Jeddah durationanticoagulation14

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


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


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


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!


• Cancer patients are at high risk of recurrent VTE and bleeding

• Provoked VTE low risk (~3%/yr)

Unprovoked VTE

Kyrle & Eichinger, Lancet 2010


Take home!



• Provoked VTE low risk (~3%/yr) • Unprovoked VTE high risk (up to 15%/yr)

Treatment of VTE


Recu

rrence

ris

k (%

)


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!



• 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


Recu

rrence

ris

k (%

)


Placebo

Anticoagulant

R

OAC ~ 6 mo

VTE

Duration of anticoagulation

Boutitie, BMJ 2011


6 12 18 months

Take home!



• 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!


• 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



– Residual vein thrombosis



– Residual vein thrombosis

– D-Dimer

– Prediction models

Nomogram to predict recurrence: Vienna Prediction ModelEichinger, Circulation 2010


• 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


AMPLIFYext - secondary prevention of VTE

RESONATE - secondary prevention of VTE



REMEDY - secondary prevention of VTE



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

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Jeddah durationanticoagulation14