Venous thromboembolism Treatment and secondary prevention

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Venous thromboembolism Treatment and secondary
prevention These slides were kindly
provided by AstraZeneca
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Venous thromboembolism
DVT
PE
Deep vein insufficiency

Post-thrombotic syndrome
Pulmonary hypertension
Death
Ulcus cruris
Chronic PE
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Deep vein thrombosis
Common femoral vein
Thrombus
Proximal
Knee
Distal
Veins of the leg
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Treatment and secondary prevention of VTE
VTE event
Acute
Continue
Heparin or LMWH together with a VKA (e.g.
warfarin) untill an INR of 2.0-3.0 is achieved
VKA (e.g. warfarin)INR 2.0-3.0
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VTE - treatment options
Acute
Long-term

• Anticoagulation
• - UFH/LMWH
• Thrombolysis
• Thrombectomy
• Inferior vena cava filters (IVCF)

• Anticoagulation- VKAs (e.g. warfarin)- LMWH
• Stockings

6
7th ACCP recommendationsInitial treatment for
acute DVT or PE

• Confirmed DVT or non-massive PE
• Initial treatment with sc LMWH or iv UFH (or sc
  if DVT) Grade 1A for at least 5 days Grade
  1C
• Start VKA with LMWH or UFH on day 1 Grade 1A
• Stop LMWH or UFH when INR stable gt2.0 Grade 1A
• High clinical suspicion of VTE
• Anticoagulation until outcome of diagnostic
  tests Grade 1C

Büller H et al. Chest 2004126401S428S
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Treatment and secondary prevention of VTE
VTE event
Decision point
How long?
Acute
Continue
Heparin or LMWH together with a VKA (e.g.
warfarin) untill an INR of 2.0-3.0 is achieved
VKA (e.g. warfarin)INR 2.0-3.0
3-6-12 months or lifelong
Risk of VTE (5-7/year) vs Risk of bleeding
(3-4/year)
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7th ACCP recommendationsLong term treatment of
acute DVT or PE

• First episode with a transient risk factor
• 3 months after distal or proximal DVT Grade 1A
• At least 3 months after PE Grade 1A
• First episode of idiopathic DVT/PE
• VKA for at least 612 months Grade 1A but
  consider indefinite duration Grade 2A
• Two or more episodes of DVT/PE
• Suggest indefinite treatment Grade 2A
• Target INR 2.5 (range 2.03.0) Grade 1A

Büller H et al. Chest 2004126401S428S
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The dilemma of the long-termtreatment of DVT

• Recurrence rate of VTE in patients with DVT
  dependent on Underlying risk factors for DVT
  Duration of treatment
• Decision regarding duration of treatmentdependent
  on Underlying risk factors for DVT Risk of
  haemorrhage from oral anticoagulation Patient
  preference
• Numerous regimens studied to improve benefit of
  long-term treatment while reducing the dose

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Is there an opportunity to improve the long-term
treatment of VTE?
Recurrence of VTE after stopping oral
anticoagulation
3 months treatment
Event rate()
15
10
5
0
0
3
6
12
24
Months
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Is there an opportunity to improve the long-term
treatment of VTE?
Recurrence of VTE after stopping oral
anticoagulation
3 months treatment
Event rate()
6 months treatment
15
10
5
0
0
3
6
12
24
Months
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Is there an opportunity to improve the long-term
treatment of VTE?
Recurrence of VTE after stopping oral
anticoagulation
3 months treatment
Event rate()
6 months treatment
1 year treatment
15
10
5
0
0
3
6
12
24
Months
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The optimal duration of anticoagulation after a
VTE event evidence from clinical studies
LongOAC
ShortOAC
Reference
No. ofpatients
Followup
Recurrent VTE
Major bleeding
months
months
months
LongOAC
ShortOAC
LongOAC
ShortOAC
DURAC I 897 6 1.5 24 9.5 18.1 1.1 0.2 LAFIT 16
2 27 3 10 1.3 27.4 3.8 0.0 WODIT-DVT 267 12 3
12 3.0 8.3 3.0 0.8 WODIT-PE 326 6-12 3 32.7 4.
1 9.1 1.8 0.0 DOTAVK 539 6 3 15 8.7 8.1 2.6
1.9 DURAC II 227 Indefinite 6 43 2.6 20.7 8.6
2.7
OAC, oral anticoagulation
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Intensity of anticoagulant therapy
Recurrent VTE Cumulative event rate ()
0.25
Placebo - PREVENT
0.20
0.15
Low INR PREVENT
INR 1.5-2.0
0.10
Low INR ELATE
0.05
Conventional INR - ELATE
0.00
INR 2.0-3.0
0
1
2
3
4
Years of follow-up
Ridker PM et al. N Engl J Med 2003
3481425-34 Kearon C et al. N Engl J Med
2003349631-9