Deep vein thrombosis (DVT) and pulmonary embolism (PE) are key complications after stroke that can lead to substantial morbidity and mortality. Rates of venous thromboembolism (VTE) were high in the past but have fallen, refl ecting increased use of early rehydration, mobilisation, and aspirin. An additional intervention is the use of graduated compression stockings (GCS), the effi cacy of which, although shown for surgery, is unproven in stroke. In The Lancet today, Martin Dennis and colleagues present the results of the CLOTS 1 trial, the fi rst large assessment of the safety and effi cacy of thigh-length GCS in patients with recent stroke. The CLOTS 1 trial is vitally important for stroke care. 2518 patients were recruited from 64 centres in Australia, Italy, and the UK (in the latter case, benefi tting from the UK Stroke Research Network) within 3 days of admission after stroke, and were representative of patients entering stroke services. The primary outcome was symptomatic or asymptomatic DVT detected on compression Doppler ultrasound, or symptomatic DVT, in the popliteal or femoral veins occurring within 30 days of randomisation. The trial found that GCS did not reduce DVT, compared with no GCS (absolute reduction 0·5%, 95% CI –1·9% to 2·9%, number needed to treat 200). GCS did not aff ect key secondary outcomes, including components of the primary outcome, as well as PE, VTE, and death. Importantly, GCS did not seem to be benefi cial in prespecifi ed subgroups: patients treated early, those with leg weakness, and those not given concomitant anticoagulation. Equally importantly, the use of GCS was associated with a fourfold increase in skin ulcers and necrosis, and a nonsignifi cant increase in lower-limb ischaemia. These results are supported by an earlier observational study that also found no benefi t with GCS. These fi ndings suggest that GCS do not work after stroke, although they do work after surgery. This might refl ect diff erences in the age of patients, duration of immobility, and comorbidities. Alternatively, CLOTS 1 could have obtained the wrong result. First, the trial might have been too small since it was only powered to detect a 4% absolute reduction in the primary outcome. However, the logistics and health economics of administering GCS to reduce DVT by, say, 2% are probably not worthwhile—for example, 24 stroke patients would need about 0·3 of a nurse per day just to measure and fi t GCS, with an additional cost per patient of about £20 for the stockings (assuming three pairs per patient). Second, the rate of proximal DVT (the type most likely to lead to PE) was lower than expected (10% vs 12%), which will have reduced the power of the study. Third, the trial was necessarily unblinded; however, the detection of DVT was made blinded to therapy by removing GCS with suffi cient time before ultrasound to allow skin indentations to disappear. Lack of treatment blinding could mean that investigators managed patients diff erently; the 0·8% excess use of anticoagulation in patients randomised to avoid GCS might indicate such a bias, although this is unlikely to have infl uenced the overall fi ndings. Fourth, although centres were trained in the sizing and fi tting of GCS, it is likely that both trial and clinical practice can result in the incorrect use of GCS; this practice would be ineff ective or even hazardous. Last, compliance is important and the CLOTS 1 investigators report that this was only 79% in the fi rst 14 days, and 73% up to 30 days. What then should be used for VTE prophylaxis after stroke? CLOTS 2 is a comparison of thigh-length versus below-knee GCS, but this trial will now close early in view of the CLOTS 1 results. Intermittent pneumatic compression has also been studied and CLOTS 3 is assessing this approach. Subcutaneous low-tomedium dose heparin is eff ective in reduction of VTE but unfortunately the reduction in PE, the primary
[1]
P. Bath,et al.
Low-molecular-weight heparins and heparinoids in acute ischemic stroke : a meta-analysis of randomized controlled trials.
,
2000,
Stroke.
[2]
Caroline Leigh Watkins.
The International Stroke Trial (IST): a randomised trial of aspirin, subcutaneous heparin, both, or neither among 19 435 patients with acute ischaemic stroke
,
1997
.
[3]
E. Oger,et al.
Prevention of venous thrombosis in patients with acute intracerebral hemorrhage
,
2005,
Neurology.
[4]
P. Sandercock,et al.
Physical Methods for Preventing Deep Vein Thrombosis in Stroke
,
2005,
The Cochrane database of systematic reviews.
[5]
J. Weinberger.
Tinzaparin in acute ischaemic stroke (TAIST): a randomised aspirin-controlled trial.
,
2003,
Current cardiology reports.
[6]
D. Leys,et al.
Compression stockings and the prevention of symptomatic venous thromboembolism: data from the Tinzaparin in Acute Ischemic Stroke Trial.
,
2005,
Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association.
[7]
P. Sandercock,et al.
Low-molecular-weight heparins or heparinoids versus standard unfractionated heparin for acute ischaemic stroke.
,
2017,
The Cochrane database of systematic reviews.
[8]
P. Langhorne.
Measures to Improve Recovery in the Acute Phase of Stroke
,
1999,
Cerebrovascular Diseases.
[9]
P. Sandercock,et al.
Effectiveness of thigh-length graduated compression stockings to reduce the risk of deep vein thrombosis after stroke (CLOTS trial 1): a multicentre, randomised controlled trial
,
2009,
The Lancet.
[10]
Catherine Sudlow,et al.
Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients
,
2002,
BMJ : British Medical Journal.
[11]
P. Sandercock,et al.
Low-molecular-weight heparins or heparinoids versus standard unfractionated heparin for acute ischaemic stroke.
,
2001,
The Cochrane database of systematic reviews.
[12]
A. Mattioli,et al.
Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients
,
2002,
BMJ : British Medical Journal.
[13]
P. Sandercock,et al.
Effectiveness of thigh-length graduated compression stockings to reduce the risk of deep vein thrombosis after stroke (CLOTS trial 1): a multicentre, randomised controlled trial
,
2009,
The Lancet.
[14]
Adnan I. Qureshi,et al.
Guidelines for the Early Management of Adults With Ischemic Stroke
,
2007
.
[15]
A. Sachdeva,et al.
Elastic compression stockings for prevention of deep vein thrombosis.
,
2000,
The Cochrane database of systematic reviews.
[16]
G. Agnelli,et al.
Prevention of venous thromboembolism after acute ischemic stroke
,
2005,
Journal of thrombosis and haemostasis : JTH.
[17]
A. Sachdeva,et al.
Elastic compression stockings for prevention of deep vein thrombosis.
,
2010,
The Cochrane database of systematic reviews.
[18]
Graeme J. Hankey.
Effectiveness of thigh-length graduated compression stockings to reduce the risk of deep vein thrombosis after stroke (CLOTS trial 1): a multicentre, randomised controlled trial
,
2009
.
[19]
Gary A. Ford,et al.
Guidelines for management of ischaemic stroke and transient ischaemic attack 2008.
,
2008,
Cerebrovascular diseases.
[20]
Peter Sandercock,et al.
The International Stroke Trial (IST): a randomised trial of aspirin, subcutaneous heparin, both, or neither among 19 435 patients with acute ischaemic stroke
,
1997,
The Lancet.