Enoxaparin Anticoagulation Monitoring in the Cath- Lab Using a New Bedside Assay

1. Enoxaparin Anticoagulation Monitoring in the Cath- LabUsing a New Bedside Assay Johanne Silvain, Farzin Beygui, Annick Ankri, Anne Bellemain-Appaix, Ana Pena, Olivier Barthelemy, Guillaume Cayla, Vanessa Gallois, Sophie Galier, Dominique Costagliola, Jean-Philippe Collet, Gilles Montalescot Silvain J et al . JACC 2010; 55:617

2. Funding - Disclosures Funding of the study • This study was supported in part by INSERM (Institut National de la Santé et de la Recherche Médicale) and by International Technidyne Corporation (ITC) Edison, NJ, U.S.A. Dr Silvain Disclosure = Research Grant • BMS, Daiichi-Sankyo, Eli Lilly, Sanofi-Aventis

3. Enoxaparin in guidelines ESC 2008 ACC/AHA 2007 Elective PCI Ø STEEPLE Ø 0.5mg IV bolus META-ANALYSIS (Dumaine et al) Non-ST ACS IIa-B I-A Invasive (urgent/early) 1mg/kg/12H SC I-A Conservative I-B STEMI ATOLL ? Primary PCI Ø Ø 0.5mg IV bolus I-B after enoxaprin I-A IIa-B (sk) I-A Fibrinolysis

4. Aim of the study • to evaluate the ability of the Hemonox assay to identify in the cath-lab patients with insufficient enoxaparin anticoagulation before PCI • = low anti-Xa activity level <0.5 IU/mL measured by chromogenic reference technique Patients at High Risk of ischemic complications Montalescot G. Circulation 2004;110:392-8.

5. A new bedside test HEMONOXTM assay International Technidyne Corporation (ITC), NJ, US El Rouby S. J Thromb Thrombolysis (2006) 21: 137–145 <25 μl of whole blood per test HEMONOX Clotting Time (seconds)

6. Enoxaparin Protocol

7. Flow chart 313 patients entered the study 11 patients did not received any enoxaparin 6 patients were on oral anticoagulant (vit-K antagonist) 296 patients went through analysis 211 patients = IV ENOX 64 patients = SQ ENOX 21 patients = SQ + IV ENOX 14 patients = treatment unknown 9 patients were lost on Fup 287 patients had a complete Fup

8. Patients characteristics

9. optimal anticoagulation in 95% of patients 4.7 % Patients at High Risk of ischemic complications ! The distribution of anti-Xa levels 1.8 Median Anti-Xa Level T1 = 0.1 IU/mL [0.1-0.1] T2 = 0.87 IU/mL [0.74-1.03] 0.5

10. Evaluation of the Hemonox CT AUC Hemonox CT: 0.95 ±0.01 95% Cl 0.93–0.97; p<0.0001 AUC aPTT: 0.89 ±0.01 95% Cl 0.86-0.92; p<0.0001 Delong & Delong diff = 0.06* 95% CI 0.03-0.09; *p<0.0001

11. 83% Accuracy (95% CI 80-86) 94.9% Se (95% CI 91-97) 73.3% Spe (95% Cl 68-79) Hemonox CT >120 sec Detection of AntiXa <0.5 IU/mL AntiXa ≥0.5 IU/mL AntiXa <0.5 IU/mL

12. MACCE * n=13 (4.5%) at 30 days Death n=3 (1.0%) * Death + MI + uTVR + Stroke Clinical Outcomes and Safety Bleeding rate = 2 major bleedings (0.66%) ( both anti-Xa level <1.2 IU/ml) p=0.9 157 p=0.3 139 0.87 0.76

13. Limitations 1- not powered to assess the impact of the Hemonox CT on clinical outcomes 2- Limited information obtained on high levels of anticoagulation as very few patients (n=3) reached anti-Xa values > 1.8 IU/ml 3- the cost-effectiveness of a monitoring guided strategy of enoxaparin anticoagulation has not been evaluated

14. 2- High risk patients (anti-Xa activity <0.5 IU/ml) can be reliably identified Montalescot G. Circulation 2004;110:392-8. 3- Hemonox CT can ensure that an adequate anticoagulation level is present before PCI and avoid stacking and overdosing with UFH Ferguson JJ. SYNERGY trial. JAMA 2004;292:45-54. Conclusion (1/2) 1- Hemonox CT is an easy to usebedside test able to rapidly monitor enoxaparin anticoagulation in patients undergoing PCI 4- The test can be seen as a tool for tailored enoxaparin therapy in the cath-lab

15. How to use Hemonox test in cath-lab ? Conclusion (2/2) Patients is well anticoagulated PCI Right in 94.8% 120 sec Patients is under anticoagulated additional IV bolus of 0.5 mg/kg enoxaparin Right in 73.3%