA guidelines, JACC 2001 Tolleson TR et al., JACC 41:386-93, 2003
  5. 5. Is bivalirudin superior to UFH? • In a randomized comparison, bivalirudin was not superior to UFH in thrombus containing lesions Heparin (n=266) Bivalirudin (n=301) Incidence (%) 15 14,6 12,4 10 4,9 5,3 5 1,9 2,0 0,4 1,0 0 6,8 7,0 Death MI Emergency CABG Death, MI, Bypass Surgery Abrupt Closure *Shah, et al. J Am Coll Cardiol 1997:1264-1269.
  6. 6. Is bivalirudin superior to UFH? (without IIb/IIIa) ISAR REACT 3 Cumulative incidence of Primary EP of Death, MI, UR, MB(%) 10 RR=0.94 [95% CI, 0.77-1.15], P=0.57 UFH 8 Bivalirudin 8.7% 8.3% 6 P=0.008 ) % ( 4 e id c n I 2 UFH = 140 IU/kg 0 0 5 10 15 20 Days after randomization 25 30 Kastrati A et al. NEJM 2008
  7. 7. ACUITY PCI Is bivalirudin superior to UFH? (with GP IIbIIIa inh.) Stone GW et al. Lancet 2007;369:907-19
  8. 8. In high risk PCI 1. In head-to head comparisons, bivalirudin is never more effective or safer than UFH at the dose recommended by the guidelines 2. In asymetrical comparisons (with inappropriate use of GPIs in control patients) bivalirudin is safer in studies with femoral access only.
  9. 9. Bivalirudin is the ideal anticoagulant therapy in high risk PCI and following ACS
  10. 10. A cath lab drug that costs a lot and cannot be used alone… Ambulance Fondaparinux LMWH UFH ER Cath Lab Bivalirudin Ward Fondaparinux LMWH UFH
  11. 11. Bivalirudin is the ideal anticoagulant therapy in high risk PCI and following ACS Meaning primary PCI?
  12. 12. HORIZONS : primary PCI STEMI ≤12 hours Aspirin, thienopyridine, UFH R 1:1 UFH + GP IIb/IIIa inhibitor (abciximab or eptifibatide) Bivalirudin monotherapy (± provisional GP IIb/IIIa) Emergent angiography, followed by triage to… CABG – Primary PCI – Medical Rx NACE and MB at 30 days Stone GW et al. N Engl J Med. 2008;358:2218-30
  13. 13. The dazzling effect of mortality reduction (« p values are no substituent for a brain ») 30d Mortality (all cause): 2.1% vs 3.1% – Low risk population – 3.1% in the control arm, absolute difference for death of 1%  power: 48%  Blinding effect of mortality reduction?
  14. 14. A cath lab drug that costs a lot and should not be used alone! Dangas GD et al. Circulation. 2011;123:1745-1756
  15. 15. HORIZONS The study was powered to demonstrate superiority of bivalirudin without GPIIbIIIa over UFH with GPIIbIIIa, on major bleeding and NACE at 30 days.
  16. 16. Hematomas of at least 5 cm and outcomes in patients undergoing PCI « Hematomas > 5 cm have no effect on 30day ischemic outcome and 1-year mortality in patients undergoing PCI» ! HD White et al. Am Heart J 2010;159:110-6
  17. 17. A cath lab drug that costs a lot for nothing if you use radials! Transradial: n=200 !
  18. 18. In primary PCI 1. In the real world, GPIs are used selectively in high risk patients (not systematically as in the controls of HORIZONS) 2. Bivalirudin does not protect your patients well against ischemic events 3. Bivalirudin safety claim is not appropriate for radial centers
  19. 19. One poorly convincing trial  wait for the next Please wait for TCT 2013
  20. 20. … and the next! N=6800
  21. 21. If you already use bivalirudin… check the dose with your nurses! Needs an IV infusion No antidote Complex dosing • Elective: Bolus 0.75 mg/kg and infusion of 1.75 mg/kg/h • NSTE-ACS pre-lab: Bolus 0.1 mg/kg and infusion of 0.25 mg/kg/h • NSTE-ACS in-lab: Bolus of 0.5 mg/kg and infusion of 1.75 mg/Kg/h • Primary PCI: Bolus 0.75 mg/kg and infusion of 1.75 mg/kg/h • Post-primary PCI: infusion of 0.25 mg/kg/h
  22. 22. Conclusions 1. If you do not use GPIIbIIIa inhibitors  bivalirudin is not for you 2. If you do not use UFH  bivalirudin is not for you 3. If you still use UFH and IIbIIIa inhibitors and you want to reduce bleeding  think radial first 4. If you still use UFH and IIbIIIa inhibitors and you want to replace GPIIbIIIa inhibitors  think prasugrel/ticagrelor first 5. If you still use UFH and IIbIIIa inhibitors and you want to replace UFH  think of less expensive options Finally, do not forget that bivalirudin is a cath lab drug but patients just cross the cath lab Slides available at www.action-coeur.org
  23. 23. Controversies in antithrombotic therapy Bivalirudin is the ideal anticoagulant therapy in high risk PCI and following ACS G. Montalescot www.action-coeur.org
  24. 24. God we trust. Others bring your own data!
  25. 25. The reality is that nobody uses bivalirudin in Europe! • ACCOAST presented tomorrow at 2.00pm at the hotline II session • NSTEMI undergoing PCI in Europe (19 countries) • Anticoagulants: Antithrombin Use UFH LMWH Fondaparinux Bivalirudin % 65 30 4.3 0.7
  26. 26. Meta-analysis enoxaparin vs. UFH  34%  48% J. Silvain et al. BMJ 2012
  27. 27. ATOLL : primary PCI Randomization as early as possible (MICU +++) Real life population (shock, cardiac arrest included) No anticoagulation and no lytic before Rx Similar antiplatelet therapy in both groups STEMI  Primary PCI UFH IV ENOXAPARIN IV 0.5 mg/kg 50-70 IU with GP IIbIIIa 70-100IU without GP IIbIIIa (Dose ACT-adjusted) with or without GPIIbIIIa Primary PCI UFH IV or SC ENOXAPARIN SC 30 days 1° EP: Death, Complication of MI, Procedure Failure, Major Bleeding Main 2° EP: Death, recurrent MI/ACS, Urgent Revascularization Montalescot G, et al. Lancet. 2011;378:693-703
  28. 28. ATOLL: enox IV vs. UFH IV in pPCI Primary Endpoint Death, Complication of MI, Procedure Failure or Major Bleeding Main Secondary Endpoint (ischemic) Death, Recurrent ACS or Urgent Revascularization Montalescot G, et al. Lancet. 2011;378:693-703
  29. 29. ATOLL: Primary end point Death, Complication of MI, Procedure Failure or Major Bleeding Intent-To-Treat Per-protocole RRR = 23% P = 0.01 Montalescot G, et al. Lancet. 2011 Collet JP et al. Am J cardiol 2013
  30. 30. Mortality in ATOLL Per-protocole Intent-To-Treat RRR = 40% P = 0.08 Montalescot G, et al. Lancet. 2011;378:693-703 RRR = 64% P = 0.003 Collet JP et al. ESC 2012

×