Influence of preceding length of anticoagulant treatment and initial presentation of venous thromboembolism on risk of recurrence after stopping treatment: analysis of individual participants’ data from seven trials

Boutitie and colleagues assess 7 pivotal trials to determine how the
length of anticoagulation and clinical presentation of venous
thromboembolism influences the risk of recurrence after anticoagulant
therapy is stopped[1]. In this assessment they classify patients in the
"traditional" manner as having distal deep vein thrombosis (DVT), proximal
DVT, or pulmonary embolism (PE) with or without DVT. They found that
those with isolated distal DVT had the lowest risk of recurrence compared
to proximal DVT or PE with or without DVT. Apart from a higher risk of
recurrence during the first 6 months after stopping treatment in
participants with PE who were treated only for 1.0 or 1.5 months
initially, there was no evidence that the location of the initial event
(proximal DVT or PE with or without DVT) altered the relative risk of
subsequent recurrence.

We have recently published an analysis of the reverse study that
shows that the type of initial presentation of idiopathic venous
thromboembolism (VTE) makes a difference[2]. We classified patients as
having proximal DVT only, PE only, or PE with DVT. All patients were
symptomatic, ie a patient with both PE and DVT had symptoms of each at
initial presentation and none were classified as PE and DVT based on a
finding of asymptomatic DVT on routine ultrasound of patients with
symptomatic PE.

With this classification we found that patients with initial
symptomatic idiopathic isolated PE had the lowest rate of recurrence after
anticoagulation was discontinued at the 6 month point. The crude
recurrent VTE rates for isolated PE, isolated DVT and PE with DVT groups
were 7.7 %, 16.5%, and 17.7% respectively. The relative risk of recurrent
VTE for isolated DVT versus isolated PE was 2.1 (95% confidence interval
1.2-3.7).

The reverse study data strongly suggests that patients with
idiopathic DVT with or without PE have the highest recurrence rate as
compared to patients with isolated PE. This likely has not been
demonstrated previously because traditionally patients are divided into PE
with or without DVT versus DVT only. There are a number of potential
reasons why patients with idiopathic DVT could have a higher recurrence
rate one of which is the recent demonstration that patients with DVT are
more likely to develop post thrombotic syndrome and that post thrombotic
signs and symptoms are important predictors of recurrent VTE[3].

References

1. Boutitie F, Pinede L, Schulman S, Agnelli G, Raskob G, Julian J,
et al. Influence of preceding length of anticoagulant treatment and
initial presentation of venous thromboembolism on risk of recurrence after
stopping treatment: analysis of individual participants' data from seven
trials. BMJ 2011;342:d3036.

2. Kovacs MJ, Kahn SR, Wells PS, Anderson DA, Chagnon I, Le Gal G, et
al. Patients with a first symptomatic unprovoked deep vein thrombosis are
at higher risk of recurrent venous thromboembolism than patients with a
first unprovoked pulmonary embolism. J Thromb Haemost. 2010; 8: 1926-32.

3. Rodger MA, Kahn SR, Wells PS, Anderson DA, Chagnon I, Le Gal G, et
al. Identifying unprovoked thromboembolism patients at low risk for
recurrence who can discontinue anticoagulant therapy. CMAJ. 2008 Aug
26;179(5):417-26.