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Meta-Analysis
. 2016 Nov 10;11(11):CD002783.
doi: 10.1002/14651858.CD002783.pub4.

Thrombolysis for acute deep vein thrombosis

Lorna Watson  1 , Cathryn Broderick, Matthew P Armon
Affiliations
Meta-Analysis

Thrombolysis for acute deep vein thrombosis

Lorna Watson et al. Cochrane Database Syst Rev. .

Update in

Abstract

Background: Standard treatment for deep vein thrombosis aims to reduce immediate complications. Use of thrombolysis or clot dissolving drugs could reduce the long-term complications of post-thrombotic syndrome (PTS) including pain, swelling, skin discolouration, or venous ulceration in the affected leg. This is the third update of a review first published in 2004.

Objectives: To assess the effects of thrombolytic therapy and anticoagulation compared to anticoagulation alone for the management of people with acute deep vein thrombosis (DVT) of the lower limb as determined by the effects on pulmonary embolism, recurrent venous thromboembolism, major bleeding, post-thrombotic complications, venous patency and venous function.

Search methods: For this update the Cochrane Vascular Information Specialist (CIS) searched the Specialised Register (February 2016). In addition the CIS searched the Cochrane Register of Studies (CENTRAL (2016, Issue 1)). Trial registries were searched for details of ongoing or unpublished studies.

Selection criteria: Randomised controlled trials (RCTs) examining thrombolysis and anticoagulation versus anticoagulation for acute DVT were considered.

Data collection and analysis: For this update (2016), LW and CB selected trials, extracted data independently, and sought advice from MPA where necessary. We assessed study quality with the Cochrane risk of bias tool. For dichotomous outcomes, we calculated the risk ratio (RR) and corresponding 95% confidence interval (CI). Data were pooled using a fixed-effect model unless significant heterogeneity was identified in which case a random-effects model was used. GRADE was used to assess the overall quality of the evidence supporting the outcomes assessed in this review.

Main results: Seventeen RCTs with 1103 participants were included. These studies differed in the both thrombolytic agent used and in the technique used to deliver it. Systemic, loco-regional and catheter-directed thrombolysis (CDT) were all included. Fourteen studies were rated as low risk of bias and three studies were rated as high risk of bias. We combined the results as any (all) thrombolysis compared to standard anticoagulation. Complete clot lysis occurred significantly more often in the treatment group at early follow-up (RR 4.91; 95% CI 1.66 to 14.53, P = 0.004) and at intermediate follow-up (RR 2.44; 95% CI 1.40 to 4.27, P = 0.002; moderate quality evidence). A similar effect was seen for any degree of improvement in venous patency. Up to five years after treatment significantly less PTS occurred in those receiving thrombolysis (RR 0.66, 95% CI 0.53 to 0.81; P < 0.0001; moderate quality evidence). This reduction in PTS was still observed at late follow-up (beyond five years), in two studies (RR 0.58, 95% CI 0.45 to 0.77; P < 0.0001; moderate quality evidence). Leg ulceration was reduced although the data were limited by small numbers (RR 0.87; 95% CI 0.16 to 4.73, P = 0.87). Those receiving thrombolysis had increased bleeding complications (RR 2.23; 95% CI 1.41 to 3.52, P = 0.0006; moderate quality evidence). Three strokes occurred in the treatment group, all in trials conducted pre-1990, and none in the control group. There was no significant effect on mortality detected at either early or intermediate follow-up. Data on the occurrence of pulmonary embolism (PE) and recurrent DVT were inconclusive. Systemic thrombolysis and CDT had similar levels of effectiveness. Studies of CDT included two trials in femoral and iliofemoral DVT, and results from these are consistent with those from trials of systemic thrombolysis in DVT at other levels of occlusion.

Authors' conclusions: Thrombolysis increases the patency of veins and reduces the incidence of PTS following proximal DVT by a third. Evidence suggests that systemic administration and CDT have similar effectiveness. Strict eligibility criteria appears to improve safety in recent studies and may be necessary to reduce the risk of bleeding complications. This may limit the applicability of this treatment. In those who are treated there is a small increased risk of bleeding. Using GRADE assessment, the evidence was judged to be of moderate quality due to many trials having low numbers of participants. However, the results across studies were consistent and we have reasonable confidence in these results.

PubMed Disclaimer

Conflict of interest statement

LW: has declared that she received travel and accomodation fees from the European Society of Angiology for speaking at the 2012 meeting on this topic CB: CB is a member of Cochrane Vascular's editorial base staff. Where appropriate, editorial tasks were carried out by other group members MPA: none known

Figures

1
1
Study flow diagram.
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1 Any thrombolysis versus control, Outcome 1 Any improvement in venous patency (early).
1.2
1.2. Analysis
Comparison 1 Any thrombolysis versus control, Outcome 2 Complete clot lysis (early).
1.3
1.3. Analysis
Comparison 1 Any thrombolysis versus control, Outcome 3 Bleeding (early).
1.4
1.4. Analysis
Comparison 1 Any thrombolysis versus control, Outcome 4 Stroke/intracerebral haemorrhage (early).
1.5
1.5. Analysis
Comparison 1 Any thrombolysis versus control, Outcome 5 Mortality (early).
1.6
1.6. Analysis
Comparison 1 Any thrombolysis versus control, Outcome 6 Pulmonary embolism (early).
1.7
1.7. Analysis
Comparison 1 Any thrombolysis versus control, Outcome 7 Post‐thrombotic syndrome (intermediate).
1.8
1.8. Analysis
Comparison 1 Any thrombolysis versus control, Outcome 8 Post‐thrombotic syndrome (late).
1.9
1.9. Analysis
Comparison 1 Any thrombolysis versus control, Outcome 9 Leg ulceration (intermediate).
1.10
1.10. Analysis
Comparison 1 Any thrombolysis versus control, Outcome 10 Leg ulceration (late).
1.11
1.11. Analysis
Comparison 1 Any thrombolysis versus control, Outcome 11 Complete clot lysis (intermediate).
1.12
1.12. Analysis
Comparison 1 Any thrombolysis versus control, Outcome 12 Complete clot lysis (late).
1.13
1.13. Analysis
Comparison 1 Any thrombolysis versus control, Outcome 13 Mortality (intermediate).
1.14
1.14. Analysis
Comparison 1 Any thrombolysis versus control, Outcome 14 Mortality (late).
1.15
1.15. Analysis
Comparison 1 Any thrombolysis versus control, Outcome 15 Normal venous function (intermediate).
1.16
1.16. Analysis
Comparison 1 Any thrombolysis versus control, Outcome 16 Recurrent DVT (intermediate).
2.1
2.1. Analysis
Comparison 2 Systemic thrombolysis versus control, Outcome 1 Any improvement in venous patency (early).
2.2
2.2. Analysis
Comparison 2 Systemic thrombolysis versus control, Outcome 2 Complete clot lysis (early).
2.3
2.3. Analysis
Comparison 2 Systemic thrombolysis versus control, Outcome 3 Bleeding (early).
2.4
2.4. Analysis
Comparison 2 Systemic thrombolysis versus control, Outcome 4 Stroke/intracerebral haemorrhage (early).
2.5
2.5. Analysis
Comparison 2 Systemic thrombolysis versus control, Outcome 5 Mortality (early).
2.6
2.6. Analysis
Comparison 2 Systemic thrombolysis versus control, Outcome 6 Pulmonary embolism (early).
2.7
2.7. Analysis
Comparison 2 Systemic thrombolysis versus control, Outcome 7 Post‐thrombotic syndrome (intermediate).
2.8
2.8. Analysis
Comparison 2 Systemic thrombolysis versus control, Outcome 8 Post‐thrombotic syndrome (late).
2.9
2.9. Analysis
Comparison 2 Systemic thrombolysis versus control, Outcome 9 Leg ulceration (intermediate).
2.10
2.10. Analysis
Comparison 2 Systemic thrombolysis versus control, Outcome 10 Leg ulceration (late).
2.11
2.11. Analysis
Comparison 2 Systemic thrombolysis versus control, Outcome 11 Complete clot lysis (intermediate).
2.12
2.12. Analysis
Comparison 2 Systemic thrombolysis versus control, Outcome 12 Complete clot lysis (late).
2.13
2.13. Analysis
Comparison 2 Systemic thrombolysis versus control, Outcome 13 Mortality (intermediate).
2.14
2.14. Analysis
Comparison 2 Systemic thrombolysis versus control, Outcome 14 Mortality (late).
2.15
2.15. Analysis
Comparison 2 Systemic thrombolysis versus control, Outcome 15 Normal venous function (intermediate).
2.16
2.16. Analysis
Comparison 2 Systemic thrombolysis versus control, Outcome 16 Recurrent DVT (late).
3.1
3.1. Analysis
Comparison 3 Loco‐regional thrombolysis versus control, Outcome 1 Complete clot lysis (early).
3.2
3.2. Analysis
Comparison 3 Loco‐regional thrombolysis versus control, Outcome 2 Bleeding (early).
3.3
3.3. Analysis
Comparison 3 Loco‐regional thrombolysis versus control, Outcome 3 Stroke/intracerebral haemorrhage (early).
3.4
3.4. Analysis
Comparison 3 Loco‐regional thrombolysis versus control, Outcome 4 Mortality (early).
3.5
3.5. Analysis
Comparison 3 Loco‐regional thrombolysis versus control, Outcome 5 Pulmonary embolism (early).
3.6
3.6. Analysis
Comparison 3 Loco‐regional thrombolysis versus control, Outcome 6 Post‐thrombotic syndrome (intermediate).
3.7
3.7. Analysis
Comparison 3 Loco‐regional thrombolysis versus control, Outcome 7 Leg ulceration (intermediate).
3.8
3.8. Analysis
Comparison 3 Loco‐regional thrombolysis versus control, Outcome 8 Complete clot lysis (intermediate).
3.9
3.9. Analysis
Comparison 3 Loco‐regional thrombolysis versus control, Outcome 9 Mortality (intermediate).
4.1
4.1. Analysis
Comparison 4 Catheter‐directed thrombolysis versus control, Outcome 1 Any improvement in venous patency (early).
4.2
4.2. Analysis
Comparison 4 Catheter‐directed thrombolysis versus control, Outcome 2 Complete clot lysis (early).
4.3
4.3. Analysis
Comparison 4 Catheter‐directed thrombolysis versus control, Outcome 3 Bleeding (early).
4.4
4.4. Analysis
Comparison 4 Catheter‐directed thrombolysis versus control, Outcome 4 Stroke/intracerebral haemorrhage (early).
4.5
4.5. Analysis
Comparison 4 Catheter‐directed thrombolysis versus control, Outcome 5 Mortality (early).
4.6
4.6. Analysis
Comparison 4 Catheter‐directed thrombolysis versus control, Outcome 6 Pulmonary embolism (early).
4.7
4.7. Analysis
Comparison 4 Catheter‐directed thrombolysis versus control, Outcome 7 Post‐thrombotic syndrome (intermediate).
4.8
4.8. Analysis
Comparison 4 Catheter‐directed thrombolysis versus control, Outcome 8 Post‐thrombotic syndrome (late).
4.9
4.9. Analysis
Comparison 4 Catheter‐directed thrombolysis versus control, Outcome 9 Leg ulceration (intermediate).
4.10
4.10. Analysis
Comparison 4 Catheter‐directed thrombolysis versus control, Outcome 10 Complete clot lysis (intermediate).
4.11
4.11. Analysis
Comparison 4 Catheter‐directed thrombolysis versus control, Outcome 11 Complete clot lysis (late).
4.12
4.12. Analysis
Comparison 4 Catheter‐directed thrombolysis versus control, Outcome 12 Normal venous function (intermediate).
4.13
4.13. Analysis
Comparison 4 Catheter‐directed thrombolysis versus control, Outcome 13 Recurrent VTE (intermediate).
4.14
4.14. Analysis
Comparison 4 Catheter‐directed thrombolysis versus control, Outcome 14 Recurrent VTE (late).
4.15
4.15. Analysis
Comparison 4 Catheter‐directed thrombolysis versus control, Outcome 15 Mortality (late).
See this image and copyright information in PMC

Update of

Comment in

References

References to studies included in this review

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Kiil 1981 {published data only}
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Marder 1977 {published data only}
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Schulman 1986 {published data only}
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Schweizer 1998 {published data only}
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Schweizer 2000 {published data only}
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Tsapogas 1973 {published data only}
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Turpie 1990 {published data only}
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Ugurlu 2002 {published data only}
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References to studies excluded from this review

Ansell 1990 {published data only}
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Bashir 2014 {published data only}
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Bieger 1976 {published data only}
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Browse 1968 {published data only}
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Cakir 2014 {published data only}
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Markevicius 2004 {published data only}
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Patra 2014 {published data only}
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Persson 1977 {published data only}
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Pinto 1997 {published data only}
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Robertson 1967 {published data only}
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References to ongoing studies

IRCT201108035625N3 {published data only}
    1. IRCT201108035625N3. Comparing the effect of conventional therapy (Heparin followed by warfarin) with interventional therapy (thrombolysis with or without angioplasty and stenting) on venous patency in patients who admitted with acute iliofemoral DVT in Tehran Heart Center Emergency Department. Iranian Registry of Clinical Trials (accessed 11 June 2015).
NCT00790335 {published data only}
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    1. Vedantham S, Goldhaber SZ, Kahn SR, Julian J, Magnuson E, Jaff MR, et al. Rationale and design of the ATTRACT Study: A multicenter randomized trial to evaluate pharmacomechanical catheter‐directed thrombolysis for the prevention of postthrombotic syndrome in patients with proximal deep vein thrombosis. American Heart Journal 2013;165(4):523‐30. - PMC - PubMed
NCT00970619 {published data only}
    1. DUTCH CAVA‐trial. Ultrasound accelerated catheter‐directed thrombolysis for primary iliofemoral deep vein thrombosis (IFDVT) compared to non‐invasive conventional anticoagulant therapy alone: a Dutch randomized controlled multicenter clinical trial. https://clinicaltrials.gov/ct2/show/NCT00970619 (accessed 11 June 2015).
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Additional references

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