Compression Therapy in Acute Deep Venous Thrombosis of the Lower Limb and for the Prevention of Post-Thrombotic Syndrome

A Review Based on a Structured Literature Search

Background: After an acute deep venous thrombosis (DVT) of the lower limb, 20% to 63% of patients develop post-thrombotic syndrome (PTS). In this review, we address the efficacy of compression therapy in the treatment of acute DVT of the lower limb, and for the prevention of PTS.

Methods: 12 randomized controlled trials (RCTs) and one meta-analysis, with a total of 3751 patients, were identified in a structured literature search.

Results: Two RCTs showed that adding compression therapy to drug treatment in the first 9 days of the acute phase of lower limb DVT led to more rapid pain relief (p<0.050) and less swelling (remaining difference in circumference, 1 cm versus 3 cm, p<0.050). As for the prevention of PTS, four RCTs showed a short-term benefit or no benefit of compression therapy. In three further RCTs, medical compression stockings (MCS) brought about a 16% to 27% absolute reduction of the frequency and severity of PTS (47% vs. 20 %, p<0.001; 40% vs. 21% (95% confidence intervals [29.9; 50.1] and [12.7; 29.5], respectively; and 58% vs. 42%, relative risk [RR] 0.73 [0,55; 0.96]). The benefit of MCS was also confirmed in a recent meta-analysis (RR 0.66 [0.44; 0.99], I2 = 88%). Thigh-length MCS were not superior to knee-length MCS for the prevention of PTS (33% vs. 36%, hazard ratio [HR] 0.93 [0.62; 1.41]). Individual, symptom-oriented tailoring of the duration of treatment was not inferior to a fixed treatment duration of 24 months (29% vs. 28%; odds ratio [OR] 1.06 [0.78;1.44]).

Conclusion: Compression therapy relieves symptoms in acute DVT and lessens the frequency and severity of PTS. It is therefore recommended as standard treatment.

Acute deep venous thrombosis (DVT) of the lower limb is characterized by an obstruction of the deep veins and muscular veins by thrombi, carrying the risk of potentially life-threatening embolization into the pulmonary circulation. Following proximal lower limb DVT, that is to say, affecting at least the popliteal vein, 20–63% of patients develop post-thrombotic syndrome (PTS), which, depending on the diagnostic criteria, causes a feeling of heaviness, a tendency to swelling, and pain. Patients may suffer different stages of chronic venous insufficiency (CVI) and even trophic disorders and ulceration. The Villalta score is used to establish the diagnosis and assess the severity of PTS (Table 1); this grades symptoms and clinical signs but does not record venous claudication (1, 2, 3, 4).

Table 1

Villalta score for the diagnosis and clinical assessment of the severity of post-thrombotic syndrome

The cause of the symptoms is venous stasis, which results either from delayed venous outflow due to persistent thrombi (occlusive type) or from post-thrombotic damage to venous valves and venous wall scarring (reflux type). Compression therapy counteracts venous hypertension and achieves a reduction in capillary leakage and edema. It improves the microcirculation of the skin and, by means of muscle compression, helps to reduce the diameter of the deep veins in the lower leg and support venous valve function (5).

Compression therapy can be carried out with phlebological compression bandages (PCB), medical compression stockings (MCS), or inelastic, medical adaptive compression systems and is simple and cost-effective to use. Moreover, in randomized controlled trials (RCTs), these treatment methods were able to reduce the risk of developing PTS by up to 50%. Therefore, guidelines recommended the wearing of MCS—with, however, a low level of recommendation in some cases (6, 7, 8). In 2014, the results of the SOX study (1) called compression therapy into question. Since then, there has been controversy regarding the benefits of compression therapy (9).

In consideration of the question of whether compression therapy improves symptoms in patients with acute lower limb DVT and reduces the risk of PTS, this review summarizes the currently available scientific data by means of a structured literature search and formulates recommendations for clinical routine on the basis of the current evidence.

Methods

For the review, the databases Medline, Embase, Web of Science, Cochrane Library, and the Regensburg Union Catalogue were searched by an independent person for the search terms: “compression treatment,” “compression stockings,” “compression hoisery,” “compression bandages,” “compression wraps,” AND “prevention of post-thrombotic syndrome.” The search was carried out for the period from 01.01.1990 and yielded 4384 hits (as of 24.08.2023). All hits were evaluated by two independent investigators with regard to study design and relevance according to pre-defined inclusion and exclusion criteria and using a quality standard checklist (power ≥ 80%, randomization, blinding, description of study dropouts, complete diagnostic work-up of the population, endpoint) (Figure 1) (10). From the remaining 132 publications, the 12 available RCTs and one meta-analysis including a total of 3751 patients and a follow-up period of 1–8 years were included in the review (Figure 2). All studies and recommendations were evaluated with regard to bias and evidence in accordance with the guidelines of the German Association of Scientific Medical Societies (Arbeitsgemeinschaft der Wissenschaftlichen Medizinische Fachgesellschaften e. V., AWMF) as well as using the levels of evidence as defined by the Oxford Centre for Evidence-Based Medicine (CEBM) (11) (12).

Figure 1

Quality characteristics of the RCTs included

Figure 2

Flow diagram of the literature search for the systematic review article

Results and discussion of the evidence

Table 2 provides a summary of the RCTs included. Indications and questions regarding compression therapy are considered separately below.

Table 2

Summary of the 12 RCTs included

Compression treatment in the acute phase of deep venous thrombosis of the lower limb

Partsch and Blättler first published a study in 2000 on the effect of treatment with thigh-length compression and mobilization on pain and leg swelling in acute proximal lower limb DVT compared to bed rest without compression. Each group of 15 patients was randomly assigned either to one of two intervention groups or to the control group. One intervention group received inelastic PCB in the form of a zinc paste bandage according to Fischer, while the other was treated with MCS in compression class (CCL) 2. Pain level and leg circumference both showed a significant reduction in the two intervention groups after 2 days, but not until after 9 days in the control group (pain: p < 0.050, swelling: p < 0.010) (13).

In the RCT conducted by Roumen-Klappe et al. in 2009, 34 lower limb DVT patients received a knee- or thigh-length PCB, depending on thrombus localization, as well as MCS once swelling had abated. The 35 lower limb DVT patients in the control group, on the other hand, were treated without compression therapy. After 7 days, the clinical symptoms of patients in the intervention group had significantly improved, including a reduction in leg swelling compared to the control group (a remaining 1-cm versus 3-cm difference in circumference compared to the healthy leg ; p < 0.050) (14).

Evaluation

Despite the small number of subjects, there are significant differences between the groups with and those without compression therapy in the acute phase of symptomatic lower limb DVT. A PCB effectively reduces pain and leg swelling and can be easily adjusted to the diminishing leg circumference in the further course. For practical reasons, PCB with short-stretch bandages is generally used, despite the fact that zinc paste bandages were used in the original literature. The primary use of MCS in acute lower limb DVT was investigated in only one of the studies analyzed, but also shows positive effects. However, in the case of relevant leg swelling, the MCS should not be fitted until after decongestion using a PCB.

Recommendation: In acute symptomatic lower limb DVT, compression therapy shall be initiated immediately following diagnosis, since this leads to a faster reduction in pain and swelling.

Compression treatment for the prevention of post-thrombotic syndrome

Once pain and leg swelling have subsided, the question arises as to whether continued compression therapy can prevent PTS. The occurrence of PTS following first-episode acute proximal lower limb DVT was investigated by Brandjes et al. in 1997 and by Prandoni et al. in 2004. In both studies, the 194 and 180 patients, respectively, were randomized following acute management to receive either 2 years of knee-length MCS or no compression. The primary endpoint was the cumulative incidence of PTS, which was determined using the Villalta score over a period of up to 5 years (15, 16). Significant differences were seen in the incidence of PTS, namely, 20% and 25%, respectively, in the intervention groups versus 47% and 49%, respectively, in the control groups. It was found that MCS reduced the risk of developing PTS by 51% (HR 0.49 [0.29; 0.84]).

In their 2008 study on 169 patients, Aschwanden et al. reported that after proximal lower limb DVT, 13% of study participants with knee-length MCS developed trophic disorders in the affected leg (stage C4–C6 in the CEAP classification), compared to 20% in the control group. The authors were able to show that the relative risk reduction of 65% in the 3-month follow-up period declined to 54% over the course of 1 year, after which no more differences could be seen (17).

In 2015, Jayaraj and Meissner found positive effects (lower point score in the Villalta and Venous Clinicial Severity scores) at 1 and 3 months for compression therapy with knee-length MCS compared to no compression in, admittedly, only 69 included patients. However, these positive effects could not be demonstrated at 6 and 12 months. Having said that, the dropout rate was over 50% (18).

In 2014, Kahn et al. published the results of the SOX study. A total of 803 patients with acute proximal lower limb DVT received knee-length MCS or placebo stockings with less than 5 mm Hg pressure. The stockings were first used on average 2 weeks following diagnosis and without instructions, since both types (MCS and placebo) were sent by post. Compliance was deemed to be good if the MCS were worn on at least 3 days a week. This went down to 55.6% during the 24-month follow-up period (1). No group difference with regard to PTS incidence could be seen, neither when using the Ginsberg criteria (19) nor when determining the Villalta score.

Yang et al. (Epub) published a monocentric RCT in 2021 on compression therapy in acute proximal lower limb DVT (20). A total of 113 patients received knee-length MCS, while the 119 patients in the control group did not. The incidence of PTS based on the Villalta score at 24 months was 42% with MCS versus 58% in the control group (RR 0.73 [0.55; 0.96]). Iliofemoral thrombosis was a risk factor for PTS compared to femoropopliteal thrombosis. On the other hand, high compliance for MCS had a protective effect.

Evaluation

Three of the cited studies showed a significant reduction in absolute PTS risk of 16–27% at 2 years with compression therapy. Two studies were able to demonstrate positive effects only in the short term, whereas the SOX study found no benefit for compression therapy. However, the latter study cannot be extrapolated to medical practice in Germany since the MCS therapy was not initiated until after a 2-week delay, despite the fact that early compression is crucial for treatment success and symptom resolution (13, 14). The study showed a very high PTS incidence of 52% in both groups (based on the Villalta score), which seems to be most likely explained by low self-reported adherence of participants, a lack of objectively assessed treatment adherence, the severity of PTS, as well as the fact that accuracy of fit of the stockings was not verified. Since it is questionable whether compression therapy can be properly used without instruction and monitoring, the study ultimately does not enable any robust conclusions to be drawn regarding the effectiveness of compression on the prevention of PTS (21).

The meta-analysis published in 2023 by Meng et al. (RR 0.66 [0.44; 0,99]; I² = 88%) (22) ) as well as a 2017 Cochrane review conducted by Appelen et al. (RR 0.62 [0.38; 1.01]) (23) come to the same conclusions as the authors of the present article and confirm the efficacy of knee-length compression therapy in PTS prevention. It should be noted that the heterogeneity of the two meta-analyses is caused only by the negative findings of the SOX study with completely contrasting results in comparison. If one had excluded this study, the relative risk reduction in the Cochrane review would have been 50% ([0.38; 0.66]; p < 0.00001) (23). Therefore, PCB or MCS correctly applied under supervision as well as targeted medical patient information regarding the reason for and duration of the treatment remain the cornerstones of PTS prevention.

Recommendation: Patients with acute symptomatic lower limb DVT shall receive custom-fitted MCS, since it has been shown that these reduce the risk of developing PTS by up to 50%.

Length and pressure of compression stockings for the prevention of PTS

For compliance reasons, the question often arises as to whether knee-length MCS are sufficient and which class of compression should be prescribed. In 2012, Prandoni et al. compared the use of thigh-length MCS with knee-length MCS for 2 years in 267 patients with first-episode lower limb DVT with regard to cumulative incidence of PTS over 3 years, based on Villalta score. Compliance for thigh-length MCS was 71% versus 83% for knee-length MCS. PTS developed in 33% of patients with thigh-length and in 36% of patients with knee-length MCS (HR 0.93 [0.62; 1.41]). Stocking-related discomfort occurred more frequently in patients with thigh-length MCS (41%) compared to knee-length MCS (27%) (p = 0.02) (24).

The CELEST trial, conducted by Galanaud et al. and published in 2022, investigated 341 patients and found that thigh-length MCS with an ankle pressure of 25 mm Hg are not inferior to MCS with an ankle pressure of 35 mm Hg in PTS prevention. PTS developed in 29% of the 25-mm-Hg group and in 35% of the 35-mm-Hg group (25).

Evaluation

The only RCT investigating different stocking lengths was unable to demonstrate any statistically significant benefit for thigh-length compared to knee-length MCS in the prevention of PTS. The positive trend found in favor of thigh-length stockings would only have become significant once approximately 8000 patients had been included (23). Therefore, stocking length should be selected according to the symptoms of congestion. Due to the more rapid resolution of symptoms (13, 14), the AWMF S2k guideline on venous thromboembolism that was updated in 2023 also recommends thigh-length MCS for patients with additional thigh swelling (21). This applies in particular in the case of pelvic vein thrombosis, which already increases the risk for the development of PTS (20).

MCS in CCL 2 with an ankle pressure of 23–32 mm Hg, which is sufficient for most patients, are those most commonly prescribed (25). In the case of patients with severe PTS, one can escalate to CCL 3 with an ankle pressure of 34–46 mm Hg or flat-knit MCS (15, 16, 20, 26, 27, 28).

Recommendation: Patients with acute symptomatic lower limb DVT shall receive compression therapy with knee-length MCS (A-D) in CCL 2, since these prevent the development of PTS equally well compared to thigh-length MCS. In the case of acute symptomatic lower limb DVT and (additional) thigh swelling, compression therapy with thigh-length MCS (A-G) should be performed at least initially, since these result in a more rapid resolution of clinical symptoms.

Duration of medical compression stocking use for the prevention of PTS

The OCTAVIA RCT conducted by Mol et al. in 2016 investigated 518 patients with proximal lower limb DVT to determine whether the use of knee-length MCS for only 12 months is non-inferior to 24-month therapy with regard to PTS development. PTS developed in 20% when MCS was discontinued after 12 months, compared to 13% after 24 months. Evidence of non-inferiority was narrowly missed; the number needed to treat to prevent the development of one case of PTS after a further 12 months of MCS therapy was 14 (29).

The IDEAL-DVT trial conducted by Ten Cate-Hoek et al. in 2018 included 864 patients without pre-existing CVI who had already received compression therapy for 6 months following acute lower limb DVT. Patients were randomized either to treatment with knee-length MCS to be individually shortened in the case of two consecutively determined Villalta Scores ≤ 4, or treatment was continued for the 24-month duration of the study. PTS occurred in 29% of patients with an individualized treatment duration and in 28% with the standard treatment duration (30). In their 2018 supplementary analysis of the IDEAL-DVT trial, Amin et al. demonstrated a positive effect for the individualized treatment duration on quality of life and cost savings (31).

Evaluation

In patients with acute symptomatic CVT, compression therapy with individualized treatment duration is not inferior to the standard treatment duration of 24 months in terms of the prevention of PTS, meaning that the former should be preferred (29, 30, 31). The decision-making process can include the following:

• An attempt at discontinuation over a few days
• Villalta score
• The results of digital photoplethysmography or venous occlusion plethysmography
• The results of venous duplex ultrasound with regard to deep venous insufficiency and residual thrombus burden (21).

The meta-analysis by Meng et al. in 2023 (22) also found no benefit for compression therapy carried out over 24 months compared to a treatment duration tailored to patients’ symptoms, limited to 6–12 months (RR 1.18 [0.75; 1.85]; I² = 76%).

Recommendation: In the case of acute symptomatic lower limb DVT, the indication to continue compression therapy beyond a duration of 6 months shall be reviewed on the basis of symptoms and clinical signs of chronic venous insufficiency. An individualized treatment duration should be favored over a fixed duration of 24 months.

Discussion and conclusions

The recommendation for compression therapy, which is to be initiated immediately upon diagnosis of lower limb DVT and carried out by professional staff, is based on the results of a number of RCTs and a recent meta-analysis. Despite overall small patient numbers, the lack of consistent blinding of study personnel, and the technical impracticability of blinding of patients, it can be concluded in summary that compression therapy has been shown to reduce not only swelling and pain in the acute phase of lower limb DVT but also the frequency and severity of PTS in the long term, as well as having a positive effect on the quality of life of those affected.

It is advisable to use PCB, preferably with short-stretch bandages (two-ply), as early on as possible in the acute phase if there is pronounced leg swelling and to fit MCS once leg swelling has subsided. If there is no or only slight venous congestion, knee-length MCS can also be used immediately. The respective recommendations can be found in the AWMF S2k guideline on the diagnosis and treatment of venous thrombosis and pulmonary embolism (21), which was updated in 2023, as well as in the guideline on medical compression therapy (8).

For the prevention of PTS, MCS are worn for an individually tailored duration, whereby treatment is guided by patients’ symptoms. Assuming there is no additional swelling of the thigh, the often better-tolerated knee-length MCS in CCL 2 are generally sufficient.

Conflict of interest statement

BL was coordinator of the 2023 AWMF S2k guideline on the diagnosis and treatment of venous thrombosis (Leitlinie zu Diagnostik und Therapie der Venenthrombose). She is Managing Director of the DGA (German Society for Angiology – Society for Vascular Medicine) and a member of the GTH (German Society for Thrombosis and Hemostasis Research).

BL was a co-author of the 2023 AWMF S2k guideline on the diagnosis and treatment of venous thrombosis.

TN received honoraria for consultancy activities from Medi Bayreuth and speaker’s fees from Sigvaris. He received support for travel expenses from Medi Bayreuth and Sigvaris.

The remaining authors declare that no conflict of interests exists.

Manuscript received on 23 October 2023, revised version accepted on 8 January 2024.

Translated from the original German by Christine Rye.

Corresponding author
Prof. Dr. rer. medic. Dorothea Thieme
Fakultät Angewandte Sozial- und Gesundheitswissenschaften
Ostbayrische Technische Hochschule Regensburg
Prüfeninger Straße 58
93053 Regensburg
Germany

Cite this as:
Thieme D, Linnemann B, Mühlberg K, Noppeney T, Kreutz M, Thieme M: Compression therapy in acute deep venous thrombosis of the lower limb and for the prevention of post-thrombotic syndrome—a review based on a structured literature search. Dtsch Arztebl Int 2024; 121: 188–94. DOI: 10.3238/arztebl.m2024.0001

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