Anticoagulation therapy for DVT & PE:
How long and how intense?
Marc Schindewolf
Division of Angiology
Swiss Cardiovascular Center
Bern University Hospital
Anticoagulation therapy for DVT & PE: How long and how intense? Marc Schindewolf 2
Division of Angiology, Swiss Cardiovascular Center, Bern University Hospital
How long….?
Anticoagulation therapy for DVT & PE: How long and how intense? Marc Schindewolf 3
Division of Angiology, Swiss Cardiovascular Center, Bern University Hospital
Anticoagulation therapy for DVT & PE: How long and how intense? Marc Schindewolf 4
Division of Angiology, Swiss Cardiovascular Center, Bern University Hospital
Anticoagulation therapy for DVT & PE: How long and how intense? Marc Schindewolf 5
Division of Angiology, Swiss Cardiovascular Center, Bern University Hospital
Anticoagulation therapy for DVT & PE: How long and how intense? Marc Schindewolf 6
Division of Angiology, Swiss Cardiovascular Center, Bern University Hospital
Anticoagulation therapy for DVT & PE: How long and how intense? Marc Schindewolf 7
Division of Angiology, Swiss Cardiovascular Center, Bern University Hospital
Anticoagulation therapy for DVT & PE: How long and how intense? Marc Schindewolf 8
Division of Angiology, Swiss Cardiovascular Center, Bern University Hospital
Anticoagulation therapy for DVT & PE: How long and how intense? Marc Schindewolf 9
Division of Angiology, Swiss Cardiovascular Center, Bern University Hospital
Anticoagulation therapy for DVT & PE: How long and how intense? Marc Schindewolf 10
Division of Angiology, Swiss Cardiovascular Center, Bern University Hospital
Anticoagulation therapy for DVT & PE: How long and how intense? Marc Schindewolf 11
Division of Angiology, Swiss Cardiovascular Center, Bern University Hospital
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
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
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
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
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
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??
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
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
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
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
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
Anticoagulation therapy for DVT & PE: How long and how intense? Marc Schindewolf 23
Division of Angiology, Swiss Cardiovascular Center, Bern University Hospital
Therapy….
Anticoagulation therapy for DVT & PE: How long and how intense? Marc Schindewolf 24
Division of Angiology, Swiss Cardiovascular Center, Bern University Hospital
f
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
Anticoagulation therapy for DVT & PE: How long and how intense? Marc Schindewolf 26
Division of Angiology, Swiss Cardiovascular Center, Bern University Hospital
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
Anticoagulation therapy for DVT & PE: How long and how intense? Marc Schindewolf 28
Division of Angiology, Swiss Cardiovascular Center, Bern University Hospital
How intense….?
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
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
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
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
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
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
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
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
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
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
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
Anticoagulation therapy for DVT & PE: How long and how intense? Marc Schindewolf 40
Division of Angiology, Swiss Cardiovascular Center, Bern University Hospital
Thank you for your attention
Division of Angiology
Swiss Cardiovascular Center
Bern University Hospital