Surgical inpatients are at an elevated risk of venous thromboembolism (VTE) when compared to medical inpatients and VTE prophylaxis has become a standard part of peri-operative care(1). A number of studies have cast doubt as to whether graduated compression stockings (GCS) confer any additional benefit when compared to pharmacological thromboprophylaxis alone(2-4). National guidelines recommend thromboprophylaxis with dual mechanical and pharmacological modalities for surgical inpatients but fail to specify whether mechanical measures refers to GCS or intermittent pneumatic compression in all but a few circumstances(5, 6). In light of new randomised trials that have been published in the interim, this updated systematic review and meta-analysis compares the effect of pharmacological prophylaxis and additional GCS versus pharmacological measures alone on the rate of venous thromboembolism (VTE), VTE-related mortality and adverse events for surgical inpatients.

The review was an update to a previously published peer-reviewed article and followed the previous protocol. The MEDLINE and Embase databases, the Cochrane Controlled Trials Register, Clinicaltrials.gov, European Union Clinical Trials, International Standard Randomised Controlled Trial Number and the Australian and New-Zealand Trials registries were searched up to December 2021. Randomised trials and trial arms reporting the rate of VTE after any surgical procedure utilising either pharmacological thromboprophylaxis alone or pharmacological thromboprophylaxis and additional GCS were included. The rate of deep venous thrombosis (DVT) was pooled in a meta-analysis with a fixed-effects model for head-to-head trials. Where data from trial arms were pooled, the rates of DVT, pulmonary embolism (PE), VTE-related mortality and adverse events were reported with a random effects model and meta-proportions analysis.

Two studies directly compared GCS and additional pharmacological prophylaxis to pharmacological prophylaxis alone. The risk of DVT in the GCS plus pharmacological prophylaxis group versus the pharmacological prophylaxis alone group was 0.67 (95% CI 0.41-1.10) (2 studies, 70 events, 2653 participants) (Figure 1). Heterogeneity as reported via I2 was 0%. The rate of DVT was reported in 31 studies and, for the GCS plus pharmacological prophylaxis group, the crude rate of DVT was 4.9% (26 studies, 99 events, 2205 participants) versus 9.5% (7 studies, 1129 events, 11,903 participants) for pharmacological prophylaxis alone. Pooling via meta-proportions was precluded in light significant statistical heterogeneity. In the GCS plus pharmacological prophylaxis group the pooled rate of PE was 0.05% (95% CI 0.00-0.30%) (2 studies, 1 event, 1316 participants, I2=40%) versus 0.07% (95% CI 0.01-0.17%) (2 studies, 2 events, 1336 participants, I2=38%) (see figure 5). The rate of PE across all studies with GCS plus pharmacological prophylaxis was 0.05% (95% CI 0.00-0.30%) (6 studies, 5 events, 1810 participants, I2=40%) versus 0.11 (95% CI 0.01-0.30%) (21 studies, 27 events, 9662 participants, I2=38%). There were 25 trials reporting on VTE-related mortality and there were no deaths in the GCS plus pharmacological prophylaxis group (5 studies, 0 events, 1184 participants). In the pharmacological prophylaxis alone arms the rate of VTE-related mortality was 0.03% (20 studies, 3 events, 9818 participants). Reported adverse events were minor and mostly skin irritations, abrasions or ulceration.

Evidence from head-to-head meta-analysis demonstrates non-inferiority of pharmacological prophylaxis alone when compared to pharmacological prophylaxis and additional GCS. Furthermore, GCS incur a significant cost to health services and cause discomfort for patients. The rates of DVT, PE and VTE-related mortality were not significantly different when data were pooled with meta-analysis, though there was a degree of statistical and clinical heterogeneity between the pooled trial arms.

1. Cohen AT, Agnelli G, Anderson FA, Arcelus JI, Bergqvist D, Brecht JG, et al. Venous thromboembolism (VTE) in Europe. The number of VTE events and associated morbidity and mortality. Thromb Haemost. 2007 Oct;98(4):756-64. 2. Dennis M, Sandercock PAG, Reid J, Graham C, Murray G, Venables G, 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. Lancet (London, England). 2009 Jun;373(9679):1958-65. 3. Mandavia R, Shalhoub J, Head K, Davies AH. The additional benefit of graduated compression stockings to pharmacologic thromboprophylaxis in the prevention of venous thromboembolism in surgical inpatients. J Vasc surgery Venous Lymphat Disord. 2015 Oct;3(4):447-455.e1. 4. Shalhoub J, Lawton R, Hudson J, Baker C, Bradbury A, Dhillon K, et al. Compression stockings in addition to low-molecular-weight heparin to prevent venous thromboembolism in surgical inpatients requiring pharmacoprophylaxis: the GAPS non-inferiority RCT. Health Technol Assess. 2020;24(69):1-80. 5. NICE. Venous thromboembolism in over 16s : reducing the risk of hospital-acquired deep vein thrombosis or pulmonary embolism. (March 2018). 6. Guyatt GH, Akl EA, Crowther M, Gutterman DD, Schuünemann HJ, Panel AC of CPAT and P of T. Executive summary: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest [Internet]. 2012 Feb;141(2 Suppl):7S-47S. Available from: https://pubmed.ncbi.nlm.nih.gov/22315257