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.