Compression stockings in addition to low-molecular-weight heparin to prevent venous thromboembolism in surgical inpatients requiring pharmacoprophylaxis: the GAPS non-inferiority RCT
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Background
Patients admitted to hospital for surgery are at increased risk of venous thromboembolism (VTE). Pharmaco-thromboprophylaxis and mechanical prophylaxis (usually graduated compression stockings (GCS) or intermittent pneumatic compression) has been shown to reduce the incidence of VTE. The evidence base supporting The National Institute for Health and Care Excellence recommendation for the use of graduated compression stockings for VTE 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 (DVT) prevention in moderate and high risk elective surgical inpatients receiving low dose low-molecular-weight heparin (LMWH) pharmaco-thromboprophylaxis..
Objective(s)
The primary objective was to compare the VTE rate in elective surgical inpatients at moderate and high risk for VTE receiving either; graduated compression stockings and low dose low molecular weight heparin (standard care), or low dose low molecular weight heparin alone (intervention).
Design
A pragmatic, multicentre, prospective, non-inferiority, randomised controlled trial (RCT).
Setting
Secondary care National Health Service (NHS hospitals. in the UK
Participants
Patients aged ≥ 18 years, assessed as moderate or high risk of VTE according to the NHS England VTE Risk Assessment Tool (or the Trust equivalent based on this form), who were not contraindicated to LMWH or GCS were deemed eligible to take part.
Interventions
Participants were randomised 1:1 to either LMWH or LMWH and GCS.
Main outcome measures
The primary outcome measure was VTE up to 90 days after surgery. A combined endpoint of duplex ultrasound-proven new lower-limb DVT (symptomatic or asymptomatic) plus imaging confirmed symptomatic pulmonary embolism (PE). Secondary outcomes included, quality of life, compliance with GCS and LMWH during admission, and all-cause mortality.
Results
1905 participants underwent randomisation and 1858 were included in the intention-to-treat (ITT) analysis. A primary outcome event occurred in 16/937 (1.7%) patients in the LMWH alone arm compared to 13/921 (1.4%) in the LMWH plus GCS arm. The risk difference between LMWH and LMWH plus GCS was 0.30% (95% CI -0.65%, 1.26%). As the 95% confidence interval did not cross the non-inferiority margin of 3.5% (p-value <0.001 for non-inferiority), the results indicate that non-inferiority of LMWH alone was shown.
Limitations
13% of patients did not receive a duplex ultrasound scan which could have detected further asymptomatic DVT. However, missing scans were balanced between both study groups. The subgroup of those aged ≥65 years assessed as being at moderate VTE risk was underrepresented in the study, however this reflects that this group is underrepresented in the general population.
Conclusions
For elective surgical patients at moderate or high risk of VTE, administration of pharmaco-thromboprophylaxis alone is non-inferior to a combination of pharmaco-thromboprophylaxis and GCS. These findings indicate that GCS may be unnecessary for most elective surgical patients.
Future work
Further studies are needed to evaluate whether adjuvant GCS have a role in patients receiving extended thromboprophylaxis – beyond the period of hospital admission – following elective surgery, or in patients undergoing emergency surgical procedures.
Study registration:
This trial is registered as ISRCTN13911492.
Patients admitted to hospital for surgery are at increased risk of venous thromboembolism (VTE). Pharmaco-thromboprophylaxis and mechanical prophylaxis (usually graduated compression stockings (GCS) or intermittent pneumatic compression) has been shown to reduce the incidence of VTE. The evidence base supporting The National Institute for Health and Care Excellence recommendation for the use of graduated compression stockings for VTE 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 (DVT) prevention in moderate and high risk elective surgical inpatients receiving low dose low-molecular-weight heparin (LMWH) pharmaco-thromboprophylaxis..
Objective(s)
The primary objective was to compare the VTE rate in elective surgical inpatients at moderate and high risk for VTE receiving either; graduated compression stockings and low dose low molecular weight heparin (standard care), or low dose low molecular weight heparin alone (intervention).
Design
A pragmatic, multicentre, prospective, non-inferiority, randomised controlled trial (RCT).
Setting
Secondary care National Health Service (NHS hospitals. in the UK
Participants
Patients aged ≥ 18 years, assessed as moderate or high risk of VTE according to the NHS England VTE Risk Assessment Tool (or the Trust equivalent based on this form), who were not contraindicated to LMWH or GCS were deemed eligible to take part.
Interventions
Participants were randomised 1:1 to either LMWH or LMWH and GCS.
Main outcome measures
The primary outcome measure was VTE up to 90 days after surgery. A combined endpoint of duplex ultrasound-proven new lower-limb DVT (symptomatic or asymptomatic) plus imaging confirmed symptomatic pulmonary embolism (PE). Secondary outcomes included, quality of life, compliance with GCS and LMWH during admission, and all-cause mortality.
Results
1905 participants underwent randomisation and 1858 were included in the intention-to-treat (ITT) analysis. A primary outcome event occurred in 16/937 (1.7%) patients in the LMWH alone arm compared to 13/921 (1.4%) in the LMWH plus GCS arm. The risk difference between LMWH and LMWH plus GCS was 0.30% (95% CI -0.65%, 1.26%). As the 95% confidence interval did not cross the non-inferiority margin of 3.5% (p-value <0.001 for non-inferiority), the results indicate that non-inferiority of LMWH alone was shown.
Limitations
13% of patients did not receive a duplex ultrasound scan which could have detected further asymptomatic DVT. However, missing scans were balanced between both study groups. The subgroup of those aged ≥65 years assessed as being at moderate VTE risk was underrepresented in the study, however this reflects that this group is underrepresented in the general population.
Conclusions
For elective surgical patients at moderate or high risk of VTE, administration of pharmaco-thromboprophylaxis alone is non-inferior to a combination of pharmaco-thromboprophylaxis and GCS. These findings indicate that GCS may be unnecessary for most elective surgical patients.
Future work
Further studies are needed to evaluate whether adjuvant GCS have a role in patients receiving extended thromboprophylaxis – beyond the period of hospital admission – following elective surgery, or in patients undergoing emergency surgical procedures.
Study registration:
This trial is registered as ISRCTN13911492.
Date Issued
2020-12
Date Acceptance
2020-07-29
Citation
Health Technology Assessment, 2020, 24 (69), pp.1-117
ISSN
1366-5278
Publisher
NIHR Journals Library
Start Page
1
End Page
117
Journal / Book Title
Health Technology Assessment
Volume
24
Issue
69
Copyright Statement
© Queen’s Printer and Controller of HMSO 2020. This work was produced by Shalhoub et al. under the terms of a commissioning contract issued by the Secretary of State
for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in
professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial
reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House,
University of Southampton Science Park, Southampton SO16 7NS, UK.
for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in
professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial
reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House,
University of Southampton Science Park, Southampton SO16 7NS, UK.
License URL
Sponsor
National Institute for Health Research
Identifier
https://www.journalslibrary.nihr.ac.uk/hta/hta24690#/abstract
Grant Number
NIHR HTA Project Grant 14/140/61
Subjects
Venous Thromboembolism
Risk Assessment
Heparin, Low-Molecular-Weight
graduated compression stockings
surgery
non-inferiority
Publication Status
Published
Date Publish Online
2020-12