Extended Anticoagulation in VTE

Geoffrey Barnes, MDCardiovascular and Vascular Medicine

University of Michigan, USA

1st Qatar Conference on Safe Anticoagulation Management

February 27, 2015

Outline

• VTE Recurrence Risk• Patient Selection for Extended Therapy• Medication Selection for Extended Therapy• My Approach

Definitions

• Venous Thromboembolism (VTE)– Deep Venous Thrombosis (DVT)– Pulmonary Embolism (PE)

• Treatment Phases– Acute/Initial – first few days– Intermediate/Long-term – up to 3-6 months– Chronic/Extended – beyond first 3-6 months

• Provoked– Transient surgical procedure– Immobilization– Pregnancy or Hormone-related (e.g estrogen

contraceptives)

Lancet. 2012; 379: 1835-1846

Clinical Case

• 65 year old man with CAD and a first unprovoked femoral-popliteal DVT

• Completed 3 months of warfarin therapy

• What is his recurrence risk?• Does he need further therapy?• If so, what is the best medication to use?

Outline

• VTE Recurrence Risk• Patient Selection for Extended Therapy• Medication Selection for Extended Therapy• My Approach

Provoked vs Unprovoked

BMJ. 2011; 342:d3036

Provoked vs Unprovoked

Surgically Provoked

Non-surgically Provoked

Unprovoked Cancer-related0

5

10

15

20

25

0.7

4.2

7.4

20.7

Recu

rren

ce R

isk (%

)

Arch Int Med 2010;170:1710-1716Blood 2002; 100:3484-8

VTE Location

BMJ. 2011; 342:d3036

HR 0.49 (0.34-0.71)

Age and Obesity

Arch Intern Med. 2000;160(6):761-8

Gender

NEJM 2004;350:2558-2563

D-Dimer

Positive D-Dimer 8.9%/year

Negative D-Dimer 3.5%/year

Ann Intern Med. 2008;149:481-490

D-Dimer

Kearon Ann Int Med 2015;162:27

3%

97%

15%85%

D-Dimer

Blood 2010; 115: 481–488CMAJ 2008; 179: 417–426

On Anticoagulation

Negative D-Dimer

Positive D-Dimer

28%

4 weeks without Anticoagulation

Hypercoagulable States

• Factor V Leiden• Protein C/S Deficiency• Antithrombin Deficiency• Elevated Homocysteine• Dysfibrinogenemia• Antiphospholipid Antibodies

Hypercoagulable States

• Considerations– How significant is the increased VTE recurrence

risk?– How frequently is the hypercoagulable state

found?– Can testing be done on anticoagulation?– Are there treatment implications?

Blood 2013;122:817-824Circulation 2014;130:283-287

Hypercoagulable States

• Factor V Leiden• Protein C/S Deficiency• Antithrombin Deficiency• Elevated Homocysteine• Dysfibrinogenemia• Antiphospholipid Antibodies– VTE Recurrence Risk (RR ~2)– Favor use of Warfarin over DOACs currently

Blood 2013;122:817-824Circulation 2014;130:283-287

Outline

• VTE Recurrence Risk• Patient Selection for Extended Therapy• Medication Selection for Extended Therapy• My Approach

VTE Recurrence Predictors

• Provoked vs Unprovoked• PE and Proximal DVT vs Distal DVT• Age• Obesity• Gender• D-dimer• Hypercoagulable States

Risk Prediction Models

CMAJ 2008;179:417-426Circulation 2010; 121:1630-1636J Thromb Haemost 2012; 10: 1019–1025

Men and HERDOO

Vienna Risk Model

DASH

Gender X X XD-Dimer X X X

Signs of Post-Thrombotic Syndrome

X

Obesity XAge X

Location of DVT/PE XProvoked? X

Men and HERDOO-2

High Risk:• All Men• Women with 2+ of• Post-thrombotic

Syndrome• Elevated D-dimer• Obesity

75% of patients are High Risk

Freedom from Recurrent VTE

CMAJ 2008;179:417-426

Outline

• VTE Recurrence Risk• Patient Selection for Extended Therapy• Medication Selection for Extended Therapy• My Approach

Medication Options

• Warfarin• Dabigatran• Rivaroxaban• Apixaban• Aspirin

Warfarin

NEJM 2003;348:1425-1434 and NEJM 2003;349:631-639

Dabigatran

Recurrent VTE Any Bleeding

NEJM 2013;368:709-718

War

farin

Plac

ebo

Rivaroxaban

NEJM 2010;363:2499-2510

Apixaban

Recurrent VTE Major and CRNM Bleeding

NEJM 2012;368:699-708

Aspirin

INSPIRE Collaborative (WARFASA & ASPIRE)

Circulation 2014;130:1062-1071

VTE Recurrence Risk

NEJM 2003;348:1425-1434. NEJM 2003;349:631-639. NEJM 2013;368:709-718. NEJM 2010;363:2499-2510 NEJM 2012;368:699-708. NEJM 2012;368:699-708. Circulation 2014;130:1062-1071

Outline

• VTE Recurrence Risk• Markers of Recurrence Risk• Patient Selection for Extended Therapy• Medication Selection for Extended Therapy• My Approach

My Approach

Barnes GD Vascular Medicine 2015 (in press)

Predictive Factors:• Provoked• D-Dimer• Gender

My Approach

• Drug Selection– Another indication?• Example: Aspirin for CAD

– Prefer to continue current medication?– Balance efficacy and risk• Usually use apixaban or rivaroxaban

Clinical Case

• 65 year old man with CAD and a first unprovoked femoral-popliteal DVT

• Completed 3 months of warfarin therapy

• What is his recurrence risk?– High: >7-10% per year

• Does he need further therapy?– Yes

• If so, what is the best medication to use?– Apixaban or Rivaroxaban if CAD stable– Aspirin if recent PCI or MI requiring clopidogrel

Thank You

Louzada/Ottawa Score

Risk Factor Point Number of Points

VTE Recurrence Risk (per year)

Female 1 ≤0 ≤5%Lung Cancer 1 1 13-16%Prior VTE 1 2 18%Breast Cancer -1 3 25-50%TNM Stage = I -2

Cancer-associated VTE

Circulation 2012;126:448-454