1. Low Molecular Weight Heparin as bridging anticoagulant early after mechanical heart valve replacement. P Meurin, JY Tabet, A Ben Driss, H Weber, N Renaud Les Grands Prés

2. No conflict of interest

3. Which heparin should we use early after mechanical prosthetic valve replacement ?

4. ACC/AHA guidelines 1 The use of heparin early after prosthetic valve replacement before warfarin achieves therapeutic levels is controversial » « It is important to note that thromboembolic risk is increased early after insertion of the prosthetic valve. (1) Bonow RO, Carabello B, de Leon AC et al. ACC/AHA guidelines for the management of patients with valvular heart disease : a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Patients with Valvular Heart Disease). J Am Coll Cardiol. 1998; 32 : 1486-1588.

5. ACCP Guidelines « We suggest administration of UH or LMWH until the INR is stable and at therapeutic levels for 2 consecutive days 2 » Grade 2C (2)Salem DN, Dtein PD, Al-Ahmad A et al. Antithrombotic therapy in valvular heart disease-native and prosthetic. The Seventh Conference on Antithrombotic and Thrombolytic Therapy. CHEST 2004; 126 : 457S-482S.

6. In the real world, Heparin (UH or LMWH) is constantly used before Vitamin K Antagonist treatment achieves therapeutic level after IV line ablation bridge between intravenous Unfractionated Heparin (UH) withdrawal and the time when oral anticoagulation is fully effective : –LMWH or UH ?

7. Medico-legal paradox in the choice of the heparin (LMWH or UH)

8. Medico-legal paradox According to the law –LMWH have no autorisation in this indication According to the science Compared with UH, LMWH are : –As efficient –Safer –More convenient In the literature, LMWH –Have more evidence of efficiency than (at least subcutaneous) UH

9. In the early period after MeHVR, a first pilot study with LMWH 3. Montalescot study 3 : comparison of enoxaparin (n = 102) and calciparin (n = 106) after MeHV replacement Follow up : 2 weeks : same number of thromboembolic and haemorragic events in the two groups (3)Montalescot G, et al.Circulation 2001; 101 : 1083-86. day 2 UH LMWH

10. But as a pilot study, it had some flaws : Retrospective design Small number of patients receiving a LMWH –n = 102 Small number of patients having undergone a mitral valve replacement (n = 10) Short follow up (2 weeks) And the author conclude in pointing out « the need for collection of more clinical data and for randomized trials » 5 years later : not much additional data 4 (4) Fanikos J, et al. Am J Cardiol 2004; 93 : 247-50.

11. Aim of the study Evaluate the feasibility of an LMWH in this indication : –In a prospective study –In a larger population –With a longer follow-up –With a higher number of Mitral Valve Replacement Patients

12. design Prospective monocentric study Selection : –All consecutive patients (from January 2000 to January 2005) in whom MeHVR had been recently performed and transferred to our Post Operative Cardiac Rehabilitation Center (POCRC) Exclusion : –VKA treatment already begun and target INR achieved –Renal insufficiency (creatininemia <150μm/l), heparin induced thrombocytopenia, pregnancy. Follow-up : 3 months after LMWH withdrawal

13. Target INR POCRC arrival LMWH VKA Operation Day 0 UH VKA Monitoring : –INR three times a week –Platelet count twice a week –Anti Xa activity in : Obese patients (BMI >30) Anticoagulation management LMWH : Enoxaparin : 100 iu/kg bid

14. Results

15. Patients Selected : n = 695 Excluded : n = 445 : –VKA treament already fully effective : 425 MVR and DVR : 2.5-3.5 AVR : 2-3 –Creatininemia >150 : n = 16 –Suspected HIT : n = 4

16. Patients Included : n = 250 16 ± 11 days after surgery VKA treatment : -started before inclusion n = 190 INR = 1.5± 0.4 -started at inclusion n = 60

17. Mean age 60 ± 11 Men 60 % LVEF 57 ± 7 % LVEDD 50 ± 7 mm LAD 45 ± mm Mean trans aortic gradient(n = 216) 13 ± 5 mm Hg Mean transmitral gradient(n = 60) 4 ± 1.5 mmHg AVR (n = 190) – AVR alone 128 –AVR + CABG 31 – AVR + Bentall 29 –AVR + Bentall + CABG 2 MVR (n = 34) –MVR alone 21 – MVR + TV 8 – MVR + CABG 5 DVR (n = 26) –DVR alone 21 –DVR + CABG 3 –DVR + Bentall 1 –DVR + TV 1 Patients Characteristics (n= 250)

18. Thromboembolic risk factors Age > 7020.4 % Hypertension40% LVEF < 45 %11.6 % Prior ischemic stroke,12.4 % Atrial fibrillation50 % Enlarged LA (LAD > 45 mm)53.2 % Redo cardiac Surgery 19% Diabetes13% MVR13.6% DVR10.4 % 90 % of the patients had at least one risk factor, 61% two and 24 % three or more

19. Comments High risk population –90 % of the patients had at least one risk factor, 61% two and 24 % three or more –250 (out of 695 patients selected) in whom VKA treatment was not fully effective 16 ± 11 days after surgery Mostly because of post operative complications (pericardial effusion monitoring, pace-maker implantation…)

20. Results : clinical outcomes

21. Prospective intra POCRC follow-up : 20 ± 7 days after LMWH beginning Thromboembolic events :n = 0 Haemorragic events –Major : n = 2 1 tamponade 1 abdominal muscle haematoma requiring blood transfusion –Minor :n = 3

22. 3 months follow-up N = 247 (98.8 %) 1 transient ischaemic attack –Normal transoesophagal echocardiography –70 % carotid stenosis

23. Conclusion : in patients having recently undergone a mechanical heart valve replacement A LMWH therapy as a bridge –From immediate post operative UH cessation –To the time when oral anticoagulation is fully effective seems efficient and safe in preventing thromboembolic events. A randomized study comparing LMWH to UH in this indication is warranted

24. Finally : when could we use LMWH after mechanical heart valve replacement ? 1°) Immediately after surgery : Montalescot study 2°) Temporary interruption of VKA treatment Eg for extracardiac surgery 5.6 3°) Early post operative period after IV line withdrawal : Our study 5. Kovacs MJ et al. Circulation 2004; 110: 1658-63 6. Douketis JD. Arch Intern Med 2004; 164(12): 1319-26.