B: Graduated compression stockings do not reduce the risk of post-stroke deep vein thrombosis
Submitting InstitutionUniversity of Edinburgh
Unit of AssessmentPsychology, Psychiatry and Neuroscience
Summary Impact TypeHealth
Research Subject Area(s)
Medical and Health Sciences: Cardiorespiratory Medicine and Haematology, Clinical Sciences, Neurosciences
Summary of the impact
Impact: Health and welfare: reducing morbidity; providing evidence
to disinvest in an ineffective
and damaging treatment; policy change.
Significance: Since 2009, applied clinical trial findings have
resulted in approximately 6000 fewer
complications (e.g., skin breaks) in the UK. Stocking use has decreased by
95%, which has saved
the NHS in excess of £20M per annum.
Beneficiaries: Stroke patients worldwide, the NHS and healthcare
delivery organisations, the
Attribution: Trials were designed and led by Professor M Dennis,
Reach: Changed national guidelines in at least seven countries
worldwide (Europe, N America,
South Africa, Singapore).
With £2.5M funding from the MRC, Chief Scientist Office and Chest, Heart
and Stroke Scotland,
Dennis (UoE 1990-present; now Professor of Stroke Medicine), Sandercock
now Professor of Medical Neurology), Murray (UoE 1996-present; Professor
of Medical Statistics),
and Reid (Consultant Radiologist, NHS; honorary UoE position) designed,
conducted and reported
the Clots in Legs Or sTockings after Stroke (CLOTS)-1 & -2 trials to
determine the role of
graduated compression stockings (GCS) for DVT prophylaxis after stroke.
These trials, which ran
concurrently 2001-2009, demonstrated GCS to be ineffective.
Over 130,000 people in the UK have a stroke each year and 25% of these
die within 6 months.
DVT, and resulting pulmonary emboli, is a major course of death.
Sandercock showed a) in 1999 [3.1] that, in stroke patients,
anticoagulants for DVT prophylaxis
had no net benefit and b) in 2002 [3.2] that there was no reliable
randomised trial evidence on the
effects of GCS in stroke. A systematic review commissioned by the Health
Group in 2005 showed that GCS and other physical methods of prophylaxis
were effective in
reducing DVT and pulmonary embolism in surgical patients. In 1999, a
survey of 1716 physicians
in the UK who managed stroke patients revealed that 46% thought GCS were
useful for prevention
of post-stroke DVT, 26% thought they were of no use and 28% were uncertain
of their value
(Ebrahim & Redfearn 1999). In Dennis's survey of 207 UK stroke units
(unpublished), 132 (89%) of
148 responders claimed to routinely use GCS, suggesting widespread use of
Given the cost in terms both of the stockings themselves and of the
nursing time involved in
applying them, there was a clear need for a randomised controlled trial to
establish the balance of
risk and benefit and to determine the cost-effectiveness of GCS.
The CLOTS-1 trial patients were randomised either to a policy of `routine
application of full-length
GCS' or to `avoid GCS' in the acute phase of stroke. The CLOTS-2 trial
patients were randomised
to `knee-length GCS' or to `full-length GCS'.
The results of CLOTS-1 were reported in 2009 [3.3]. In 2518 patients with
acute ischaemic stroke,
routine application of full-length GCS excluded a clinically significant
reduction in DVT or
pulmonary embolism, but was associated with a small but significant
(35/1000 patients treated)
excess of adverse effects (e.g., skin breaks). The publication of these
results led the CLOTS-2 trial
steering committee to close recruitment after 3114 patients had been
entered and followed up. The
results of the CLOTS-2 trial were published in 2010 [3.4]. This trial
showed that, among stroke
patients, those allocated knee-length GCS had a significantly higher risk
of DVT than those
allocated full-length GCS.
References to the research
3.1 Gubitz G, Counsell C, Sandercock P, Signorini D. Anticoagulants for
acute ischaemic stroke.
Cochrane Database Sys Rev. 2000;2:CD000024. DOI:
3.2 Mazzone C, Chiodo G, Sandercock P, Miccio M, Salvi R. Physical
methods for preventing
deep vein thrombosis in stroke. Cochrane Database Sys Rev.
3.3 Dennis M, Sandercock P, Reid J, et al. Effectiveness of thigh-length
stockings to reduce the risk of deep vein thrombosis after stroke (CLOTS
trial 1): a multicentre,
randomised controlled trial. Lancet. 2009;373:1958-65. DOI:
3.4 Dennis M, Sandercock P, Reid J, et al. Thigh-length versus below-knee
stockings for DVT
prophylaxis after stroke: a randomized trial. Ann Int Med.
2010;153:553-62. DOI: 10.7326/0003-4819-153-9-201011020-00280.
Details of the impact
CLOTS-1 showed that full-length GCS for stroke patients were ineffective,
and in fact had adverse
effects. CLOTS-2 indicated that knee-length GCS, which are more commonly
used, might actually
increase the risk of DVT.
Pathways to impact
The UoE trial team carried out a substantial programme of dissemination
activities beyond the
primary results publication: 20 local, national and international
conference presentations, two
webinars, materials posted on the CLOTS website
with five guideline committees (including the National Institute for
Health and Care Excellence
(NICE) and the Royal College of Physicians), and extensive media coverage.
These efforts have
directly impacted on both the revision of guidelines and on clinical
practice. The outcome has been
the diversion of valuable nursing time to other more effective areas of
stroke care than applying
and maintaining GCS compliance, ensuring greater comfort for patients by
them not having to wear
the stockings (which are hot, uncomfortable and often get soiled), and
substantial cost savings.
Impact on public policy
Prior to the publication of the results of CLOTS-1, the draft NICE
guidelines on the prevention of
venous thromboembolism in hospital patients recommended GCS in stroke
patients. However, the
final publication of the guidelines was delayed for 3 months so that the
results of the CLOTS-1 trial
could be taken into account. The final recommendation (March 2011) was:
"Do not offer anti-
embolism stockings for venous thromboembolism prophylaxis to patients who
are admitted for
The US guidelines now also recommend against routine use of GCS in stroke
patients [5.2]. The
American College of Physicians quoted the CLOTS trials and recommended
"against the use of
mechanical prophylaxis with graduated compression stockings for prevention
thromboembolism (grade: strong recommendation, moderate-quality evidence)"
in stroke patients
Also in response to the trial results, national guidelines in at least
Scotland [5.4], Singapore [5.5],
Canada [5.6], Italy and South Africa no longer recommend use of GCS in
Impact on practitioners and services
The trial results and resultant altered guidelines have had a clear effect
on healthcare provision in
the UK and beyond. The results of a 2011 web-based survey of practice
amongst UK stroke
physicians showed "the virtual eradication of use of stockings for
thromboprophylaxis in acute
stroke in the UK" and concluded that "the CLOTS studies have had a
dramatic impact on clinical
practice" [5.7]. These findings are supported by another study; "Data on
GCS use were available
for 1,971 patients with acute stroke enrolled into the Efficacy of Nitric
Oxide in Stroke trial from
February 2003 to April 2011. The use of GCS in the UK declined from 60.7%
(398/656) to 3.5%
(20/567) (p < 0.001) after publication of the CLOTS-1 trial
results. Similar reductions were seen in
other GCS-using countries. Practice change was apparent within 3 months of
Impact on the economy
The study findings are applicable to the approximately 65,000 immobile
stroke patients admitted to
hospital in the UK each year. Based on published figures [5.9], the
"virtual eradication" of GCS use
in the UK is estimated to have saved, per annum, £1.3M (assuming three
pairs/patient costing £7
each) for the GCS themselves, £20M in nursing time to size, fit and
monitor the stockings, plus
additional annual cost associated with the treatment of the 1500 patients
with skin breaks caused
by stocking use.
Impact on health and welfare
As a result of the CLOTS trials, stroke patients are no longer subjected
to wearing ineffective
uncomfortable stockings for prolonged periods in hospital. Furthermore,
they are at less risk of
developing skin damage/ulceration that may themselves prolong hospital
admission, estimated as
6000 fewer cases since 2009.
Sources to corroborate the impact
5.1 National Institute for Health and Care Excellence (2010 as amended).
thromboembolism: reducing the risk-full guideline. http://guidance.nice.org.uk/CG92.
5.2 Lansberg M, O'Donnell M, Khatri
P, et al.; American
College of Chest Physicians.
Antithrombotic and thrombolytic therapy for ischemic stroke:
antithrombotic therapy and prevention
of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based
2012; 141:e601S-36. DOI: 10.1378/chest.11-2302. [North American
5.3 Qaseem A, Chou C, Humphrey L, Starkey M, Shekelle P for the Clinical
Committee of the American College of Physicians. Venous thromboembolism
hospitalized patients: a clinical practice guideline from the American
College of Physicians. Ann
Intern Med. 2011;155:625-32. DOI: 10.7326/0003-4819-155-9-201111010-00011.
[Recommendations of the American College of Physicians.]
5.4 SIGN Guideline 118 (2010). Management of patients with stroke:
and management of complications, and discharge planning. http://www.sign.ac.uk/pdf/sign118.pdf
5.5 Venketasubramanian N, Pwee K, Chen C on behalf of the Singapore
Ministry of Health
Clinical Practice Guidelines Workgroup on Stroke and Transient Ischaemic
ministry of health clinical practice guidelines on stroke and transient
ischemic attacks. Int J Stroke.
2011;6:251-8. DOI: 10.1111/j.1747-4949.2011.00602.x. [Singaporean
5.6 Canadian Best Practice guidelines, fourth edition (2013).
5.7 Sett A, Mistri A. A dramatic impact of the CLOTS studies on clinical
practice in the UK. Int J
Stroke. 2011;6(suppl 2):15. DOI: 10.1111/j.1747-4949.2011.00684.x. [Corroborates
the impact of
CLOTS on UK clinical practice.]
5.8 Ankolekar S, Renton C, Bereczki D, et al. Effect of the neutral CLOTS
1 trial on the use of
graduated compression stockings in the Efficacy of Nitric Oxide Stroke
(ENOS) trial. J Neurol
Neurosurg Psychiatry. 2013;84:342-7. DOI: 10.1136/jnnp-2012-303396. [Corroborates
of CLOTS on clinical practice.]
5.9 Bath P, England T. Thigh-length compression stockings and DVT after
2009;373:1923-4. DOI: 10.1016/S0140-6736(09)60990-9. [Corroborates
cost savings in the UK.]