Venous thromboembolism: idiopathic: indefinite anticoagulation reduced recurrent episodes.

Clinical bottom line (level 1b)

Patients with a first episode of idiopathic thromboembolism who received indefinite anticoagulation compared with anticoagulation for 3 months, were less likely to have a recurrent venous thromboembolism (NNT = 5 at 10 months) .
There was no clear difference in mortality, major bleeding or patients stopping their medication.

Kearon et al: New England Journal of Medicine 1999; 340 (12): 901-907

Expires October 2003

The study

Double-blinded concealed randomised trial with intention-to-treat
Setting: 14 acute hospitals, USA and Canada

162 patients (aged mean 59, 60% male) with a first episode of idiopathic venous thromboembolism (objectively diagnosed) who received oral anticoagulation for three months following an initial course of heparin or LMWH.

Excluded if

initially treated with non-licenced LMWH

fracture or plaster cast of lower limb within previous 3 months

hospitalisation with confinement to bed for 3 consecutive days or use of general anaesthesia within previous 3 months

known deficiency of antithrombin, protein C or protein S

cancer in previous 5 years

contraindication to long-term anticoagulation

required long-term therapy with NSAIDs, ticlopidine, sulfinpyrazone, dipyridamole or more than 160 mg asprin per day

familial bleeding diathesis

major psychiatric disorder

pregnant or could become pregnant

life-expectancy < than 2 years

considered non-compliant

geographic inaccessibility precluded follow-up

Note:

Patients were stratified for DVT or pulmonary embolism, and centre before randomisation.

Control Group: (n = 83, 83 analysed): placebo
Experimental Group: (n = 79, 79 analysed): warfarin indefinitely adjusted so INR 2.0 to 3.0

100% followed for 10 months
Outcome notes:

recurrent venous thromboembolism : DVT by compression ultrasound or venography; PE by ventilation-perfusion scanning followed by compression ultrasound, bilateral venography or pulmonary angiography if non-diagnostic

major bleeding : clinically overt and associated with a fall in Hb of at least 20 g/l, a need for transfusion of 2 or more units, retroperitoneal or intracranial, or required permanent discontinuation of the study drug

The evidence

Outcome	Time to outcome	CER	EER	RRR (95% CI)	ARR (95% CI)	NNT (95% CI)
recurrent venous thromboembolism	10 months	17 (20.5%)	1 (1.27%)	94% (55% to 99%)	19.2% (10.2% to 28.2%)	5 (4 to 10)
death	10 months	3 (3.61%)	1 (1.27%)	65% (-230% to 96%)	2.35% (-2.36% to 7.06%)	43 (NNT = 14 to infinity; NNH = 42 to infinity)
major bleeding	10 months	0 (0.0%)	3 (3.80%)	% (% to %)	-3.80% (-8.01% to 0.42%)	-26 (NNT = 240 to infinity; NNH = 12 to infinity)
discontinued medication	10 months	13 (15.7%)	14 (17.7%)	-13% (-125% to 43%)	-2.06% (-13.6% to 9.43%)	-49 (NNT = 11 to infinity; NNH = 7 to infinity)

Recurrent episodes included 11 DVT, 5 non-fatal PE and 1 fatal PE.

Comments

Ongoing studies are in progress to determine if two years of anticoagulant therapy is sufficient, or if a lower intensity of anticoagulation (i.e., target International Normalized Ratio [INR]: 1.5 to 1.9) is effective after an initial 3 to 6 month period of higher-intensity anticoagulation (i.e., INR: 2.0 to 3.0).

Citation

Kearon C, Gent M, Hirsch J, et al: a comparison of three months of anticoagulation with extended anticoagulation for a first episode of idiopathic venous thromboembolism. New England Journal of Medicine 1999; 340 (12): 901-907

Search Terms: ?
Contributor: Chris Ball and Clare Wotton, October 1999
Reviewer: James Douketis

_{Clinical Question.}

_Patient	_{idiopathic venous thromboembolism}
_{Intervention or Exposure}	_{indefinite anticoagulation}
_Comparison	_{anticoagulation for 3 months}
_Outcome	_{recurrent venous thromboembolism, death, major bleeding}