Post on 12-Nov-2014
description
Optimal duration of venous thrombosis treatment
Sabine EichingerDiv. of Hematology and HemostasisMedical University of Vienna, Austria
Treatment of venous thromboembolism (VTE)
acute subacute chronic
2 weeks up to 3 - 6 months > 6 months
Heparin Vitamin K antagonists
acute subacute extendedRivaroxaban
2 weeks up to 3 - 6 months > 6 months 2 weeks up to 3 - 6 months
Treatment of VTE
Months since randomization
Recu
rrence
ris
k (%
)
Schulman, N Eng J Med 2013
Placebo
Anticoagulant
R
OAC ~ 6 mo
VTE
Take home!
• Considerable risk of recurrent VTE after stopping anticoagulation
Recurrence risk after VTE
Recurrence risk after VTE
Pro
babili
ty o
f re
curr
ence
(%
)
Years after anticoagulation0 1 2 5 63 4
0
40
20
10
30
50
Baglin, J Thromb Haemost 2010
Recurrence risk after VTE
Location of VTE
PE (+DVT) Proximal DVT
Distal DVT
Recurrence (95% CI)
Year 1 7.4% (5.7-9.5) 8.4% (6.9-10.2) none
Year 5 22% (16.3-29.8) 26.4% (20.5-34.1) 7.6% (3.0-18.9)
Initial Diagnosis
Iorio, Arch Int Med 2010
Transient risk factor
Recurrence risk after VTE
3.3%/year
Prandoni, Blood 2002
Cancer patients
Recurrence during VKA
Anticoagulation after VTE
Major bleeding during VKA
Cancer patients
Anticoagulation after VTE
LMWH for 6 months
Complete remission + no additional risk
factors
ChemotherapyInterventions
Stable diseasePatient‘s
preference
Stop anticoagulation LMWH Oral anticoagulants
Active cancer ±additional risk factors
Take home!
• Considerable risk of recurrent VTE after stopping anticoagulation
• Cancer patients are at high risk of recurrent VTE and bleeding
• Provoked VTE low risk (~3%/yr)
Unprovoked VTE
Kyrle & Eichinger, Lancet 2010
Recurrence risk after VTE
Take home!
• Considerable risk of recurrent VTE after stopping anticoagulation
• Cancer patients are at high risk of recurrent VTE and bleeding
• Provoked VTE low risk (~3%/yr) • Unprovoked VTE high risk (up to 15%/yr)
Treatment of VTE
Months since randomization
Recu
rrence
ris
k (%
)
Schulman, N Eng J Med 2013
Placebo
Anticoagulant
R
OAC ~ 6 mo
VTE
Linkins, Ann Intern Med 2003
Time period of AC
Major bleeding (%, 95% CI)
Intracranial bleeding(%, 95% CI)
Initial 3 months 2.06 (2.04-2.08) 1.48 (1.40–1.56)
> 3 months 2.74 (2.71-2.77)/yr 0.65 (0.63–0.68)/yr
Bleeding during anticoagulation for VTE
Case fatality rate after 3 mo 9.1% (95% CI 2.5–21.7%)
Take home!
• Considerable risk of recurrent VTE after stopping anticoagulation
• Cancer patients are at high risk of recurrent VTE and bleeding
• Provoked VTE low risk (~3%/yr) • Unprovoked VTE high risk (up to 15%/yr)• Low recurrence risk during anticoagulation• Risk of bleeding
Treatment of VTE
Months since randomization
Recu
rrence
ris
k (%
)
Schulman, N Eng J Med 2013
Placebo
Anticoagulant
R
OAC ~ 6 mo
VTE
Duration of anticoagulation
Boutitie, BMJ 2011
Recurrence risk after VTE
6 12 18 months
Take home!
• Considerable risk of recurrent VTE after stopping anticoagulation
• Cancer patients are at high risk of recurrent VTE and bleeding
• Provoked VTE low risk (~3%/yr) • Unprovoked VTE high risk (up to 15%/yr)• Low recurrence risk during anticoagulation• Risk of bleeding• Recurrence risk increases as soon as anticoagulation is
stopped regardless of previous duration
Take home!
• Considerable risk of recurrent VTE after stopping anticoagulation
• Cancer patients are at high risk of recurrent VTE and bleeding• Provoked VTE low risk (~3%/yr) • Unprovoked VTE high risk (up to 15%/yr)• Low recurrence risk during anticoagulation• Risk of bleeding• Recurrence risk increases as soon as anticoagulation is
stopped regardless of previous duration• The case/fatality rate of recurrence is low (<5%)• The case/fatality rate of severe bleeding while on
anticoagulants is high (~10%)
Management of patients with unprovoked VTE
• Identifying patients with low recurrence risk– Thrombophilia screening
Risk factors of recurrence
HR 95% CI
Laboratory abnormality Any vs. none
1.4 0.9 - 2.3
Men vs. women 2.7 1.8 - 4.2
Idiopathic vs. provoked
1.9 1.2 - 2.9
Christiansen, JAMA 2005
no RF1 RF2 RF3 RF4 RF
Risk factors (RF) in 158 pts with a second VTE
35%24%
40%
factor V Leiden, factor II G20210A, HHC, high factor VIII or IX
Kyrle & Eichinger, Lancet 2010
Management of patients with unprovoked VTE
• Identifying patients with low recurrence risk– Thrombophilia screening
– Residual vein thrombosis
Management of patients with unprovoked VTE
• Identifying patients with low recurrence risk– Thrombophilia screening
– Residual vein thrombosis
– D-Dimer
– Prediction models
Nomogram to predict recurrence: Vienna Prediction ModelEichinger, Circulation 2010
Management of patients with unprovoked VTE
• Identifying patients with low recurrence risk
• Alternative antithrombotic concepts
Direct oral anticoagulants
EINSTEINextEinstein Inv.NEJM 2010
AMPLIFYext
Agnelli NEJM 2012
RE-SONATE
SchulmanNEJM 2013
RE-MEDYSchulmanNEJM 2013
Patients, n
1197 2486 1343 2856
Study drug
Rivaroxaban1 x 20 mg
Apixaban2 x 5 mg
2 x 2.5 mg
Dabigatran2 x 150 mg
Dabigatran
2 x 150 mg
Control Placebo Placebo Placebo Warfarin
Recurrent VTE and related death
EINSTEINext - secondary prevention of VTE
EINSTEIN Investigators, N Engl J Med 2010
Agnelli, N Eng J Med 2013
Recurrent VTE and related death
AMPLIFYext - secondary prevention of VTE
RESONATE - secondary prevention of VTE
Recurrent VTE and related death
Schulman, N Eng J Med 2013
REMEDY - secondary prevention of VTE
Recurrent VTE and related death
Schulman, N Eng J Med 2013
Patients, n (%) Hazard Ratio (95% CI)
Rivaroxaban Placebo
36 (6.0)7 (1.2)
5.19 (2.3 – 11.7)
Apixaban 2.5 mg 5.0 mgPlacebo
27 (3.2)35 (4.3)22 (2.7)
1.20 (0.69 – 2.10)
1.62 (0.96 – 2.73)
Dabigatran Placebo
36 (5.3)12 (1.8)
2.92 (1.52 – 5.60)
Dabigatran Warfarin
80 (5.6)145 (10.2)
0.54 (0.41 – 0.71)
Major and clinically relevant non major bleeding
Aspirin for longterm prophylaxis of VTE
Brighton, N Engl J Med 2012
Anticoagulation after venous thrombosis
3 months long term
distal DVT provoked* VTE
unprovoked VTE
stop: bleeding risk recurrence risk
alternative: rivaroxaban aspirin
* Surgery, trauma, immobilisation, pregnancy/puerperium, female hormone intake, long haul travel
AWMF online, 6/20109th ACCP Consensus Conference on Antithrombotic Therapy; Kearon, Chest 2012