Combined intermittent pneumatic leg compression and pharmacological prophylaxis for prevention of venous thromboembolism

Stavros Kakkos; George Kirkilesis; Joseph A Caprini; George Geroulakos; Andrew Nicolaides; Gerard Stansby; Daniel J Reddy

doi:10.1002/14651858.CD005258.pub4

Cochrane Database of Systematic Reviews

Compresión neumática intermitente de la pierna y profilaxis farmacológica combinadas para la profilaxis de la tromboembolia venosa en pacientes de alto riesgo

Información

DOI:

https://doi.org/10.1002/14651858.CD005258.pub4 Copiar DOI

Base de datos:

Cochrane Database of Systematic Reviews

Versión publicada:

28 enero 2022see what's new

Tipo:

Intervention

Etapa:

Review

Grupo Editorial Cochrane:

Grupo Cochrane de Vascular

Copyright:

Copyright © 2022 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Contraer

Autores

Stavros Kakkos

Correspondencia a: Department of Vascular Surgery, University of Patras Medical School, Patras, Greece

[email protected]
George Kirkilesis

Department of Vascular Surgery, University of Patras Medical School, Patras, Greece
Joseph A Caprini

NorthShore University HealthSystem, Evanston, USA

Pritzker School of Medicine, Chicago, USA
George Geroulakos

Department of Surgery and Cancer, Imperial College of Science Technology and Medicine, London, UK

Department of Vascular Surgery, Attikon University Hospital, National and Kapodistrian University, Athens, Greece
Andrew Nicolaides

Department of Surgery, University of Nicosia Medical School, Nicosia, Cyprus
Gerard Stansby

Northern Vascular Centre, Freeman Hospital, Newcastle, UK
Daniel J Reddy

Department of Surgery, Wayne State University, Detroit, USA

Contributions of authors

SK: selected studies, assessed study quality, extracted data, wrote the review
GK: selected studies, assessed study quality, extracted data, wrote the review
JC: arbitrated disagreements
GG: selected studies, assessed study quality, and extracted data
AN: contributed to the text of the review
GS: contributed to the text of the review
DR: contributed to the text of the review

Sources of support

Internal sources

No sources of support provided

External sources

Chief Scientist Office, Scottish Government Health Directorates, The Scottish Government, UK

The Cochrane Vascular editorial base is supported by the Chief Scientist Office.

Declarations of interest

SK: has declared that his institution received payment for the Victoria Study (Pfizer), and that he received consulting fees for participation in a panel of experts (Medtronic) and as part of a speakers bureau (LEO, Alfasigma, Viatris). SK has published editorials in Annals of Translational Medicine
GK: none known
JC: has declared that he received payments for lectures (Sanofi, Arjo), consultancy fees (Recovery Force)
GG: none known
AN: none known
GS: none known
DR: none known

Acknowledgements

The review authors wish to thank Dr Ntouvas for his contributions to the previous version. We also wish to thank Dr Arabi for providing additional unpublished results regarding fatal PE in the PREVENT study. We thank the Cochrane Vascular editorial base and editors for their input.

The review authors, and the Cochrane Vascular editorial base, are grateful to the following peer reviewers for their time and comments: Christos Stefanou, MD, PhD, EDIC, EDEC, Nicosia, Cyprus; Ankur Thapar, Consultant Vascular and Endovascular Surgeon, Mid and South Essex NHS Foundation Trust and Senior Lecturer, Anglia Ruskin University; Scott C Woller MD, Intermountain Medical Center, Intermountain Healthcare, USA; Dr Christopher Mathew, IMT (JRCPTB‐UK), Aster Wayanad, India.

Version history

Published

Title

Stage

Authors

Version

2022 Jan 28

Combined intermittent pneumatic leg compression and pharmacological prophylaxis for prevention of venous thromboembolism

Review

Stavros Kakkos, George Kirkilesis, Joseph A Caprini, George Geroulakos, Andrew Nicolaides, Gerard Stansby, Daniel J Reddy

https://doi.org/10.1002/14651858.CD005258.pub4

2016 Sep 07

Combined intermittent pneumatic leg compression and pharmacological prophylaxis for prevention of venous thromboembolism

Review

Stavros K Kakkos, Joseph A Caprini, George Geroulakos, Andrew N Nicolaides, Gerard Stansby, Daniel J Reddy, Ioannis Ntouvas

https://doi.org/10.1002/14651858.CD005258.pub3

2008 Oct 08

Combined intermittent pneumatic leg compression and pharmacological prophylaxis for prevention of venous thromboembolism in high‐risk patients

Review

Stavros K Kakkos, Joseph A Caprini, George Geroulakos, Andrew N Nicolaides, Gerard Stansby, Daniel J Reddy

https://doi.org/10.1002/14651858.CD005258.pub2

2005 Apr 20

Combined intermittent pneumatic leg compression and pharmacological prophylaxis for prevention of venous thromboembolism in high risk patients

Protocol

Stavros K Kakkos, George Geroulakos, Joseph A Caprini, Andrew N Nicolaides, Gerard P Stansby

https://doi.org/10.1002/14651858.CD005258

Differences between protocol and review

2021

We added the secondary outcome 'symptomatic DVT' as this was not considered appropriate to be described as a subgroup (as it was previously). We defined studies with a high or unclear risk of bias in any one or more domains as being at high risk overall. Given the high number of included studies at overall high risk of bias we were not able to carry out sensitivity analyses by risk of bias as previously planned. We clarified that we would investigate heterogeneity using subgroup analysis.

2016

The outcomes incidence of bleeding, incidence of major bleeding, and fatal bleeding are important adverse events of pharmacological prophylaxis and have been added to the review. The outcome fatal PE has been added to the review for completeness. The method of evaluating study quality has changed since the protocol was published; we used the Cochrane risk of bias (RoB 1) tool (Higgins 2011). We have also added summary of findings tables. Because risk stratification of study participants was not provided nor based on modern or any methodology, all types of participants were included and not only those considered as being at high risk of developing venous thromboembolism; however many studies included in this review included high‐risk patients such as those undergoing orthopaedic surgery.

Keywords

MeSH

Medical Subject Headings (MeSH) Keywords

Medical Subject Headings Check Words

Humans;

PICO

Population

Intervention

Comparison

Outcome

El uso y la enseñanza del modelo PICO están muy extendidos en el ámbito de la atención sanitaria basada en la evidencia para formular preguntas y estrategias de búsqueda y para caracterizar estudios o metanálisis clínicos. PICO son las siglas en inglés de cuatro posibles componentes de una pregunta de investigación: paciente, población o problema; intervención; comparación; desenlace (outcome).

Para saber más sobre el uso del modelo PICO, puede consultar el Manual Cochrane.

Figure 1

Study flow diagram

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Figure 2

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies

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Figure 3

Risk of bias summary: review authors' judgements about each risk of bias item for each included study

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Analysis 1.1

Comparison 1: IPC plus pharmacological prophylaxis versus IPC alone, Outcome 1: Incidence of PE ‐ orthopaedic and non‐orthopaedic patients

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Analysis 1.2

Comparison 1: IPC plus pharmacological prophylaxis versus IPC alone, Outcome 2: Incidence of PE ‐ foot IPC or other IPC

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Analysis 1.3

Comparison 1: IPC plus pharmacological prophylaxis versus IPC alone, Outcome 3: Incidence of DVT ‐ orthopaedic and non‐orthopaedic patients

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Analysis 1.4

Comparison 1: IPC plus pharmacological prophylaxis versus IPC alone, Outcome 4: Incidence of symptomatic DVT ‐ orthopaedic and non‐orthopaedic patients

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Analysis 1.5

Comparison 1: IPC plus pharmacological prophylaxis versus IPC alone, Outcome 5: Incidence of DVT ‐ by foot IPC or other IPC

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Analysis 1.6

Comparison 1: IPC plus pharmacological prophylaxis versus IPC alone, Outcome 6: Incidence of bleeding ‐ orthopaedic and non‐orthopaedic patients

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Analysis 1.7

Comparison 1: IPC plus pharmacological prophylaxis versus IPC alone, Outcome 7: Incidence of major bleeding ‐ orthopaedic and non‐orthopaedic patients

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Analysis 2.1

Comparison 2: IPC plus pharmacological prophylaxis versus pharmacological prophylaxis alone, Outcome 1: Incidence of PE ‐ orthopaedic and non‐orthopaedic patients

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Analysis 2.2

Comparison 2: IPC plus pharmacological prophylaxis versus pharmacological prophylaxis alone, Outcome 2: Incidence of PE ‐ foot IPC or other IPC

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Analysis 2.3

Comparison 2: IPC plus pharmacological prophylaxis versus pharmacological prophylaxis alone, Outcome 3: Incidence of DVT ‐ orthopaedic and non‐orthopaedic patients

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Analysis 2.4

Comparison 2: IPC plus pharmacological prophylaxis versus pharmacological prophylaxis alone, Outcome 4: Incidence of symptomatic DVT ‐ orthopaedic and non‐orthopaedic patients

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Analysis 2.5

Comparison 2: IPC plus pharmacological prophylaxis versus pharmacological prophylaxis alone, Outcome 5: Incidence of DVT ‐ foot IPC or other IPC

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Analysis 2.6

Comparison 2: IPC plus pharmacological prophylaxis versus pharmacological prophylaxis alone, Outcome 6: Incidence of bleeding ‐ orthopaedic and non‐orthopaedic patients

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Analysis 2.7

Comparison 2: IPC plus pharmacological prophylaxis versus pharmacological prophylaxis alone, Outcome 7: Incidence of major bleeding ‐ orthopaedic and non‐orthopaedic patients

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Analysis 3.1

Comparison 3: IPC plus pharmacological prophylaxis versus IPC plus aspirin, Outcome 1: Incidence of PE

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Analysis 3.2

Comparison 3: IPC plus pharmacological prophylaxis versus IPC plus aspirin, Outcome 2: Incidence of DVT

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Analysis 3.3

Comparison 3: IPC plus pharmacological prophylaxis versus IPC plus aspirin, Outcome 3: Incidence of symptomatic DVT

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Analysis 3.4

Comparison 3: IPC plus pharmacological prophylaxis versus IPC plus aspirin, Outcome 4: Incidence of bleeding

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Analysis 3.5

Comparison 3: IPC plus pharmacological prophylaxis versus IPC plus aspirin, Outcome 5: Incidence of major bleeding

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Analysis 4.1

Comparison 4: IPC plus pharmacological prophylaxis versus IPC alone ‐ RCTs only, Outcome 1: Incidence of PE

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Analysis 4.2

Comparison 4: IPC plus pharmacological prophylaxis versus IPC alone ‐ RCTs only, Outcome 2: Incidence of DVT

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Analysis 4.3

Comparison 4: IPC plus pharmacological prophylaxis versus IPC alone ‐ RCTs only, Outcome 3: Incidence of symptomatic DVT

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Analysis 4.4

Comparison 4: IPC plus pharmacological prophylaxis versus IPC alone ‐ RCTs only, Outcome 4: Incidence of DVT by foot IPC or other IPC

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Analysis 4.5

Comparison 4: IPC plus pharmacological prophylaxis versus IPC alone ‐ RCTs only, Outcome 5: Incidence of bleeding

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Analysis 4.6

Comparison 4: IPC plus pharmacological prophylaxis versus IPC alone ‐ RCTs only, Outcome 6: Incidence of major bleeding

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Analysis 5.1

Comparison 5: IPC plus pharmacological prophylaxis versus pharmacological prophylaxis alone ‐ RCTs only, Outcome 1: Incidence of PE

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Analysis 5.2

Comparison 5: IPC plus pharmacological prophylaxis versus pharmacological prophylaxis alone ‐ RCTs only, Outcome 2: Incidence of DVT

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Analysis 5.3

Comparison 5: IPC plus pharmacological prophylaxis versus pharmacological prophylaxis alone ‐ RCTs only, Outcome 3: Incidence of symptomatic DVT

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Analysis 5.4

Comparison 5: IPC plus pharmacological prophylaxis versus pharmacological prophylaxis alone ‐ RCTs only, Outcome 4: Incidence of DVT by foot IPC or other IPC

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Analysis 5.5

Comparison 5: IPC plus pharmacological prophylaxis versus pharmacological prophylaxis alone ‐ RCTs only, Outcome 5: Incidence of bleeding

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Analysis 5.6

Comparison 5: IPC plus pharmacological prophylaxis versus pharmacological prophylaxis alone ‐ RCTs only, Outcome 6: Incidence of major bleeding

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Analysis 6.1

Comparison 6: IPC plus pharmacological prophylaxis versus IPC plus aspirin ‐ RCTs only, Outcome 1: Incidence of PE

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Analysis 6.2

Comparison 6: IPC plus pharmacological prophylaxis versus IPC plus aspirin ‐ RCTs only, Outcome 2: Incidence of DVT

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Summary of findings 1. IPC plus pharmacological prophylaxis versus IPC alone

Outcomes	*Anticipated absolute effects ^ (95% CI)**		Relative effect (95% CI)	No of participants (studies)	Certainty of the evidence (GRADE)	Comments
Does combined intermittent pneumatic compression (IPC) plus pharmacological prophylaxis increase prevention of venous thromboembolism compared with IPC alone?
Patient or population: people undergoing surgery or at risk of developing VTE due to surgery, trauma or ICU stay Settings: hospital Intervention: combined modalities ‐ IPC plus pharmacological prophylaxis Comparison: IPC alone
Outcomes	Risk with IPC alone	Risk with combined modalities	Relative effect (95% CI)	No of participants (studies)	Certainty of the evidence (GRADE)	Comments
Incidence of PE^a (early postoperative period)	16 per 1000	7 per 1000 (4 to 12)	OR 0.51 (0.29 to 0.91)	5462 (19)	⊕⊕⊝⊝ Low^b
Incidence of DVT^c (early postoperative period)	38 per 1000	20 per 1000 (14 to 28)	OR 0.51 (0.36 to 0.72)	5394 (18)	⊕⊕⊝⊝ Low^b
Incidence of bleeding^d (early postoperative period)	10 per 1000	55 per 1000 (36 to 83)	OR 6.02 (3.88 to 9.35)	4634 (13)	⊕⊝⊝⊝ Very low^e
Incidence of major bleeding^f (early postoperative period)	3 per 1000	19 per 1000 (10 to 39)	OR 5.77 (2.81 to 11.83)	4133 (12)	⊕⊝⊝⊝ Very low^e
* The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI) CI: confidence interval;DVT: deep vein thrombosis;ICU: intensive care unit; IPC: intermittent pneumatic compression; OR: odds ratio; PE: pulmonary embolism; VTE: venous thromboembolism
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.
^aPulmonary embolism assessed by pulmonary angiography or scintigraphy, computed tomography (CT), angiography, or autopsy. ^bDowngraded by two levels due to risk of bias concerns (high in one or more domains regarding all but one study) and due to imprecision as a result of a small number of overall events. ^cDeep vein thrombosis assessed by ascending venography, I‐125 fibrinogen uptake test, and ultrasound scanning. ^d Any type of bleeding as described by the study authors. ^eDowngraded by three levels due to risk of bias concerns (high in one or more domains regarding all but one study), due to imprecision as a result of a small number of events overall, and indirectness because bleeding definitions were not uniform across the studies. ^fMajor bleeding as defined by the study authors, but usually located at the surgical site or in a critical organ or site, requiring intervention or transfusion of at least units of blood, or leading to death.

Summary of findings 1. IPC plus pharmacological prophylaxis versus IPC alone

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Summary of findings 2. IPC plus pharmacological prophylaxis versus pharmacological prophylaxis alone

Outcomes	*Anticipated absolute effects ^ (95% CI)**		Relative effect (95% CI)	No of participants (studies)	Certainty of the evidence (GRADE)	Comments
Does combined intermittent pneumatic compression (IPC) plus pharmacological prophylaxis increase prevention of venous thromboembolism compared with pharmacological prophylaxis alone?
Patient or population: people undergoing surgery or at risk of developing VTE because of surgery, trauma or ICU stay Settings: hospital Intervention: combined modalities ‐ IPC plus pharmacological prophylaxis Comparison: pharmacological prophylaxis alone
Outcomes	Risk with pharmacological prophylaxis alone	Risk with combined modalities	Relative effect (95% CI)	No of participants (studies)	Certainty of the evidence (GRADE)	Comments
Incidence of PE^a (early postoperative period)	18 per 1000	9 per 1000 (6 to 13)	OR 0.46 (0.30 to 0.71)	6737 (15)	⊕⊕⊝⊝ Low^b
Incidence of DVT^c (early postoperative period)	93 per 1000	37 per 1000 (21 to 67)	OR 0.38 (0.21 to 0.70)	6151 (17)	⊕⊕⊕⊕ High^d
Incidence of bleeding^e (early postoperative period)	74 per 1000	65 per 1000 (43 to 98)	OR 0.87 (0.56 to 1.35	1314 (6)	⊕⊝⊝⊝ Very low^f
Incidence of major bleeding^g (early postoperative period)	11 per 1000	13 per 1000 (4 to 44)	OR 1.21 (0.35 to 4.18)	908 (5)	⊕⊝⊝⊝ Very low^f
* The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI) CI: confidence interval;DVT: deep vein thrombosis;ICU: intensive care unit; IPC: intermittent pneumatic compression; OR: odds ratio; PE: pulmonary embolism; VTE: venous thromboembolism
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.
^aPulmonary embolism assessed by pulmonary angiography or scintigraphy, computed tomography (CT), angiography, single photon emission CT (SPECT) or autopsy. ^bDowngraded by two levels due to risk of bias (which was high in one or more domains regarding all studies) and due to imprecision as a result of a small number of events overall. ^cDeep vein thrombosis assessed predominantly by ascending venography, I‐125 fibrinogen uptake test, and ultrasound scanning. ^dDowngraded by one level due to risk of bias (which was high in one or more domains regarding all but one study) and upgraded by one level because of a large magnitude of the effect. ^eAny type of bleeding as described by the study authors. ^fDowngraded by three levels due to risk of bias (which was high in one or more domains regarding all studies), due to imprecision as a result of a small number of events overall and a wide confidence interval, and indirectness because bleeding definitions were not uniform across the studies. ^gMajor bleeding as defined by the study authors, but usually located at the surgical site or in a critical organ or site, requiring intervention or transfusion of at least units of blood, or leading to death.

Summary of findings 2. IPC plus pharmacological prophylaxis versus pharmacological prophylaxis alone

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Comparison 1. IPC plus pharmacological prophylaxis versus IPC alone

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1.1 Incidence of PE ‐ orthopaedic and non‐orthopaedic patients Show forest plot	19	5462	Odds Ratio (M‐H, Fixed, 95% CI)	0.51 [0.29, 0.91]

1.1.1 Orthopaedic patients	3	445	Odds Ratio (M‐H, Fixed, 95% CI)	Not estimable
1.1.2 Non‐orthopaedic patients	16	5017	Odds Ratio (M‐H, Fixed, 95% CI)	0.51 [0.29, 0.91]
1.2 Incidence of PE ‐ foot IPC or other IPC Show forest plot	19	5462	Odds Ratio (M‐H, Fixed, 95% CI)	0.51 [0.29, 0.91]

1.2.1 Foot IPC	1	50	Odds Ratio (M‐H, Fixed, 95% CI)	Not estimable
1.2.2 Other IPC	18	5412	Odds Ratio (M‐H, Fixed, 95% CI)	0.51 [0.29, 0.91]
1.3 Incidence of DVT ‐ orthopaedic and non‐orthopaedic patients Show forest plot	18	5394	Odds Ratio (M‐H, Fixed, 95% CI)	0.51 [0.36, 0.72]

1.3.1 Orthopaedic patients	3	445	Odds Ratio (M‐H, Fixed, 95% CI)	0.80 [0.38, 1.69]
1.3.2 Non‐orthopaedic patients	15	4949	Odds Ratio (M‐H, Fixed, 95% CI)	0.46 [0.31, 0.68]
1.4 Incidence of symptomatic DVT ‐ orthopaedic and non‐orthopaedic patients Show forest plot	10	4089	Odds Ratio (M‐H, Fixed, 95% CI)	0.48 [0.21, 1.10]

1.4.1 Orthopaedic patients	1	250	Odds Ratio (M‐H, Fixed, 95% CI)	1.50 [0.06, 37.33]
1.4.2 Non‐orthopaedic patients	9	3839	Odds Ratio (M‐H, Fixed, 95% CI)	0.44 [0.19, 1.04]
1.5 Incidence of DVT ‐ by foot IPC or other IPC Show forest plot	18	5395	Odds Ratio (M‐H, Fixed, 95% CI)	0.51 [0.36, 0.72]

1.5.1 Foot IPC	1	50	Odds Ratio (M‐H, Fixed, 95% CI)	Not estimable
1.5.2 Other IPC	17	5345	Odds Ratio (M‐H, Fixed, 95% CI)	0.51 [0.36, 0.72]
1.6 Incidence of bleeding ‐ orthopaedic and non‐orthopaedic patients Show forest plot	13	4634	Odds Ratio (M‐H, Fixed, 95% CI)	6.02 [3.88, 9.35]

1.6.1 Orthopaedic patients	2	400	Odds Ratio (M‐H, Fixed, 95% CI)	2.79 [0.77, 10.18]
1.6.2 Non‐orthopaedic patients	11	4234	Odds Ratio (M‐H, Fixed, 95% CI)	6.61 [4.14, 10.56]
1.7 Incidence of major bleeding ‐ orthopaedic and non‐orthopaedic patients Show forest plot	12	4133	Odds Ratio (M‐H, Fixed, 95% CI)	5.77 [2.81, 11.83]

1.7.1 Orthopaedic patients	2	400	Odds Ratio (M‐H, Fixed, 95% CI)	3.35 [0.13, 83.62]
1.7.2 Non‐orthopaedic patients	10	3733	Odds Ratio (M‐H, Fixed, 95% CI)	5.91 [2.83, 12.36]

Comparison 1. IPC plus pharmacological prophylaxis versus IPC alone

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Comparison 2. IPC plus pharmacological prophylaxis versus pharmacological prophylaxis alone

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
2.1 Incidence of PE ‐ orthopaedic and non‐orthopaedic patients Show forest plot	15	6737	Odds Ratio (M‐H, Fixed, 95% CI)	0.46 [0.30, 0.71]

2.1.1 Orthopaedic patients	8	1202	Odds Ratio (M‐H, Fixed, 95% CI)	0.58 [0.08, 4.49]
2.1.2 Non‐orthopaedic patients	7	5535	Odds Ratio (M‐H, Fixed, 95% CI)	0.46 [0.29, 0.71]
2.2 Incidence of PE ‐ foot IPC or other IPC Show forest plot	15	6737	Odds Ratio (M‐H, Fixed, 95% CI)	0.46 [0.30, 0.71]

2.2.1 Foot IPC	4	324	Odds Ratio (M‐H, Fixed, 95% CI)	0.32 [0.01, 8.25]
2.2.2 Other IPC	11	6413	Odds Ratio (M‐H, Fixed, 95% CI)	0.47 [0.30, 0.72]
2.3 Incidence of DVT ‐ orthopaedic and non‐orthopaedic patients Show forest plot	17	6151	Odds Ratio (M‐H, Random, 95% CI)	0.38 [0.21, 0.70]

2.3.1 Orthopaedic patients	10	3075	Odds Ratio (M‐H, Random, 95% CI)	0.34 [0.18, 0.68]
2.3.2 Non‐orthopaedic patients	7	3076	Odds Ratio (M‐H, Random, 95% CI)	0.46 [0.13, 1.61]
2.4 Incidence of symptomatic DVT ‐ orthopaedic and non‐orthopaedic patients Show forest plot	7	3032	Odds Ratio (M‐H, Fixed, 95% CI)	0.83 [0.34, 2.01]

2.4.1 Orthopaedic patients	3	477	Odds Ratio (M‐H, Fixed, 95% CI)	2.09 [0.38, 11.50]
2.4.2 Non‐orthopaedic patients	4	2555	Odds Ratio (M‐H, Fixed, 95% CI)	0.55 [0.18, 1.66]
2.5 Incidence of DVT ‐ foot IPC or other IPC Show forest plot	16	4148	Odds Ratio (M‐H, Random, 95% CI)	0.34 [0.18, 0.63]

2.5.1 Foot IPC	4	324	Odds Ratio (M‐H, Random, 95% CI)	0.40 [0.05, 3.47]
2.5.2 Other IPC	12	3824	Odds Ratio (M‐H, Random, 95% CI)	0.31 [0.17, 0.54]
2.6 Incidence of bleeding ‐ orthopaedic and non‐orthopaedic patients Show forest plot	6	1314	Odds Ratio (M‐H, Fixed, 95% CI)	0.87 [0.56, 1.35]

2.6.1 Orthopaedic patients	3	550	Odds Ratio (M‐H, Fixed, 95% CI)	0.64 [0.20, 2.07]
2.6.2 Non‐orthopaedic patients	3	764	Odds Ratio (M‐H, Fixed, 95% CI)	0.91 [0.57, 1.47]
2.7 Incidence of major bleeding ‐ orthopaedic and non‐orthopaedic patients Show forest plot	5	908	Odds Ratio (M‐H, Fixed, 95% CI)	1.21 [0.35, 4.18]

2.7.1 Orthopaedic patients	3	551	Odds Ratio (M‐H, Fixed, 95% CI)	1.07 [0.21, 5.54]
2.7.2 Non‐orthopaedic patients	2	357	Odds Ratio (M‐H, Fixed, 95% CI)	1.42 [0.21, 9.49]

Comparison 2. IPC plus pharmacological prophylaxis versus pharmacological prophylaxis alone

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Comparison 3. IPC plus pharmacological prophylaxis versus IPC plus aspirin

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
3.1 Incidence of PE Show forest plot	3	605	Odds Ratio (M‐H, Fixed, 95% CI)	0.33 [0.03, 3.19]

3.2 Incidence of DVT Show forest plot	3	605	Odds Ratio (M‐H, Fixed, 95% CI)	0.83 [0.48, 1.42]

3.3 Incidence of symptomatic DVT Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

3.4 Incidence of bleeding Show forest plot	3	616	Odds Ratio (M‐H, Fixed, 95% CI)	1.23 [0.27, 5.53]

3.5 Incidence of major bleeding Show forest plot	3	616	Odds Ratio (M‐H, Fixed, 95% CI)	0.80 [0.15, 4.17]

Comparison 3. IPC plus pharmacological prophylaxis versus IPC plus aspirin

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Comparison 4. IPC plus pharmacological prophylaxis versus IPC alone ‐ RCTs only

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
4.1 Incidence of PE Show forest plot	13	4159	Odds Ratio (M‐H, Fixed, 95% CI)	0.54 [0.28, 1.07]

4.2 Incidence of DVT Show forest plot	13	4159	Odds Ratio (M‐H, Fixed, 95% CI)	0.53 [0.36, 0.77]

4.3 Incidence of symptomatic DVT Show forest plot	7	3064	Odds Ratio (M‐H, Fixed, 95% CI)	1.21 [0.15, 9.63]

4.4 Incidence of DVT by foot IPC or other IPC Show forest plot	17	5085	Odds Ratio (M‐H, Fixed, 95% CI)	0.52 [0.36, 0.74]

4.4.1 Foot IPC	1	50	Odds Ratio (M‐H, Fixed, 95% CI)	Not estimable
4.4.2 Other IPC	16	5035	Odds Ratio (M‐H, Fixed, 95% CI)	0.52 [0.36, 0.74]
4.5 Incidence of bleeding Show forest plot	10	4120	Odds Ratio (M‐H, Fixed, 95% CI)	5.45 [3.38, 8.80]

4.6 Incidence of major bleeding Show forest plot	9	3619	Odds Ratio (M‐H, Fixed, 95% CI)	5.90 [2.82, 12.33]

Comparison 4. IPC plus pharmacological prophylaxis versus IPC alone ‐ RCTs only

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Comparison 5. IPC plus pharmacological prophylaxis versus pharmacological prophylaxis alone ‐ RCTs only

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
5.1 Incidence of PE Show forest plot	11	5758	Odds Ratio (M‐H, Fixed, 95% CI)	0.45 [0.29, 0.70]

5.2 Incidence of DVT Show forest plot	13	5172	Odds Ratio (M‐H, Random, 95% CI)	0.44 [0.22, 0.87]

5.3 Incidence of symptomatic DVT Show forest plot	5	2312	Odds Ratio (M‐H, Fixed, 95% CI)	1.02 [0.29, 3.54]

5.4 Incidence of DVT by foot IPC or other IPC Show forest plot	15	5431	Odds Ratio (M‐H, Random, 95% CI)	0.42 [0.23, 0.80]

5.4.1 Foot IPC	4	324	Odds Ratio (M‐H, Random, 95% CI)	0.40 [0.05, 3.47]
5.4.2 Other IPC	11	5107	Odds Ratio (M‐H, Random, 95% CI)	0.40 [0.20, 0.81]
5.5 Incidence of bleeding Show forest plot	4	594	Odds Ratio (M‐H, Fixed, 95% CI)	0.80 [0.30, 2.14]

5.6 Incidence of major bleeding Show forest plot	4	595	Odds Ratio (M‐H, Fixed, 95% CI)	1.21 [0.35, 4.18]

Comparison 5. IPC plus pharmacological prophylaxis versus pharmacological prophylaxis alone ‐ RCTs only

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Comparison 6. IPC plus pharmacological prophylaxis versus IPC plus aspirin ‐ RCTs only

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
6.1 Incidence of PE Show forest plot	2	405	Odds Ratio (M‐H, Fixed, 95% CI)	0.33 [0.03, 3.19]

6.2 Incidence of DVT Show forest plot	2	405	Odds Ratio (M‐H, Fixed, 95% CI)	0.79 [0.44, 1.39]

Comparison 6. IPC plus pharmacological prophylaxis versus IPC plus aspirin ‐ RCTs only

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Compresión neumática intermitente de la pierna y profilaxis farmacológica combinadas para la profilaxis de la tromboembolia venosa en pacientes de alto riesgo

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