ANTICOAGULATION3 versus 6 months in pts witDVT

or PE or both

Campbell & colleges

BMJ: 31 March,2007

BTS(1992)→3 Mths anticoagulation to pts with pul: VTE(1st episode or no episodes for previous 3 yrs)

UK,N.America,Europe→6 mths or more BTS→compare outcomes of 3 & 6 mths

anticoagulation with warfarin after initial heparin Rx

Methods & Design

Multicentre,prospective,randomised controlled trial with f-up for 1 yr

Mid Sept,1999 to end of Dec,2002 137 Consultants fr 46 hospitals;810 pts >18yr with suspected or proved DVT or

PE or both 369 pts in 3m & 380 in 6mth a/f exclusion

Methods & Design

Start warfarin on day 1 of the scheduled 5 days heparin

F-up at 3,6,& 12 mths from date of entery INR to monitor anticoagulation To acheve INR b/t 2 to 3.5

Methods & Design

Informations obtained

-failure of resolution

-extension or recurrence of DVT or PE

-results of INR

-dates of start & completion of Rx with heparin & warfarin

-adverse events

Methods & Design

Predetermined adverse outcomes

-death from DVT or PE

-failure during Tx

-recurrence a/f end of Tx

-major haemorrhage during Tx

Methods & Design

Type of anticoagulation

-Low MW heparin

-oral anticoag→ warfarin or courmarin Grading for anticoagulation

-good=INR b/t 2 to 3.5 on 2/3 occasions

-mod = 2 to 3.5 on >1/3 but <2/3 occasions

-poor=2 to 3.5 on<1/3 occasions

Methods & Design

Haemorrhage was defined as major if

-transfusion is necessary

-Hb ↓ by 20 g/l

-intracranial or retroperitoneal

-sufficiently serious to stop anticoag

Results

Warfarin Rx at 3m f-up,graded as poor in

-42 of 355 pts in 3mth group(13%)

-37 of 340 pts in 6mth group(11%)

-11(4%) in b/t 3 & 6m →control improved b/t 3 & 6 mths

Results

During Tx →4 pts died from DVT or PE

-1 pt from 3mth group

-3 pts from 6mth group

-1 from 3 mth grp died from DVT or PE 1 mth after completion of Tx

Death fr hge duing Tx →0% for both grp

Results

During & a/f Tx →28 pts died from causes other than DVT & PE

-12 pts from 3m group -16 pts from 6m group DVT or PE failed to resolve,extended or

recurred in -6 in 3m grp without fatal consequences -10 pts in 6m group

Results

Major nonfatal haemorrhage

-0 in 3 mth group

-10 pts in 6 mth group Overall adverse outcomes

-31 pts(8%) in 3 mth group

-35 pts(9%) in 6 mth group

Table showing outcomes at 1 yr

Comparism b/t previous studies & this study

Regarding failure during Tx & recurrence

(1)100 pts with DVT/PE→9 to 17% a/f 6m

(2)1st BTS study(1992) →8% a/f 3 mth

(3)comparing 3 & 6 m Rx →8% in both

(4)comparing 6wk Tx & 6m Tx

-at 2 yrs →18% in 6wk & 9% in 6 mth

-at 6 yrs →28% in 6wk & 2% in 6 mth

-at 10 yrs →no sig: difference(31% & 27%)

(5)comparing 3m & 6m groups at 2 year

-12 to 16% in 3 mth group

-12 to 17% in 12 mth group This study →fatal & nonfatal failure of

resolution,extension or recurrence during & after Tx →8% in both

Regarding risk of major bleeding

Studies(1996,2000 & 2005) →death rate from major hge=0.5% in 3m

Meta-analysis(2005) →same for both long term & short term anticoagulation

This study →0% in 3m &2% in 6mth

Regarding mortality

1 yr mortality from DVT or PE

-previous trials →0 to 2.2%

-study in 1992 →1%

-studies in 1996 & 2000 →0.5%

-this study →0.7% Death from major haemorrhage(b/t 1990-2005)

-0.1 to 0.4% for 3 mth

-0.1% for 6 mth

Summary

3 mth anticoag= same benefits as 6 mth but lower incidence of hge during Tx

Tx beyond 6mth →not ↓ risk of recurrence after warfarin is stopped

1st episode VTE →at least 3 mth warfarin Distal VTE →6 wks is adequate Continuing reversible risk factor →beyond

3 to 6m until risk=no longer present

For continuing Tx indefinitely

Pts with very high risk of recurrence

-> 1 episode of unprovoked thrombus

-cancer & thrombosis

-high risk thrombophilia

-severe post thrombotic syndrome

-strong preference for minimising risk of recurrence by continuing anticoagulation

THANK YOU