BACKGROUND: Patients admitted to hospital for surgery are at an increased risk of venous thromboembolism. Pharmaco-thromboprophylaxis and mechanical prophylaxis (usually graduated compression stockings or intermittent pneumatic compression) have been shown to reduce the incidence of venous thromboembolism. The evidence base supporting the National Institute for Health and Care Excellence's recommendation for the use of graduated compression stockings for venous thromboembolism prevention in the UK has recently been challenged. It is unclear if the risks and costs associated with graduated compression stockings are justified for deep-vein thrombosis prevention in moderate- and high-risk elective surgical inpatients receiving low-dose low-molecular-weight heparin pharmaco-thromboprophylaxis.
OBJECTIVES: The primary objective was to compare the venous thromboembolism rate in elective surgical inpatients at moderate or high risk of venous thromboembolism who were receiving either graduated compression stockings and low-dose low-molecular-weight heparin (standard care) or low-dose low-molecular-weight heparin alone (intervention).
DESIGN: This was a pragmatic, multicentre, prospective, non-inferiority, randomised controlled trial.
SETTING: This took place in secondary care NHS hospitals in the UK.
PARTICIPANTS: Patients aged ≥ 18 years who were assessed to be at moderate or high risk of venous thromboembolism according to the NHS England venous thromboembolism risk assessment tool (or the trust equivalent based on this form) and who were not contraindicated to low-molecular-weight heparin or graduated compression stockings were deemed eligible to take part.
INTERVENTIONS: Participants were randomised 1 : 1 to either low-molecular-weight heparin or low-molecular-weight heparin and graduated compression stockings.
MAIN OUTCOME MEASURES: The primary outcome measure was venous thromboembolism up to 90 days after surgery. A combined end point of duplex ultrasound-proven new lower-limb deep-vein thrombosis (symptomatic or asymptomatic) plus imaging-confirmed symptomatic pulmonary embolism. Secondary outcomes included quality of life, compliance with graduated compression stockings and low-molecular-weight heparin during admission, and all-cause mortality.
RESULTS: A total of 1905 participants were randomised and 1858 were included in the intention-to-treat analysis. A primary outcome event occurred in 16 out of 937 (1.7%) patients in the low-molecular-weight heparin-alone arm compared with 13 out of 921 (1.4%) patients in the low-molecular-weight heparin plus graduated compression stockings arm. The risk difference between low-molecular-weight heparin and low-molecular-weight heparin plus graduated compression stockings was 0.30% (95% confidence interval -0.65% to 1.26%). As the 95% confidence interval did not cross the non-inferiority margin of 3.5% (p < 0.001 for non-inferiority), the results indicate that non-inferiority of low-molecular-weight heparin alone was shown.
LIMITATIONS: In total, 13% of patients did not receive a duplex ultrasound scan that could have detected further asymptomatic deep-vein thrombosis. However, missing scans were balanced between both trial arms. The subpopulation of those aged ≥ 65 years assessed as being at a moderate risk of venous thromboembolism was under-represented in the study; however, this reflects that this group is under-represented in the general population.
CONCLUSIONS: For elective surgical patients at moderate or high risk of venous thromboembolism, administration of pharmaco-thromboprophylaxis alone is non-inferior to a combination of pharmaco-thromboprophylaxis and graduated compression stockings. These findings indicate that graduated compression stockings may be unnecessary for most elective surgical patients.
FUTURE WORK: Further studies are required to evaluate whether or not adjuvant graduated compression stockings have a role in patients receiving extended thromboprophylaxis, beyond the period of hospital admission, following elective surgery or in patients undergoing emergency surgical procedures.
TRIAL REGISTRATION: Current Controlled Trials ISRCTN13911492.
FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 69. See the NIHR Journals Library website for further project information.
|Number of pages||80|
|Journal||Health technology assessment (Winchester, England)|
|Publication status||Published - 1 Dec 2020|
This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 69. See the NIHR Journals Library website for further project information.
Trial Management Group
The Trial Management Group comprised Professor Alun Davies (as chief investigator), Ms Rebecca Lawton (as trial manager), Ms Jemma Hudson (as statistician) and Professor John Norrie (as senior statistician).
The Centre for Healthcare Randomised Trials
The following members were part of the wider CHaRT study team: Alison MacDonald (senior trial manager), Mr Mark Forrest (senior IT development manager) and Dr Samantha Wileman (quality assurance manager).
Department of Surgery and Cancer, Imperial College London
The following members were part of the wider GAPS trial team: Francine Heatley (trial manager), Becky Ward (sponsor), Matt Ryan (research manager), and Kirti Patel and Jayne Alderson (contracts).
Trial Steering Committee
We would like to thank Professor Robert Hinchliffe (chairperson, clinical professor of vascular surgery), Dr Peter MacCallum (senior lecturer in haematology), Mr Nick Hickey (consultant vascular surgeon)
and Dr Stephen Gerry (medical statistician and NIHR doctoral research fellow), and Ms Annya Stephens–Boal [lay member, Thrombosis UK (Llanwrda)], who provided invaluable input and advice as the independent lay member over the course of the study.
Data Monitoring Committee
The team would also like to thank the iDMC members, Mr Richard Bulbulia (chairperson, consultantvascular surgeon), Dr Adam Rye (consultant haematologist) and Professor Jonathan Emberson (associate professor, medical statistics and epidemiology) for their support and guidance.
Patient and public involvement
Annya Stephens–Boal was involved in the original design during the grant application stages and was an active member of the Trial Steering Committee throughout the study. Annya’s involvement is detailed in the patient and public involvement (PPI) lay person description (see Appendices 1 and 4).
Data cleaning was performed by the trial manager and study statistician.
- GRADUATED COMPRESSION STOCKINGS
- LOW-MOLECULAR-WEIGHT HEPARIN
- RISK ASSESSMENT
- VENOUS THROMBOEMBOLISM