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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
No conflict of interest
Which heparin should we use early after mechanical prosthetic
valve replacement ?
ACC/AHA guidelines1
The use of heparin early after prostheticvalve replacement before warfarin achievestherapeutic 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.
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.
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 ?
Medico-legal paradox in the choice of the heparin (LMWH or
UH)
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
In the early period after MeHVR, a first pilot study with LMWH3.
• Montalescot study3 :• 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
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 data4
(4) Fanikos J, et al. Am J Cardiol 2004; 93 : 247-50.
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
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
Target INRPOCRC 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
Results
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
0
10
20
30
40
50
60
70
80
D 3-5 D 5-10 D 11-15 D 16-20 D 21-25 D > 25
LMWH beginning time
Pat
ien
ts (
n)
Patients Included : n = 250
16 ± 11 days after surgery
VKA treatment :
-started before inclusionn = 190INR = 1.5± 0.4
-started at inclusionn = 60
• 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)
Thromboembolic risk factors
•Age > 70 20.4 %•Hypertension 40%•LVEF < 45 % 11.6 %•Prior ischemic stroke, 12.4 %•Atrial fibrillation 50 %•Enlarged LA (LAD > 45 mm) 53.2 %•Redo cardiac Surgery 19%•Diabetes 13%•MVR 13.6%•DVR 10.4 %90 % of the patients had at least one risk factor, 61% two and 24 % three or more
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…)
Results : clinical outcomes
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
3 months follow-up
• N = 247 (98.8 %)
• 1 transient ischaemic attack– Normal transoesophagal echocardiography– 70 % carotid stenosis
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
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 surgery5.6
• 3°) Early post operative period after IV line withdrawal :
• Our study
5. Kovacs MJ et al. Circulation 2004; 110: 1658-636. Douketis JD. Arch Intern Med 2004; 164(12): 1319-26.