Compression stockings for the prevention of post-thrombotic syndrome in patients with deep vein thrombosis – a systematic review

Protocol information Authors

Christopher F Berntsen1, Annette Kristiansen1, Elie A. Akl2, Per Olav Vandvik1

1Department of Internal Medicine, Sykehuset Innlandet Hospital Trust, Norway 2Department of Internal Medicine, American University of Beirut, Lebanon

Contact person

Christopher F Berntsen

Background The use of elastic compression stockings (ECS) in patients having experienced a deep vein thrombosis (DVT) has been common practice for years, with the rationale that they may prevent post-thrombotic syndrome (PTS), also known as post-phlebitic syndrome. It has been reported that 20-50% of DVT patients develop PTS, which consists in pain, feeling of heaviness, cramps or itching in the leg having been affected by the DVT (Bouman and Cate-Hoek 2014, Prandoni et al. 1997). Previous reports have indicated that the use of ECS may reduce the incidence of PTS (Brandjes et al. 1997, Prandoni et al. 2004), and a 2010 meta-analysis by Musani et al. (Musani et al. 2010) concluded that venous compression is likely to be effective, although they commented that more research on the subject was needed. Findings from a recently reported trial potentially contradict the usefulness of these stockings to prevent PTS (Kahn et al. 2013). Thus, we find it warranted to review the evidence available to guide recommendations on whether to include ECS as a part of standard care after DVT.

Description of the condition

Although there is no uniformly accepted definition of PTS (Ginsberg et al. 2001), it is generally described as a condition with symptoms ranging from swelling and edema of the lower extremity to outright ulcerations of the leg. Other symptoms include itching, ectatic veins, pain and paresthesias (Ginsberg et al. 2001, Kahn et al. 2013, Alatri et al. 2012, Bouman and Cate-Hoek 2014). Several scores have been developed to assess the severity of the condition, including the Ginsberg (Ginsberg et al. 2001) and Villalta (Prandoni et al. 1997) scales.

Description of the intervention

Compression stockings may be individually tailored, or off-the-rack (Kahn et al. 2013). They may be knee- or thigh high, and generally exert a pressure about 20-40 mmHg (Alatri et al. 2012).

How the intervention might work

Compression stockings have been postulated to improve venous return through external compression, thus reducing edema and swelling in the extremity and improving the microcirculation (Prandoni et al. 2004). Their use in PTS has been derived from their perceived usefulness in established primary venous insuffiency (Bouman and Cate-Hoek 2014).

file:///C:/Users/ChristopherFriis/Documents/RevMan/Compression%20stockings%20for%20the%20prevention%20of%20post-thrombotic%20syndrome%20in%20patients%20with%20deep%20vein%20thrombosis%20-%20060814-1134.htm%23REF-Bouman-and-Cate_x002d_Hoek-2014file:///C:/Users/ChristopherFriis/Documents/RevMan/Compression%20stockings%20for%20the%20prevention%20of%20post-thrombotic%20syndrome%20in%20patients%20with%20deep%20vein%20thrombosis%20-%20060814-1134.htm%23REF-Bouman-and-Cate_x002d_Hoek-2014file:///C:/Users/ChristopherFriis/Documents/RevMan/Compression%20stockings%20for%20the%20prevention%20of%20post-thrombotic%20syndrome%20in%20patients%20with%20deep%20vein%20thrombosis%20-%20060814-1134.htm%23REF-Prandoni-et-al.-1997file:///C:/Users/ChristopherFriis/Documents/RevMan/Compression%20stockings%20for%20the%20prevention%20of%20post-thrombotic%20syndrome%20in%20patients%20with%20deep%20vein%20thrombosis%20-%20060814-1134.htm%23REF-Brandjes-et-al.-1997file:///C:/Users/ChristopherFriis/Documents/RevMan/Compression%20stockings%20for%20the%20prevention%20of%20post-thrombotic%20syndrome%20in%20patients%20with%20deep%20vein%20thrombosis%20-%20060814-1134.htm%23REF-Prandoni-et-al.-2004file:///C:/Users/ChristopherFriis/Documents/RevMan/Compression%20stockings%20for%20the%20prevention%20of%20post-thrombotic%20syndrome%20in%20patients%20with%20deep%20vein%20thrombosis%20-%20060814-1134.htm%23REF-Musani-et-al.-2010file:///C:/Users/ChristopherFriis/Documents/RevMan/Compression%20stockings%20for%20the%20prevention%20of%20post-thrombotic%20syndrome%20in%20patients%20with%20deep%20vein%20thrombosis%20-%20060814-1134.htm%23REF-Kahn-et-al.-2013file:///C:/Users/ChristopherFriis/Documents/RevMan/Compression%20stockings%20for%20the%20prevention%20of%20post-thrombotic%20syndrome%20in%20patients%20with%20deep%20vein%20thrombosis%20-%20060814-1134.htm%23REF-Ginsberg-et-al.-2001file:///C:/Users/ChristopherFriis/Documents/RevMan/Compression%20stockings%20for%20the%20prevention%20of%20post-thrombotic%20syndrome%20in%20patients%20with%20deep%20vein%20thrombosis%20-%20060814-1134.htm%23REF-Ginsberg-et-al.-2001file:///C:/Users/ChristopherFriis/Documents/RevMan/Compression%20stockings%20for%20the%20prevention%20of%20post-thrombotic%20syndrome%20in%20patients%20with%20deep%20vein%20thrombosis%20-%20060814-1134.htm%23REF-Kahn-et-al.-2013file:///C:/Users/ChristopherFriis/Documents/RevMan/Compression%20stockings%20for%20the%20prevention%20of%20post-thrombotic%20syndrome%20in%20patients%20with%20deep%20vein%20thrombosis%20-%20060814-1134.htm%23REF-Alatri-et-al.-2012file:///C:/Users/ChristopherFriis/Documents/RevMan/Compression%20stockings%20for%20the%20prevention%20of%20post-thrombotic%20syndrome%20in%20patients%20with%20deep%20vein%20thrombosis%20-%20060814-1134.htm%23REF-Alatri-et-al.-2012file:///C:/Users/ChristopherFriis/Documents/RevMan/Compression%20stockings%20for%20the%20prevention%20of%20post-thrombotic%20syndrome%20in%20patients%20with%20deep%20vein%20thrombosis%20-%20060814-1134.htm%23REF-Bouman-and-Cate_x002d_Hoek-2014file:///C:/Users/ChristopherFriis/Documents/RevMan/Compression%20stockings%20for%20the%20prevention%20of%20post-thrombotic%20syndrome%20in%20patients%20with%20deep%20vein%20thrombosis%20-%20060814-1134.htm%23REF-Ginsberg-et-al.-2001file:///C:/Users/ChristopherFriis/Documents/RevMan/Compression%20stockings%20for%20the%20prevention%20of%20post-thrombotic%20syndrome%20in%20patients%20with%20deep%20vein%20thrombosis%20-%20060814-1134.htm%23REF-Prandoni-et-al.-1997file:///C:/Users/ChristopherFriis/Documents/RevMan/Compression%20stockings%20for%20the%20prevention%20of%20post-thrombotic%20syndrome%20in%20patients%20with%20deep%20vein%20thrombosis%20-%20060814-1134.htm%23REF-Prandoni-et-al.-1997file:///C:/Users/ChristopherFriis/Documents/RevMan/Compression%20stockings%20for%20the%20prevention%20of%20post-thrombotic%20syndrome%20in%20patients%20with%20deep%20vein%20thrombosis%20-%20060814-1134.htm%23REF-Kahn-et-al.-2013file:///C:/Users/ChristopherFriis/Documents/RevMan/Compression%20stockings%20for%20the%20prevention%20of%20post-thrombotic%20syndrome%20in%20patients%20with%20deep%20vein%20thrombosis%20-%20060814-1134.htm%23REF-Alatri-et-al.-2012file:///C:/Users/ChristopherFriis/Documents/RevMan/Compression%20stockings%20for%20the%20prevention%20of%20post-thrombotic%20syndrome%20in%20patients%20with%20deep%20vein%20thrombosis%20-%20060814-1134.htm%23REF-Alatri-et-al.-2012file:///C:/Users/ChristopherFriis/Documents/RevMan/Compression%20stockings%20for%20the%20prevention%20of%20post-thrombotic%20syndrome%20in%20patients%20with%20deep%20vein%20thrombosis%20-%20060814-1134.htm%23REF-Prandoni-et-al.-2004file:///C:/Users/ChristopherFriis/Documents/RevMan/Compression%20stockings%20for%20the%20prevention%20of%20post-thrombotic%20syndrome%20in%20patients%20with%20deep%20vein%20thrombosis%20-%20060814-1134.htm%23REF-Bouman-and-Cate_x002d_Hoek-2014file:///C:/Users/ChristopherFriis/Documents/RevMan/Compression%20stockings%20for%20the%20prevention%20of%20post-thrombotic%20syndrome%20in%20patients%20with%20deep%20vein%20thrombosis%20-%20060814-1134.htm%23REF-Bouman-and-Cate_x002d_Hoek-2014

Why it is important to do this review

Although compression stockings have been reported to be generally well tolerated (Prandoni et al. 2004), they are cumbersome for the patient, and treatment periods last for years, constituting a significant burden of treatment for the patients. It is important to establish whether the effect of this treatment is of a magnitude justifying such a long-time treatment. A search of the PROSPERO database (03 July 2014) did not identify any review covering this topic currently in progress.

Objectives To assess the benefits and harms of using elastic compression stockings (ECS) aimed at the prevention of post-thrombotic syndrome (PTS) for patients having experienced a deep vein thrombosis (DVT).

Methods Criteria for considering studies for this review

Types of studies

We will include randomized controlled trials (RCTs), and will also allow studies with a quasi-randomized approach (i.e. based on birth date, order of enrolment into study etc.) in the review. Only clinical studies with humans subjects will be included, animal and in vitro studies will consequently be excluded. We will exclude observational studies.

Types of participants

We will include studies on patients having experienced a symptomatic deep vein thrombosis which has also been objectively diagnosed, either through ultrasonography, phlebography or another suitable radiographic modality. For the use of ECS as secondary profylaxis against PTS, we will include patients having received ECS within 3 months from the DVT occured, and also patients without PTS symptoms having received ECS treament later than this.

We construe patients with established post-thrombotic syndrome at the time of ECS treatment startup as a separate population. We define the latter population as those patients having received delayed treatment (> 3 months after the DVT) and having symptoms of post-thrombotic syndrome at the time of treatment initiation. We have made a pragmatic decision about these two separate populations as treatment start in RCTs identified in previous reviews varied significantly between immediately up to one year after the event (Musani et al. 2010). We will perform a separate review to evaluate the benefit and harms of ECS in patients with established PTS.

Types of interventions

We will include studies using graduated compression stockings, both knee- and thigh high.

Types of outcome measures

Primary outcomes

We will include only patient-important outcomes, including:

Symptom burden measured with a relevant validated clinical scale (Villalta, Ginsberg or other)

Clinically important adverse events attributable to stocking use, including itching and rashes.

We will not evaluate surrogate outcomes such as radiographically demonstrated vein impatency.

file:///C:/Users/ChristopherFriis/Documents/RevMan/Compression%20stockings%20for%20the%20prevention%20of%20post-thrombotic%20syndrome%20in%20patients%20with%20deep%20vein%20thrombosis%20-%20060814-1134.htm%23REF-Prandoni-et-al.-2004file:///C:/Users/ChristopherFriis/Documents/RevMan/Compression%20stockings%20for%20the%20prevention%20of%20post-thrombotic%20syndrome%20in%20patients%20with%20deep%20vein%20thrombosis%20-%20060814-1134.htm%23REF-Prandoni-et-al.-2004file:///C:/Users/ChristopherFriis/Documents/RevMan/Compression%20stockings%20for%20the%20prevention%20of%20post-thrombotic%20syndrome%20in%20patients%20with%20deep%20vein%20thrombosis%20-%20060814-1134.htm%23REF-Musani-et-al.-2010file:///C:/Users/ChristopherFriis/Documents/RevMan/Compression%20stockings%20for%20the%20prevention%20of%20post-thrombotic%20syndrome%20in%20patients%20with%20deep%20vein%20thrombosis%20-%20060814-1134.htm%23REF-Musani-et-al.-2010

Secondary outcomes

We will evaluate the following secondary outcomes:

Recurrent venous thrombosis in the follow-up period

Death

Search methods for identification of studies

Electronic searches

We will search PubMed, Ovid MEDLINE and Ovid EMBASE (including EMBASE Classic) and Cochrane CENTRAL for relevant primary studies. Due to the more liberal indexing policies of EMBASE and hence larger output of EMBASE searches, we will exclude MEDLINE indexed journals in the search returns from EMBASE as we will assume these have been covered by the PubMed and Ovid MEDLINE searches.

We will also search the Cochrane Database of Systematic Reviews, as well as CRD/York databases including DARE, NHS EED and HTA databases for previous reviews on the topic and examine the bibliographies of previous reviews in order to identify further references to primary studies.

We will perform searches using relevant population and intervention freetext synonyms and relevant controlled vocabulary applicable to the database in question. We will not restrict searches by date or language, nor by outcome. We will not apply any filter. The full search strategies for each database are provided in the appendix. The search strategies have been developed by the the author (CFB) and peer-reviewed by trained medical librarians. For feasibility reasons, liteature search and screening for the population of this review (i.e. a prophylactic setting) and a PTS treatment setting for a separate review will be done simultaneously, as we expect large overlap in the search outputs. This is reflected in the search strategy. If anything, the concurrent search for the two populations is expected to increase the sensitivity of the search.

Searching other resources

We will hand-search bibliographies of included studies for other relevant studies not retrieved through the electronic search. Systematic reviews identified in the electronic search and deemed relevant to this topic by the screeners will first be checked against the Epistemonikos database to identify the primary studies used for the review (Epistemonikos 2014). If the review is not registered in Epistemonikos, the bibliography will be hand-searched. We will also search clinicaltrials.gov for relevant studies currently in progress.

Data collection and analysis

Selection of studies

Search outputs will be pooled and deduplicated using EndNote X7 (Thomson Reuters 2014). In the first round of screening, obviously irrelevant records will be excluded after independent duplicate examination of title and abstract. We will examine full texts of citations judged as potentially eligible by at least one reviewer. In the second round of screening, we will include RCTs and controlled clinical trials (CCTs) using a quasi-randomized approached as described above for the review. Screening will be performed independently by two reviewers (CFB and AK) using the web-based screening tool Covidence (Covidence 2014). We will seek to resolve disagreement by discussion. In case of unresolved disagreement, whether to include the study will be arbitrated by a third reviewer (POV).

We will also screen the outputs from the Cochrane Database of Systematic Reviews and the CRD/York databases, although these are not likely to contain primary studies eligible for this

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review, but may potentially inform the retrieval of primary studies not identified by the initial electronic search through previously conducted reviews. These will also be screened in duplicate for relevancy to the review question, and the bibliographies of secondary literature deemed relevant will be examined as described above. As many of the hits from these databases are likely to return duplicate hits in PubMed, Ovid MEDLINE and Ovid EMBASE, we will pool returns from all databases to reduce the screening burden.

Data extraction and management

Two reviewers (CFB and AK) will extract data independently using standardized data extraction forms in Covidence. In case of unresolved disagreement on the data extraction, a third reviewer (POV) will be consulted to reach an agreement. We will analyze data using RevMan 5.3 for metaanalyses (Cochrane 2014) and the SPSS statistical package for additional statistical analyses if needed (IBM 2013). If the Covidence data extraction form may not be fully adapted to extract all data needed, some data may be recorded using separate data extraction forms in Excel (Microsoft 2013). The field descriptions for the extraction form is provided in the appendix. The form will be piloted and calibrated for a subset of the included studies before full-scale data extraction. We will contact authors for needed but unreported data.

Assessment of risk of bias in included studies

Risk of bias in the included studies will be assessed using the Cochrane collaboration's tool for assessing risk of bias. The risk of bias will be registered using the tool as provided in the Covidence web-based software. We will compute a funnel plot and examine it for small-study effects.

Measures of treatment effect

Where a cutoff value for whether PTS is present is provided, this will be analysed as a dicotomous outcome. If such a cutoff is not provided explicitely, for the generally used scores we will construe a score higher than the commonly used cutoffs (e.g. 5 for the Villalta score) as an event, and a risk ratio will be calculated for the intervention and non-intervention groups. Treatment effects for dichtomous outcomes will be analysed as relative risks. Studies that report a numerical assessment of the severity of PTS will be analysed for treatment effect using the standard mean difference (SMD) of the relevant scale as the unit of measurement.

Unit of analysis issues

Analyses will be performed using single primary studies as the unit of analysis.

Dealing with missing data

We will conduct a complete case analysis in the main meta-analysis. For assessing the impact of missing data across studies, we will conduct sensitivity analyses making progressively more stringent assumptions regarding loss to follow-up in intervention and control groups. The extent to which point estimates and confidence intervals (CIs) differ in these sensitivity analyses will determine whether we rate down for risk of bias.

Assessment of heterogeneity

We will assess heterogeneity through standard statistical methods, calculating a p value for χ2 and an I2 statistic. For the I2, we will consider the following: 0–40% may be unimportant heterogeneity, 30–60% moderate, 50–90% substantial and 75–100% considerable heterogeneity.

Assessment of reporting biases

We will compute a funnel plot and evaluate this visually to assess whether a publication bias is likely to be present in the material examined.

file:///C:/Users/ChristopherFriis/Documents/RevMan/Compression%20stockings%20for%20the%20prevention%20of%20post-thrombotic%20syndrome%20in%20patients%20with%20deep%20vein%20thrombosis%20-%20060814-1134.htm%23REF-Cochrane-2014file:///C:/Users/ChristopherFriis/Documents/RevMan/Compression%20stockings%20for%20the%20prevention%20of%20post-thrombotic%20syndrome%20in%20patients%20with%20deep%20vein%20thrombosis%20-%20060814-1134.htm%23REF-IBM-2013file:///C:/Users/ChristopherFriis/Documents/RevMan/Compression%20stockings%20for%20the%20prevention%20of%20post-thrombotic%20syndrome%20in%20patients%20with%20deep%20vein%20thrombosis%20-%20060814-1134.htm%23REF-Microsoft-2013

Data synthesis

For categorical data, we will calculate relative risks separately for each trial for the incidence of outcomes by treatment arm. We will then pool the results of the different trials using a random-effects model for meta-analysis.

For continuous data, we will calculate the standard mean difference separately for each trial. We will then pool the results of the different trials using a random-effects model for meta-analysis.

Subgroup analysis and investigation of heterogeneity

We will perform subgroup analyses for those patients having received ECS treatment in the acute phase after the DVT, and those having received the intervention after an initial delay. We have, pragmatically, defined this delay as up to one month, as a previous review identified several studies with treatment initiation within this timeframe, and a smaller number of studies starting between 6 months and one year after the event (Musani et al. 2010). We will also perform subgroup analyses for patients that were symptomatic (Villalta score > 5 or equivalent) at the time of the intervention start, and those that were asymptomatic. Where data are available, we will also perform subgroup analyses for proximal and distal localization of the DVT, respectively. We define a proximal DVT as a DVT in the popliteal vein or more proximal, as opposed to a distal DVT in the calf veins.

Data for the efficacy of ECS for preventing PTS are a priori expected to be heterogenous, as the studies by Brandjes et al. and Prandoni et al. (Brandjes et al. 1997, Prandoni et al. 2004) are known by the authors to present contrasting findings compared to the recent study by Kahn et al. (Kahn et al. 2013). The lack of adequate blinding in the former studies (patients receiving no treatment rather than a placebo comparator) is a source of potentially substantial bias in the results, as lack of allocation concealment has been shown to inflate the magnitude of the intervention effect (Schulz 1995). If heterogeneity between blinded and non-blinded studies is detected, we will therefore perform subgroup analyses for the studies using placebo and no treatment comparators separately, calculating a ratio of odds ratios (ROR) between the groups. If a sufficient amount of studies may be included in the metaanalysis (i.e. 10 or more), we will consider performing a meta-regression and estimate whether there is significant difference in the effect estimates of the blinded and non-blinded studies, also assessing the amount of heterogeneity possibly explained by the lack or presence of allocation concealment.

If appropriate considering the heterogeneity between blinded and non-blinded studies, we will perform a metaanalysis to calculate a pooled estimate of the treatment effects for the prespecified outcomes.

Sensitivity analysis

As described above, we will perform sensitivity analyses to assess the potential effect of missing data. We will also perform sensitivity analyses excluding studies at high risk of bias.

Acknowledgements We would like to thank Marte Ødegaard at the University Library of Oslo for peer-reviewing the search strategy.

References Alatri et al. 2012

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file:///C:/Users/ChristopherFriis/Documents/RevMan/Compression%20stockings%20for%20the%20prevention%20of%20post-thrombotic%20syndrome%20in%20patients%20with%20deep%20vein%20thrombosis%20-%20060814-1134.htm%23REF-Musani-et-al.-2010file:///C:/Users/ChristopherFriis/Documents/RevMan/Compression%20stockings%20for%20the%20prevention%20of%20post-thrombotic%20syndrome%20in%20patients%20with%20deep%20vein%20thrombosis%20-%20060814-1134.htm%23REF-Brandjes-et-al.-1997file:///C:/Users/ChristopherFriis/Documents/RevMan/Compression%20stockings%20for%20the%20prevention%20of%20post-thrombotic%20syndrome%20in%20patients%20with%20deep%20vein%20thrombosis%20-%20060814-1134.htm%23REF-Prandoni-et-al.-2004file:///C:/Users/ChristopherFriis/Documents/RevMan/Compression%20stockings%20for%20the%20prevention%20of%20post-thrombotic%20syndrome%20in%20patients%20with%20deep%20vein%20thrombosis%20-%20060814-1134.htm%23REF-Kahn-et-al.-2013file:///C:/Users/ChristopherFriis/Documents/RevMan/Compression%20stockings%20for%20the%20prevention%20of%20post-thrombotic%20syndrome%20in%20patients%20with%20deep%20vein%20thrombosis%20-%20060814-1134.htm%23REF-Schulz-1995

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Sources of support Internal sources

Sykehuset Innlandet Hospital Trust, Norway

The funds for this review were provided by Sykehuset Innlandet Hospital Trust as part of PhD and post-doc grants for the authors, respectively.

External sources

No sources of support provided

Appendices 1 PubMed search strategy

Line

number Search string

1 veno* thrombo*

2 DVT

3 deep vein thrombos*

4 VTE

5 thromboemboli*

6 tromboemboli*

7 postthrombo* syndrom*

8 post thrombo* syndrom*

9 posttrombo* syndrom*

10 post trombo* syndrom*

11 postphlebiti* syndrom*

12 post phlebiti* syndrom*

13 venous thrombosis[mh]

14 venous thromboembolism[mh]

15 postthrombotic syndrome[mh]

16 compression stocking*

17 compression therap*

18 ECS

19 elastic stocking*

20 compression garment*

21 stockings, compression[mh]

22 #1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10 OR #11 OR #12 OR #13 OR

#14 OR #15

23 #16 OR #17 OR #18 OR #19 OR #20 OR #21

24 #22 AND #23

2 Ovid MEDLINE search strategy

Line number Search string

1 veno* thrombo*.mp.

2 DVT.mp.

3 deep vein thrombos*.mp.

4 VTE.mp.

5 thromboemboli*.mp.

6 tromboemboli*.mp.

7 postthrombo* syndrom*.mp.

8 post-thrombo* syndrom*.mp.

9 posttrombo* syndrom*.mp.

10 post-trombo* syndrom*.mp.

11 postphlebiti* syndrom*.mp.

12 post-phlebiti* syndrom*.mp.

13 exp venous thrombosis/

14 exp venous thromboembolism/

15 exp postthrombotic syndrome/

16 compression stocking*.mp.

17 compression therap*.mp.

18 ECS.mp.

19 elastic stocking*.mp.

20 compression garment*.mp.

21 exp stockings, compression/

22 or/1-15

23 or/16-21

24 and/22-23

3 Ovid EMBASE search strategy

Line number Search string

1 veno* thrombo*.mp.

2 DVT.mp.

3 deep vein thrombos*.mp.

4 VTE.mp.

5 thromboemboli*.mp.

6 tromboemboli*.mp.

7 postthrombo* syndrom*.mp.

8 post-thrombo* syndrom*.mp.

9 posttrombo* syndrom*.mp.

10 post-trombo* syndrom*.mp.

11 postphlebiti* syndrom*.mp.

12 post-phlebiti* syndrom*.mp.

13 exp postthrombosis syndrome/

14 exp vein thrombosis/

15 compression stocking*.mp.

16 compression therap*.mp.

17 ECS.mp.

18 elastic stocking*.mp.

19 compression garment*.mp.

20 exp compression stocking/

21 exp compression therapy/

22 or/1-14

23 or/15-21

24 and/22-23

25 limit 24 to exclude medline journals

4 Cochrane Library search strategy

Line number Search string

1 veno* thrombo*

2 DVT

3 deep vein thrombos*

4 VTE

5 thromboemboli*

6 tromboemboli*

7 postthrombo* syndrom*

8 post-thrombo* syndrom*

9 posttrombo* syndrom*

10 post-trombo* syndrom*

11 postphlebiti* syndrom*

12 post-phlebiti* syndrom*

13 [mh "venous thrombosis"]

14 [mh "venous thromboembolism"]

15 [mh "postthrombotic syndrome"]

16 compression stocking*

17 compression therap*

18 ECS

19 elastic stocking*

20 compression garment*

21 [mh "stockings, compression"]

22 {OR #1-#15}

23 {OR #16-#21}

24 {AND #22-#23}

5 CRD/York databases search strategy

Line

number Search string

1 veno* thrombo*

2 DVT

3 deep vein thrombos*

4 VTE

5 thromboemboli*

6 tromboemboli*

7 postthrombo* syndrom*

8 post-thrombo* syndrom*

9 posttrombo* syndrom*

10 post-trombo* syndrom*

11 postphlebiti* syndrom*

12 post-phlebiti* syndrom*

13 MeSH DESCRIPTOR venous thrombosis EXPLODE ALL TREES

14 MeSH DESCRIPTOR venous thromboembolism EXPLODE ALL TREES

15 MeSH DESCRIPTOR postthrombotic syndrome EXPLODE ALL TREES

16 compression stocking*

17 compression therap*

18 ECS

19 elastic stocking*

20 compression garment*

21 MeSH DESCRIPTOR stockings, compression EXPLODE ALL TREES

22 #1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10 OR #11 OR #12 OR #13 OR

#14 OR #15

23 #16 OR #17 OR #18 OR #19 OR #20 OR #21

24 #22 AND #23

6 Data extraction form

Data extraction form

Publication name (i.e. reference):

Author completing this form:

Date of completion of form:

Notes:

Details of study

Aim of intervention:

Aim of study:

Study design:

Method of recruiment of participants:

Inclusion/exclusion criteria:

Informed consent obtained? YES/NO/UNCLEAR

Ethical approval YES/NO/UNCLEAR

Funding (source, amount)

Statistical methods applied

Appropriateness of statistical methods

Risk of bias: Please register in Covidence document

Participants

Description

Geographical location

Setting

Number of

eligible participants

excluded

refusing to take part

randomised to intervention

randomised to control

excluded post randomization

withdrawn

lost to follow-up

died

included in analysis

included for each outcome

Mean age (+ standard deviation)

Age range

Gender

Ethnicity

Stage of PTS at inclusion

Treatment

Details of intervention

Details of control

Details of co-interventions in all groups

Delivery of intervention (timing, frequency, duration)

Details of providers of intervention

Was the intervention delivered as intended?

Outcomes

Primary outcomes (as stated by authors)

Secondary outcomes (as stated by authors)

Validity of outcome measures

Methods of follow-up

Timing of outcome assessment

Adverse events

Notes

Contact with author? YES/NO

Power calculation? YES/NO

Translated from non-English, non-Norwegian language? YES/NO

Duplicate publication? YES/NO

Results Please register in data section of Covidence file