1 / 26

Extract: Protocol Design

Extract: Protocol Design. STEMI < 6 h Lytic eligible. Lytic choice by MD (TNK, tPA, rPA, SK). ASA. Double-blind, double-dummy. ENOX < 75 y: 30 mg IV bolus SC 1.0 mg / kg q 12 h (Hosp DC) ≥ 75 y: No bolus SC 0.75 mg / kg q 12 h (Hosp DC ) CrCl < 30: 1.0 mg / kg q 24 h.

marilu
Download Presentation

Extract: Protocol Design

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. Extract: Protocol Design STEMI < 6 hLytic eligible Lytic choice by MD(TNK, tPA, rPA, SK) ASA Double-blind, double-dummy ENOX < 75 y: 30 mg IV bolus SC 1.0 mg / kg q 12 h (Hosp DC) ≥ 75 y: No bolusSC 0.75 mg / kg q 12 h (Hosp DC) CrCl< 30: 1.0 mg / kg q 24h UFH60 U / kg bolus (4000 U) Inf 12 U / kg / h (1000 U / h)Duration: at least 48 hCont’d at MD discretion Day 301° Efficacy Endpoint: Death or Nonfatal MI1° Safety Endpoint: TIMI Major Hemorrhage Antman EA et al. NEJM 2006;354

  2. ExTRACT-TIMI 25: Primary End Point (ITT) Death or Nonfatal MI UFH 12.0% 17% RRR 9.9% Enoxaparin Primary End Point (%) Relative Risk0.83 (95% CI, 0.77 to 0.90)P<.001 Lost to follow-up = 3 Days after Randomization Adapted with permission from Antman EM, et al. N Engl J Med. 2006;354:1477-1488.

  3. Bleeding Endpoints (TIMI) 30 Days UFH ENOX ARD 0.7%RR 1.53P<0.0001 ARD 0.4%RR 1.39P = 0.014 ARD 0.1%RR 1.27P = 0.14 % Events Major Bleed(fatal + nonfatal) NonfatalMajor Bleed ICH Antman EA et al. NEJM 2006;354

  4. Major Hemorrhagic Events (Acute Phase) No significant increase in rate of major hemorrhage 60 Number of patients NS UFH Enoxaparin 40 NS NS 20 0 ESSENCE n = 3171 TIMI 11B n = 3910 TESSMA n = 7081 UFH, unfractionated heparin; NS, not significant Antman EM et al. Circulation 1999;100:1602-8

  5. Severe / moderate hemorrhage Death or re-MI Abciximab + 7.4% 4.6% reteplase D = 2.3% P < 0.001 D = 1.4% P = 0.001 8.8% Reteplase 2.3% 6 4 2 0 2 4 6 8 10 Percentage of patients GUSTO V Benefit vs. risk GUSTO V Investigators. Lancet. 2001;357:1905.

  6. Low-Molecular-Weight Heparin Advantages Disadvantages • Increased anti-Xa to anti-IIa activity  inhibits thrombin generation more effectively • Induces ↑ release of TFPI vs UFH • Not neutralized by platelet factor 4 • Less binding to plasma proteins (eg, acute-phase reactant proteins)  more consistent anticoagulation • Lower rate of HIT vs UFH • Lower fibrinogen levels • Easy to administer (SC administration) • Long history of clinical studies and experience, FDA-approved indications • Monitoring typically unnecessary • Indirect thrombin inhibitor • Less reversible • Difficult to monitor(no aPTT or ACT) • Renally cleared • Long half-life • Risk of HIT Hirsh J, et al. Circulation. 2001;103:2994-3018. TFPI = tissue factor pathway inhibitor; UFH = unfractionated heparin; SC = subcutaneous; aPTT = activated partial thromboplastin time; ACT = activated coagulation time.

  7. IIa C AT IIa S Hep UFH Direct antithrombin AT Xa LMWH

  8. Clot Burden in ACS patient

  9. Heparin fails to effectively inhibit Clot-bound Thrombin

  10. Bivalirudin inhibits Clot-Bound and Circulating Thrombin

  11. Bivalirudin Does not activate Platelets

  12. Bivalirudin: Unique mechanism of action overcomes the limitation of Heparin

More Related