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Anticoagulation therapy for DVT & PE: How long and how intense? Marc Schindewolf Division of Angiology Swiss Cardiovascular Center Bern University Hospital

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Page 1: Anticoagulation therapy for DVT & PE: How long and how ......Seligsohn U et al, N Engl J Med 2001, Baglin T et al, Lancet 2003, Christiansen SC et al, JAMA 2005, Middeldorp S et al,

Anticoagulation therapy for DVT & PE:

How long and how intense?

Marc Schindewolf

Division of Angiology

Swiss Cardiovascular Center

Bern University Hospital

Page 2: Anticoagulation therapy for DVT & PE: How long and how ......Seligsohn U et al, N Engl J Med 2001, Baglin T et al, Lancet 2003, Christiansen SC et al, JAMA 2005, Middeldorp S et al,

Anticoagulation therapy for DVT & PE: How long and how intense? Marc Schindewolf 2

Division of Angiology, Swiss Cardiovascular Center, Bern University Hospital

How long….?

Page 3: Anticoagulation therapy for DVT & PE: How long and how ......Seligsohn U et al, N Engl J Med 2001, Baglin T et al, Lancet 2003, Christiansen SC et al, JAMA 2005, Middeldorp S et al,

Anticoagulation therapy for DVT & PE: How long and how intense? Marc Schindewolf 3

Division of Angiology, Swiss Cardiovascular Center, Bern University Hospital

Page 4: Anticoagulation therapy for DVT & PE: How long and how ......Seligsohn U et al, N Engl J Med 2001, Baglin T et al, Lancet 2003, Christiansen SC et al, JAMA 2005, Middeldorp S et al,

Anticoagulation therapy for DVT & PE: How long and how intense? Marc Schindewolf 4

Division of Angiology, Swiss Cardiovascular Center, Bern University Hospital

Page 5: Anticoagulation therapy for DVT & PE: How long and how ......Seligsohn U et al, N Engl J Med 2001, Baglin T et al, Lancet 2003, Christiansen SC et al, JAMA 2005, Middeldorp S et al,

Anticoagulation therapy for DVT & PE: How long and how intense? Marc Schindewolf 5

Division of Angiology, Swiss Cardiovascular Center, Bern University Hospital

Page 6: Anticoagulation therapy for DVT & PE: How long and how ......Seligsohn U et al, N Engl J Med 2001, Baglin T et al, Lancet 2003, Christiansen SC et al, JAMA 2005, Middeldorp S et al,

Anticoagulation therapy for DVT & PE: How long and how intense? Marc Schindewolf 6

Division of Angiology, Swiss Cardiovascular Center, Bern University Hospital

Page 7: Anticoagulation therapy for DVT & PE: How long and how ......Seligsohn U et al, N Engl J Med 2001, Baglin T et al, Lancet 2003, Christiansen SC et al, JAMA 2005, Middeldorp S et al,

Anticoagulation therapy for DVT & PE: How long and how intense? Marc Schindewolf 7

Division of Angiology, Swiss Cardiovascular Center, Bern University Hospital

Page 8: Anticoagulation therapy for DVT & PE: How long and how ......Seligsohn U et al, N Engl J Med 2001, Baglin T et al, Lancet 2003, Christiansen SC et al, JAMA 2005, Middeldorp S et al,

Anticoagulation therapy for DVT & PE: How long and how intense? Marc Schindewolf 8

Division of Angiology, Swiss Cardiovascular Center, Bern University Hospital

Page 9: Anticoagulation therapy for DVT & PE: How long and how ......Seligsohn U et al, N Engl J Med 2001, Baglin T et al, Lancet 2003, Christiansen SC et al, JAMA 2005, Middeldorp S et al,

Anticoagulation therapy for DVT & PE: How long and how intense? Marc Schindewolf 9

Division of Angiology, Swiss Cardiovascular Center, Bern University Hospital

Page 10: Anticoagulation therapy for DVT & PE: How long and how ......Seligsohn U et al, N Engl J Med 2001, Baglin T et al, Lancet 2003, Christiansen SC et al, JAMA 2005, Middeldorp S et al,

Anticoagulation therapy for DVT & PE: How long and how intense? Marc Schindewolf 10

Division of Angiology, Swiss Cardiovascular Center, Bern University Hospital

Page 11: Anticoagulation therapy for DVT & PE: How long and how ......Seligsohn U et al, N Engl J Med 2001, Baglin T et al, Lancet 2003, Christiansen SC et al, JAMA 2005, Middeldorp S et al,

Anticoagulation therapy for DVT & PE: How long and how intense? Marc Schindewolf 11

Division of Angiology, Swiss Cardiovascular Center, Bern University Hospital

Page 12: Anticoagulation therapy for DVT & PE: How long and how ......Seligsohn U et al, N Engl J Med 2001, Baglin T et al, Lancet 2003, Christiansen SC et al, JAMA 2005, Middeldorp S et al,

Anticoagulation therapy for DVT & PE: How long and how intense? Marc Schindewolf 12

Division of Angiology, Swiss Cardiovascular Center, Bern University Hospital

Risk stratification: D-dimers

Prolonged period of D-dimer testing (3 months [d 0,15, 30, 60, 90) after stop of

anticoagulation in patients with first DVT/PE (idiopathic or weak risk factors)

528/1010 (52.3%) patients with negative D-dimers

VTE recurrence 3.0%/y, 95% CI 2.0-4.4 Negative D-dimers

Palareti G et al, Blood 2015

Page 13: Anticoagulation therapy for DVT & PE: How long and how ......Seligsohn U et al, N Engl J Med 2001, Baglin T et al, Lancet 2003, Christiansen SC et al, JAMA 2005, Middeldorp S et al,

Anticoagulation therapy for DVT & PE: How long and how intense? Marc Schindewolf 13

Division of Angiology, Swiss Cardiovascular Center, Bern University Hospital

Risk stratification: D-dimers

Prolonged period of D-dimer testing (3 months [d 0,15, 30, 60, 90) after stop of

anticoagulation in patients with first DVT/PE (idiopathic or weak risk factors)

528/1010 (52.3%) patients with negative D-dimers

Negative D-dimers VTE recurrence 3.0%/y, 95% CI 2.0-4.4

Positive D-dimers,

no anticoagulation VTE recurrence 8.8%/y, 95% CI 5.0-14.1

HR: 2.92, 95% CI 1.9-9.7

p=0.0006

Palareti G et al, Blood 2015

Page 14: Anticoagulation therapy for DVT & PE: How long and how ......Seligsohn U et al, N Engl J Med 2001, Baglin T et al, Lancet 2003, Christiansen SC et al, JAMA 2005, Middeldorp S et al,

Anticoagulation therapy for DVT & PE: How long and how intense? Marc Schindewolf 14

Division of Angiology, Swiss Cardiovascular Center, Bern University Hospital

Risk stratification: Sex differences

Men have about a 50% higher risk than women of recurrent VTE

after stopping anticoagulant treatment.

McRae S et al, Lancet 2006

Page 15: Anticoagulation therapy for DVT & PE: How long and how ......Seligsohn U et al, N Engl J Med 2001, Baglin T et al, Lancet 2003, Christiansen SC et al, JAMA 2005, Middeldorp S et al,

Anticoagulation therapy for DVT & PE: How long and how intense? Marc Schindewolf 15

Division of Angiology, Swiss Cardiovascular Center, Bern University Hospital

Risk stratification: Thrombophilia

Seligsohn U et al, N Engl J Med 2001, Baglin T et al, Lancet 2003, Christiansen SC et al, JAMA 2005, Middeldorp S et al, Ho WK et al, Arch

Int Med 2006, Br J Haematol 2008, Lindhoff-Last E, Haemostaseology 2008, Middeldorp S, Hematology 2011

Page 16: Anticoagulation therapy for DVT & PE: How long and how ......Seligsohn U et al, N Engl J Med 2001, Baglin T et al, Lancet 2003, Christiansen SC et al, JAMA 2005, Middeldorp S et al,

Anticoagulation therapy for DVT & PE: How long and how intense? Marc Schindewolf 16

Division of Angiology, Swiss Cardiovascular Center, Bern University Hospital

Inherited thrombophilias do not appear to play an important role in the

risk of a recurrent thrombotic event.

Hazard ratio 1.5, 95% CI 0.82-2.77; p=0.187

Risk stratification: Thrombophilia

Baglin T et al, Lancet 2003

Page 17: Anticoagulation therapy for DVT & PE: How long and how ......Seligsohn U et al, N Engl J Med 2001, Baglin T et al, Lancet 2003, Christiansen SC et al, JAMA 2005, Middeldorp S et al,

Anticoagulation therapy for DVT & PE: How long and how intense? Marc Schindewolf 17

Division of Angiology, Swiss Cardiovascular Center, Bern University Hospital

Risk stratification: Thrombophilia

Brouwer JLP et al, Thromb Haemost 2009

Anticoagulant deficiency

protein S, protein C, antithrombin

>>Higher risk of recurrent VTE

>> Longer anticoagulation??

Page 18: Anticoagulation therapy for DVT & PE: How long and how ......Seligsohn U et al, N Engl J Med 2001, Baglin T et al, Lancet 2003, Christiansen SC et al, JAMA 2005, Middeldorp S et al,

Anticoagulation therapy for DVT & PE: How long and how intense? Marc Schindewolf 18

Division of Angiology, Swiss Cardiovascular Center, Bern University Hospital

Risk stratification: Residual thrombosis (RVT)

Piovella F et al, Haematolgica 2002 Prandoni P et al, Ann Intern Med 2002

Page 19: Anticoagulation therapy for DVT & PE: How long and how ......Seligsohn U et al, N Engl J Med 2001, Baglin T et al, Lancet 2003, Christiansen SC et al, JAMA 2005, Middeldorp S et al,

Anticoagulation therapy for DVT & PE: How long and how intense? Marc Schindewolf 19

Division of Angiology, Swiss Cardiovascular Center, Bern University Hospital

Risk stratification: Residual thrombosis (RVT)

Piovella F et al, Haematolgica 2002 Prandoni P et al, Ann Intern Med 2002

RVT is a weak overall predictor for recurrent VTE after

unprovoked proximal DVT (HR 1.32, 95% CI: 1.06–1.65)

Association stronger when assessed after three months

(HR 2.17, 95% CI: 1.11–4.25) Donadini MP et al, Thromb Haemost 2014

Page 20: Anticoagulation therapy for DVT & PE: How long and how ......Seligsohn U et al, N Engl J Med 2001, Baglin T et al, Lancet 2003, Christiansen SC et al, JAMA 2005, Middeldorp S et al,

Anticoagulation therapy for DVT & PE: How long and how intense? Marc Schindewolf 20

Division of Angiology, Swiss Cardiovascular Center, Bern University Hospital

Risk stratification: DASH Score

D-dimer positive +2

Age ≤ 50 +1

Sex: male +1

Hormone use - 2

Recurrence risk prediction after first unprovoked proximal DVT or PE

Page 21: Anticoagulation therapy for DVT & PE: How long and how ......Seligsohn U et al, N Engl J Med 2001, Baglin T et al, Lancet 2003, Christiansen SC et al, JAMA 2005, Middeldorp S et al,

Anticoagulation therapy for DVT & PE: How long and how intense? Marc Schindewolf 21

Division of Angiology, Swiss Cardiovascular Center, Bern University Hospital

Risk stratification: DASH Score

Stop anticoagulation

Prolonged

anticoagulation

Tosetto A et al, J Thromb Haemost 2012

Page 22: Anticoagulation therapy for DVT & PE: How long and how ......Seligsohn U et al, N Engl J Med 2001, Baglin T et al, Lancet 2003, Christiansen SC et al, JAMA 2005, Middeldorp S et al,

Anticoagulation therapy for DVT & PE: How long and how intense? Marc Schindewolf 22

Division of Angiology, Swiss Cardiovascular Center, Bern University Hospital

Clinical Characteristic Points

H Hypertension 1

A Abnormal renal and liver function (1 point each) 1 or 2

S Stroke 1

B Bleeding 1

L Labile INR`s 1

E Elderly 1

D Drugs or alcohol (1 point each) 1 or 2

Risk stratification: Bleeding risk

Pisters R et al, Chest 2010

Page 23: Anticoagulation therapy for DVT & PE: How long and how ......Seligsohn U et al, N Engl J Med 2001, Baglin T et al, Lancet 2003, Christiansen SC et al, JAMA 2005, Middeldorp S et al,

Anticoagulation therapy for DVT & PE: How long and how intense? Marc Schindewolf 23

Division of Angiology, Swiss Cardiovascular Center, Bern University Hospital

Therapy….

Page 24: Anticoagulation therapy for DVT & PE: How long and how ......Seligsohn U et al, N Engl J Med 2001, Baglin T et al, Lancet 2003, Christiansen SC et al, JAMA 2005, Middeldorp S et al,

Anticoagulation therapy for DVT & PE: How long and how intense? Marc Schindewolf 24

Division of Angiology, Swiss Cardiovascular Center, Bern University Hospital

f

Page 25: Anticoagulation therapy for DVT & PE: How long and how ......Seligsohn U et al, N Engl J Med 2001, Baglin T et al, Lancet 2003, Christiansen SC et al, JAMA 2005, Middeldorp S et al,

Anticoagulation therapy for DVT & PE: How long and how intense? Marc Schindewolf 25

Division of Angiology, Swiss Cardiovascular Center, Bern University Hospital

Dalteparin vs. warfarin for prevention of recurrent VTE in cancer patients

Rethrombosis rate: 8.8% vs. 15.8%, Hazard ratio 0.48, 95% CI 0.30-0.70, p=0.002)

Dosing: dalteparin 1 x 200 IU/kg/die for 28 days, then 1 x 150 IU/kg/die

Lee AY et al, NEJM 2003

Intensity and duration of anticoagulation: Cancer

C

L

O

STUDY

Page 26: Anticoagulation therapy for DVT & PE: How long and how ......Seligsohn U et al, N Engl J Med 2001, Baglin T et al, Lancet 2003, Christiansen SC et al, JAMA 2005, Middeldorp S et al,

Anticoagulation therapy for DVT & PE: How long and how intense? Marc Schindewolf 26

Division of Angiology, Swiss Cardiovascular Center, Bern University Hospital

Page 27: Anticoagulation therapy for DVT & PE: How long and how ......Seligsohn U et al, N Engl J Med 2001, Baglin T et al, Lancet 2003, Christiansen SC et al, JAMA 2005, Middeldorp S et al,

Anticoagulation therapy for DVT & PE: How long and how intense? Marc Schindewolf 27

Division of Angiology, Swiss Cardiovascular Center, Bern University Hospital

Kearon C et al, Chest 2012; Wells PS et al, JAMA 2014, Kearon C et al, Blood 2015

Page 28: Anticoagulation therapy for DVT & PE: How long and how ......Seligsohn U et al, N Engl J Med 2001, Baglin T et al, Lancet 2003, Christiansen SC et al, JAMA 2005, Middeldorp S et al,

Anticoagulation therapy for DVT & PE: How long and how intense? Marc Schindewolf 28

Division of Angiology, Swiss Cardiovascular Center, Bern University Hospital

How intense….?

Page 29: Anticoagulation therapy for DVT & PE: How long and how ......Seligsohn U et al, N Engl J Med 2001, Baglin T et al, Lancet 2003, Christiansen SC et al, JAMA 2005, Middeldorp S et al,

Anticoagulation therapy for DVT & PE: How long and how intense? Marc Schindewolf 29

Division of Angiology, Swiss Cardiovascular Center, Bern University Hospital

Garcia DA et al, Chest 2012; Kearon C et al, Chest 2012; Heidbuchel H et al, Europace 2013; Dobesh PP et al, Drugs 2014

Page 30: Anticoagulation therapy for DVT & PE: How long and how ......Seligsohn U et al, N Engl J Med 2001, Baglin T et al, Lancet 2003, Christiansen SC et al, JAMA 2005, Middeldorp S et al,

Anticoagulation therapy for DVT & PE: How long and how intense? Marc Schindewolf 30

Division of Angiology, Swiss Cardiovascular Center, Bern University Hospital

Garcia DA et al, Chest 2012; Kearon C et al, Chest 2012; Heidbuchel H et al, Europace 2013; Dobesh PP et al, Drugs 2014

Page 31: Anticoagulation therapy for DVT & PE: How long and how ......Seligsohn U et al, N Engl J Med 2001, Baglin T et al, Lancet 2003, Christiansen SC et al, JAMA 2005, Middeldorp S et al,

Anticoagulation therapy for DVT & PE: How long and how intense? Marc Schindewolf 31

Division of Angiology, Swiss Cardiovascular Center, Bern University Hospital

Garcia DA et al, Chest 2012; Kearon C et al, Chest 2012; Heidbuchel H et al, Europace 2013; Dobesh PP et al, Drugs 2014

Page 32: Anticoagulation therapy for DVT & PE: How long and how ......Seligsohn U et al, N Engl J Med 2001, Baglin T et al, Lancet 2003, Christiansen SC et al, JAMA 2005, Middeldorp S et al,

Anticoagulation therapy for DVT & PE: How long and how intense? Marc Schindewolf 32

Division of Angiology, Swiss Cardiovascular Center, Bern University Hospital

Garcia DA et al, Chest 2012; Kearon C et al, Chest 2012; Heidbuchel H et al, Europace 2013; Dobesh PP et al, Drugs 2014

Page 33: Anticoagulation therapy for DVT & PE: How long and how ......Seligsohn U et al, N Engl J Med 2001, Baglin T et al, Lancet 2003, Christiansen SC et al, JAMA 2005, Middeldorp S et al,

Anticoagulation therapy for DVT & PE: How long and how intense? Marc Schindewolf 33

Division of Angiology, Swiss Cardiovascular Center, Bern University Hospital

Garcia DA et al, Chest 2012; Kearon C et al, Chest 2012; Heidbuchel H et al, Europace 2013; Dobesh PP et al, Drugs 2014

Page 34: Anticoagulation therapy for DVT & PE: How long and how ......Seligsohn U et al, N Engl J Med 2001, Baglin T et al, Lancet 2003, Christiansen SC et al, JAMA 2005, Middeldorp S et al,

Anticoagulation therapy for DVT & PE: How long and how intense? Marc Schindewolf 34

Division of Angiology, Swiss Cardiovascular Center, Bern University Hospital

Garcia DA et al, Chest 2012; Kearon C et al, Chest 2012; Heidbuchel H et al, Europace 2013; Dobesh PP et al, Drugs 2014

Page 35: Anticoagulation therapy for DVT & PE: How long and how ......Seligsohn U et al, N Engl J Med 2001, Baglin T et al, Lancet 2003, Christiansen SC et al, JAMA 2005, Middeldorp S et al,

Anticoagulation therapy for DVT & PE: How long and how intense? Marc Schindewolf 35

Division of Angiology, Swiss Cardiovascular Center, Bern University Hospital

Garcia DA et al, Chest 2012; Kearon C et al, Chest 2012; Heidbuchel H et al, Europace 2013; Dobesh PP et al, Drugs 2014

Page 36: Anticoagulation therapy for DVT & PE: How long and how ......Seligsohn U et al, N Engl J Med 2001, Baglin T et al, Lancet 2003, Christiansen SC et al, JAMA 2005, Middeldorp S et al,

Anticoagulation therapy for DVT & PE: How long and how intense? Marc Schindewolf 36

Division of Angiology, Swiss Cardiovascular Center, Bern University Hospital

Garcia DA et al, Chest 2012; Kearon C et al, Chest 2012; Heidbuchel H et al, Europace 2013; Dobesh PP et al, Drugs 2014

Page 37: Anticoagulation therapy for DVT & PE: How long and how ......Seligsohn U et al, N Engl J Med 2001, Baglin T et al, Lancet 2003, Christiansen SC et al, JAMA 2005, Middeldorp S et al,

Anticoagulation therapy for DVT & PE: How long and how intense? Marc Schindewolf 37

Division of Angiology, Swiss Cardiovascular Center, Bern University Hospital

Garcia DA et al, Chest 2012; Kearon C et al, Chest 2012; Heidbuchel H et al, Europace 2013; Dobesh PP et al, Drugs 2014

Page 38: Anticoagulation therapy for DVT & PE: How long and how ......Seligsohn U et al, N Engl J Med 2001, Baglin T et al, Lancet 2003, Christiansen SC et al, JAMA 2005, Middeldorp S et al,

Anticoagulation therapy for DVT & PE: How long and how intense? Marc Schindewolf 38

Division of Angiology, Swiss Cardiovascular Center, Bern University Hospital

Garcia DA et al, Chest 2012; Kearon C et al, Chest 2012; Heidbuchel H et al, Europace 2013; Dobesh PP et al, Drugs 2014

Page 39: Anticoagulation therapy for DVT & PE: How long and how ......Seligsohn U et al, N Engl J Med 2001, Baglin T et al, Lancet 2003, Christiansen SC et al, JAMA 2005, Middeldorp S et al,

Anticoagulation therapy for DVT & PE: How long and how intense? Marc Schindewolf 39

Division of Angiology, Swiss Cardiovascular Center, Bern University Hospital

Garcia DA et al, Chest 2012; Kearon C et al, Chest 2012; Heidbuchel H et al, Europace 2013; Dobesh PP et al, Drugs 2014

Page 40: Anticoagulation therapy for DVT & PE: How long and how ......Seligsohn U et al, N Engl J Med 2001, Baglin T et al, Lancet 2003, Christiansen SC et al, JAMA 2005, Middeldorp S et al,

Anticoagulation therapy for DVT & PE: How long and how intense? Marc Schindewolf 40

Division of Angiology, Swiss Cardiovascular Center, Bern University Hospital

Page 41: Anticoagulation therapy for DVT & PE: How long and how ......Seligsohn U et al, N Engl J Med 2001, Baglin T et al, Lancet 2003, Christiansen SC et al, JAMA 2005, Middeldorp S et al,

Thank you for your attention

Division of Angiology

Swiss Cardiovascular Center

Bern University Hospital


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