Low Molecular Weight Heparin as bridging anticoagulant early after mechanical heart valve replacement.

1
Low Molecular Weight Heparin as bridging
anticoagulant early after mechanical heart valve
replacement. P Meurin, JY Tabet, A Ben Driss, H
Weber, N RenaudLes Grands Prés
2
No conflict of interest
3
Which heparin should we use early after
mechanical prosthetic valve replacement ?
 
4
ACC/AHA guidelines1

•  It is important to note that thromboembolic
• risk is increased early after insertion of the
• prosthetic valve.

• The use of heparin early after prosthetic
• valve replacement before warfarin achieves
• therapeutic levels is controversial  

(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 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

LMWH
UH
day 2
(3)Montalescot G, et al.Circulation 2001 101
1083-86.
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 
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 lt150µm/l),
  heparin induced thrombocytopenia, pregnancy.
• Follow-up 3 months after LMWH withdrawal

13
Anticoagulation management

• Monitoring
• INR three times a week
• Platelet count twice a week
• Anti Xa activity in
• Obese patients (BMI gt30)

• 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 gt150 n 16
• Suspected HIT n 4

16
Patients Included n 250

• VKA treatment
• -started before inclusion
• n 190
• INR 1.5 0.4
• -started at inclusion
• n 60

16 11 days after surgery
17
Patients Characteristics (n 250)

• 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

• 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

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Thromboembolic risk factors

• Age gt 70 20.4
• Hypertension 40
• LVEF lt 45 11.6
• Prior ischemic stroke, 12.4
• Atrial fibrillation 50
• Enlarged LA (LAD gt 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

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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 surgery5.6
• 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.