Anticoagulants (extended duration) for prevention of venous thromboembolism following total hip or knee replacement or hip fracture repair

Rachel Forster; Marlene Stewart

doi:10.1002/14651858.CD004179.pub2

Cochrane Database of Systematic Reviews

Anticoagulantes (de duración prolongada) para la prevención de la tromboembolia venosa posterior al reemplazo total de rodilla o cadera o la reparación de la fractura de cadera

Información

DOI:

https://doi.org/10.1002/14651858.CD004179.pub2 Copiar DOI

Base de datos:

Cochrane Database of Systematic Reviews

Versión publicada:

30 marzo 2016see what's new

Tipo:

Intervention

Etapa:

Review

Grupo Editorial Cochrane:

Grupo Cochrane de Vascular

Copyright:

Copyright © 2016 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Contraer

Autores

Rachel Forster

Correspondencia a: Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK

[email protected]

[email protected]
Marlene Stewart

Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK

Contributions of authors

RF and MS selected the studies, extracted the data, performed the statistical analyses and wrote the review.

Sources of support

Internal sources

No sources of support supplied

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.
National Institute for Health Research (NIHR), UK.

This project was supported by the NIHR, via Cochrane Incentive Award funding to Cochrane Vascular. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the Systematic Reviews Programme, NIHR, NHS or the Department of Health.

Declarations of interest

RF: none known.
MS: none known. MS is a member of Cochrane Vascular's editorial staff. To prevent any conflict of interest issues editorial decisions and activities related to this review were carried out by other editorial staff where appropriate.

Acknowledgements

The review authors thank Dr DJ Quinlan, Dr JW Eikelboom, and Dr JD Douketis for their work on the protocol of this review and Prof G Stansby and Dr R Hughes for their clinical input.

Version history

Published

Title

Stage

Authors

Version

2016 Mar 30

Anticoagulants (extended duration) for prevention of venous thromboembolism following total hip or knee replacement or hip fracture repair

Review

Rachel Forster, Marlene Stewart

https://doi.org/10.1002/14651858.CD004179.pub2

2002 Apr 22

Anticoagulants (extended duration) for prevention of venous thromboembolism following total hip or knee replacement or hip fracture repair

Protocol

Daniel John Quinlan, John W Eikelboom, James D Douketis

https://doi.org/10.1002/14651858.CD004179

Differences between protocol and review

New authors have taken over this review.

The outcome 'Total VTE' was added as several studies did not report VTE (specifically DVT) as symptomatic or asymptomatic, making it difficult to place within the previously listed outcome definitions. This way more data could be combined for comparison, but needed to be done with caution as the outcomes would be more heterogenous.

'Clinically relevant non‐major bleeding' was added to the bleeding outcomes as this was commonly reported in the newer, larger trials, and does not fit well within major or minor bleeding categories.

The outcomes 'Wound infection', 'Wound healing' and 'Reoperation following surgery' were added as they are deemed important outcomes for orthopaedic surgeons (Wang 2014).

Calculation of number needed to treat for an additional beneficial outcome (NNTB) and needed to treat for an additional harmful outcome (NNTH) were removed as the calculations in a meta‐analysis setting can be misleading and should be treated with caution.

The method of evaluating study quality has changed since the protocol was published; we used the Cochrane 'Risk of bias' tool (Higgins 2011). We have also added 'Summary of findings' tables.

In the 'Sensitivity analysis' section, we have removed the indication to compare results using a fixed and random‐effects model, as we are using the I² statistic to decide the appropriateness of the use of the different model types.

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 Heparin versus placebo, Outcome 1 Symptomatic VTE (DVT and PE).

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Analysis 1.2

Comparison 1 Heparin versus placebo, Outcome 2 Symptomatic DVT (proximal or distal).

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Analysis 1.3

Comparison 1 Heparin versus placebo, Outcome 3 Symptomatic PE.

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Analysis 1.4

Comparison 1 Heparin versus placebo, Outcome 4 Total VTE (symptomatic and asymptomatic).

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Analysis 1.5

Comparison 1 Heparin versus placebo, Outcome 5 Asymptomatic DVT.

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Analysis 1.6

Comparison 1 Heparin versus placebo, Outcome 6 All‐cause mortality.

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Analysis 1.7

Comparison 1 Heparin versus placebo, Outcome 7 Adverse events.

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Analysis 1.8

Comparison 1 Heparin versus placebo, Outcome 8 Bleeding ‐ major.

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Analysis 1.9

Comparison 1 Heparin versus placebo, Outcome 9 Bleeding ‐ minor.

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Analysis 1.10

Comparison 1 Heparin versus placebo, Outcome 10 Reoperation.

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Analysis 2.1

Comparison 2 Vitamin K antagonists versus placebo, Outcome 1 Symptomatic VTE (DVT and PE).

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Analysis 2.2

Comparison 2 Vitamin K antagonists versus placebo, Outcome 2 Symptomatic DVT (proximal or distal).

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Analysis 2.3

Comparison 2 Vitamin K antagonists versus placebo, Outcome 3 Symptomatic PE.

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Analysis 2.4

Comparison 2 Vitamin K antagonists versus placebo, Outcome 4 Total VTE (symptomatic and asymptomatic).

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Analysis 2.5

Comparison 2 Vitamin K antagonists versus placebo, Outcome 5 All‐cause mortality.

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Analysis 2.6

Comparison 2 Vitamin K antagonists versus placebo, Outcome 6 Adverse events.

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Analysis 2.7

Comparison 2 Vitamin K antagonists versus placebo, Outcome 7 Bleeding ‐ major.

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Analysis 3.1

Comparison 3 DOAC versus placebo, Outcome 1 Symptomatic VTE (DVT and PE).

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Analysis 3.2

Comparison 3 DOAC versus placebo, Outcome 2 Symptomatic DVT (proximal or distal).

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Analysis 3.3

Comparison 3 DOAC versus placebo, Outcome 3 Symptomatic PE.

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Analysis 3.4

Comparison 3 DOAC versus placebo, Outcome 4 Total VTE (symptomatic and asymptomatic).

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Analysis 3.5

Comparison 3 DOAC versus placebo, Outcome 5 All‐cause mortality.

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Analysis 3.6

Comparison 3 DOAC versus placebo, Outcome 6 Adverse events.

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Analysis 3.7

Comparison 3 DOAC versus placebo, Outcome 7 Bleeding ‐ major.

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Analysis 3.8

Comparison 3 DOAC versus placebo, Outcome 8 Bleeding‐ clinically relevant non‐major.

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Analysis 3.9

Comparison 3 DOAC versus placebo, Outcome 9 Bleeding ‐ minor.

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Analysis 3.10

Comparison 3 DOAC versus placebo, Outcome 10 Reoperation.

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Analysis 3.11

Comparison 3 DOAC versus placebo, Outcome 11 Wound infection.

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Analysis 4.1

Comparison 4 Anticoagulant (chosen at investigators' discretion) versus placebo, Outcome 1 Symptomatic VTE (DVT and PE).

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Analysis 4.2

Comparison 4 Anticoagulant (chosen at investigators' discretion) versus placebo, Outcome 2 Symptomatic DVT (proximal or distal).

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Analysis 4.3

Comparison 4 Anticoagulant (chosen at investigators' discretion) versus placebo, Outcome 3 Symptomatic PE.

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Analysis 4.4

Comparison 4 Anticoagulant (chosen at investigators' discretion) versus placebo, Outcome 4 Total VTE (symptomatic and asymptomatic).

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Analysis 4.5

Comparison 4 Anticoagulant (chosen at investigators' discretion) versus placebo, Outcome 5 Asymptomatic DVT.

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Analysis 4.6

Comparison 4 Anticoagulant (chosen at investigators' discretion) versus placebo, Outcome 6 Asymptomatic distal DVT.

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Analysis 4.7

Comparison 4 Anticoagulant (chosen at investigators' discretion) versus placebo, Outcome 7 All‐cause mortality.

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Analysis 4.8

Comparison 4 Anticoagulant (chosen at investigators' discretion) versus placebo, Outcome 8 Bleeding ‐ major.

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Analysis 5.1

Comparison 5 Vitamin K antagonists versus heparin, Outcome 1 Symptomatic VTE (DVT and PE).

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Analysis 5.2

Comparison 5 Vitamin K antagonists versus heparin, Outcome 2 Symptomatic DVT (proximal or distal).

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Analysis 5.3

Comparison 5 Vitamin K antagonists versus heparin, Outcome 3 Symptomatic PE.

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Analysis 5.4

Comparison 5 Vitamin K antagonists versus heparin, Outcome 4 Total VTE (symptomatic and asymptomatic).

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Analysis 5.5

Comparison 5 Vitamin K antagonists versus heparin, Outcome 5 All‐cause mortality.

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Analysis 5.6

Comparison 5 Vitamin K antagonists versus heparin, Outcome 6 Bleeding ‐ major.

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Analysis 5.7

Comparison 5 Vitamin K antagonists versus heparin, Outcome 7 Bleeding ‐ minor.

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Analysis 5.8

Comparison 5 Vitamin K antagonists versus heparin, Outcome 8 Reoperation.

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Analysis 6.1

Comparison 6 DOAC versus heparin, Outcome 1 Symptomatic VTE (DVT and PE).

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Analysis 6.2

Comparison 6 DOAC versus heparin, Outcome 2 Symptomatic DVT (proximal or distal).

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Analysis 6.3

Comparison 6 DOAC versus heparin, Outcome 3 Symptomatic PE.

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Analysis 6.4

Comparison 6 DOAC versus heparin, Outcome 4 Total VTE (symptomatic and asymptomatic).

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Analysis 6.5

Comparison 6 DOAC versus heparin, Outcome 5 Asymptomatic DVT.

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Analysis 6.6

Comparison 6 DOAC versus heparin, Outcome 6 Asymptomatic proximal DVT.

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Analysis 6.7

Comparison 6 DOAC versus heparin, Outcome 7 Asymptomatic distal DVT.

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Analysis 6.8

Comparison 6 DOAC versus heparin, Outcome 8 All‐cause mortality.

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Analysis 6.9

Comparison 6 DOAC versus heparin, Outcome 9 Adverse events.

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Analysis 6.10

Comparison 6 DOAC versus heparin, Outcome 10 Bleeding ‐ major.

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Analysis 6.11

Comparison 6 DOAC versus heparin, Outcome 11 Bleeding ‐ clinically relevant, non‐major.

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Analysis 6.12

Comparison 6 DOAC versus heparin, Outcome 12 Bleeding ‐ minor.

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Analysis 6.13

Comparison 6 DOAC versus heparin, Outcome 13 Reoperation.

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Analysis 6.14

Comparison 6 DOAC versus heparin, Outcome 14 Wound infection.

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Summary of findings for the main comparison. Heparin compared to placebo for prevention of venous thromboembolism following total hip or knee replacement or hip fracture repair

Heparin compared to placebo for prevention of venous thromboembolism following total hip or knee replacement or hip fracture repair
Patient or population: people requiring prevention of venous thromboembolism following total hip or knee replacement or hip fracture repair Setting: hospital and outpatient setting Intervention: heparin Comparison: placebo
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	Number of participants (studies)	Quality of the evidence (GRADE)	Comments
	Risk with placebo	Risk with heparin
Symptomatic VTE (DVT and PE) Treatment duration 28 ‐ 42 days	Study population		OR 0.59 (0.35 to 1.01)	2329 (5 RCTs)	⊕⊕⊕⊕ HIGH	—
	33 per 1000	20 per 1000 (12 to 33)
Symptomatic DVT (proximal or distal) Treatment duration 28 ‐ 42 days	Study population		OR 0.73 (0.39 to 1.38)	2019 (4 RCTs)	⊕⊕⊕⊝ MODERATE ¹	—
	24 per 1000	18 per 1000 (9 to 33)
Symptomatic PE Treatment duration 28 ‐ 42 days	Study population		OR 0.61 (0.16 to 2.33)	1595 (3 RCTs)	⊕⊕⊝⊝ LOW ^{1 2}	—
	6 per 1000	4 per 1000 (1 to 15)
Bleeding ‐ major Treatment duration 28 ‐ 42 days	Study population		OR 0.59 (0.14 to 2.46)	2500 (5 RCTs)	⊕⊕⊕⊝ MODERATE ¹	—
	4 per 1000	2 per 1000 (0 to 9)
Clinically relevant non‐major bleeding Treatment duration 28 ‐ 42 days	see comment		—	—	—	not reported
Bleeding ‐ minor Treatment duration 28 ‐ 42 days	Study population		OR 2.01 (1.43 to 2.81)	2500 (5 RCTs)	⊕⊕⊕⊕ HIGH	—
	46 per 1000	88 per 1000 (65 to 119)
*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; OR: odds ratio; PE: pulmonary embolism; RCT: randomised controlled trial; VTE: venous thromboembolism
GRADE Working Group grades of evidence High quality: We are very confident that the true effect lies close to that of the estimate of the effect Moderate quality: 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 quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect
¹ Downgraded by one level, low number of events leading to imprecision of results ² Downgraded by one level, some heterogeneity present (I² = 49%) leading to wide CIs

Summary of findings for the main comparison. Heparin compared to placebo for prevention of venous thromboembolism following total hip or knee replacement or hip fracture repair

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Summary of findings 2. Vitamin K antagonists compared to placebo for prevention of venous thromboembolism following total hip or knee replacement or hip fracture repair

Vitamin K antagonists compared to placebo for prevention of venous thromboembolism following total hip or knee replacement or hip fracture repair
Patient or population: people requiring prevention of venous thromboembolism following total hip or knee replacement or hip fracture repair Setting: hospital and outpatient setting Intervention: vitamin K antagonists Comparison: placebo
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	Number of participants (studies)	Quality of the evidence (GRADE)	Comments
	Risk with placebo	Risk with vitamin K antagonists
Symptomatic VTE (DVT and PE) Treatment duration 28 ‐ 42 days	Study population		OR 0.10 (0.01 to 1.94)	360 (1 RCT)	⊕⊕⊕⊝ MODERATE ¹	—
	23 per 1000	2 per 1000 (0 to 43)
Symptomatic DVT (proximal or distal) Treatment duration 28 ‐ 42 days	Study population		OR 0.13 (0.01 to 2.62)	360 (1 RCT)	⊕⊕⊕⊝ MODERATE ¹	—
	17 per 1000	2 per 1000 (0 to 43)
Symptomatic PE Treatment duration 28 ‐ 42 days	Study population		OR 0.32 (0.01 to 7.84)	360 (1 RCT)	⊕⊕⊕⊝ MODERATE ¹	—
	6 per 1000	2 per 1000 (0 to 43)
Bleeding ‐ major Treatment duration 28 ‐ 42 days	see comment		OR 2.89 (0.12 to 71.31)	360 (1 RCT)	⊕⊕⊝⊝ LOW ^{1 2}	no events recorded in placebo group
Clinically relevant non‐major bleeding Treatment duration 28 ‐ 42 days	see comment		—	—	—	not reported
Minor bleeding Treatment duration 28 ‐ 42 days	see comment		—	—	—	not reported
*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; OR: odds ratio; PE: pulmonary embolism; RCT: randomised controlled trial; VTE: venous thromboembolism
GRADE Working Group grades of evidence High quality: We are very confident that the true effect lies close to that of the estimate of the effect Moderate quality: 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 quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect
¹ Downgraded by one level, results from a single study only so heterogeneity could not be assessed ² Downgraded by one level, number of events small leading to wide CI and imprecision of results

Summary of findings 2. Vitamin K antagonists compared to placebo for prevention of venous thromboembolism following total hip or knee replacement or hip fracture repair

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Summary of findings 3. DOAC compared to placebo for prevention of venous thromboembolism following total hip or knee replacement or hip fracture repair

DOAC compared to placebo for prevention of venous thromboembolism following total hip or knee replacement or hip fracture repair
Patient or population: people requiring prevention of venous thromboembolism following total hip or knee replacement or hip fracture repair Setting: hospital and outpatient setting Intervention: DOAC Comparison: placebo
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	Number of participants (studies)	Quality of the evidence (GRADE)	Comments
	Risk with placebo	Risk with DOAC
Symptomatic VTE (DVT and PE) Treatment duration 28 ‐ 42 days	Study population		OR 0.20 (0.06 to 0.68)	2419 (1 RCT)	⊕⊕⊕⊝ MODERATE ¹	—
	12 per 1000	3 per 1000 (1 to 8)
Symptomatic DVT (proximal or distal) Treatment duration 28 ‐ 42 days	Study population		OR 0.18 (0.04 to 0.81)	2459 (2 RCTs)	⊕⊕⊕⊕ HIGH	—
	9 per 1000	2 per 1000 (0 to 7)
Symptomatic PE Treatment duration 28 ‐ 42 days	Study population		OR 0.25 (0.03 to 2.25)	1733 (1 RCT)	⊕⊕⊝⊝ LOW ^{1 2}	—
	5 per 1000	1 per 1000 (0 to 10)
Bleeding ‐ major Treatment duration 28 ‐ 42 days	Study population		OR 1.00 (0.06 to 16.02)	2457 (1 RCT)	⊕⊕⊝⊝ LOW ^{1 2}	—
	1 per 1000	1 per 1000 (0 to 13)
Bleeding‐ clinically relevant non‐major Treatment duration 28 ‐ 42 days	Study population		OR 1.22 (0.76 to 1.95)	2457 (1 RCT)	⊕⊕⊕⊝ MODERATE ¹	—
	27 per 1000	33 per 1000 (21 to 51)
Bleeding ‐ minor Treatment duration 28 ‐ 42 days	Study population		OR 1.18 (0.74 to 1.88)	2457 (1 RCT)	⊕⊕⊕⊝ MODERATE ¹	—
	28 per 1000	32 per 1000 (21 to 51)
*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; DOAC: direct oral anticoagulant; DVT: deep vein thrombosis; OR: odds ratio; PE: pulmonary embolism; RCT: randomised controlled trial; VTE: venous thromboembolism
GRADE Working Group grades of evidence High quality: We are very confident that the true effect lies close to that of the estimate of the effect Moderate quality: 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 quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect
¹ Downgraded by one level, results from a single study so heterogeneity cannot be assessed ² Downgraded by one level, low number of events leading to wide CI and imprecision of results

Summary of findings 3. DOAC compared to placebo for prevention of venous thromboembolism following total hip or knee replacement or hip fracture repair

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Summary of findings 4. Anticoagulants (chosen at investigators' discretion) compared to placebo for prevention of venous thromboembolism following total hip or knee replacement or hip fracture repair

Anticoagulants (chosen at investigators' discretion) compared to placebo for prevention of venous thromboembolism following total hip or knee replacement or hip fracture repair
Patient or population: people requiring prevention of venous thromboembolism following total hip or knee replacement or hip fracture repair Setting: hospital and outpatient setting Intervention: anticoagulant (chosen at investigators' discretion) Comparison: placebo
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	Number of participants (studies)	Quality of the evidence (GRADE)	Comments
	Risk with placebo	Risk with anticoagulant (chosen at investigators' discretion)
Symptomatic VTE (DVT and PE) Treatment duration 28 ‐ 42 days	Study population		OR 0.50 (0.09 to 2.74)	557 (1 RCT)	⊕⊕⊝⊝ LOW ^{1 2}	—
	14 per 1000	7 per 1000 (1 to 38)
Symptomatic DVT (proximal or distal) Treatment duration 28 ‐ 42 days	Study population		OR 0.33 (0.03 to 3.21)	557 (1 RCT)	⊕⊕⊝⊝ LOW ^{1 2}	—
	11 per 1000	4 per 1000 (0 to 34)
Symptomatic PE Treatment duration 28 ‐ 42 days	Study population		OR 1.00 (0.06 to 16.13)	557 (1 RCT)	⊕⊕⊝⊝ LOW ^{1 2}	—
	4 per 1000	4 per 1000 (0 to 55)
Bleeding ‐ major Treatment duration 28 ‐ 42 days	see comment		OR 5.05 (0.24 to 105.76)	557 (1 RCT)	⊕⊕⊝⊝ LOW ^{1 2}	no major bleeding recorded in the placebo groups
Clinically relevant non‐major bleeding Treatment duration 28 ‐ 42 days	see comment		—	—	—	not reported
Minor bleeding Treatment duration 28 ‐ 42 days	see comment		—	—	—	not reported
*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; OR: odds ratio; PE: pulmonary embolism; RCT: randomised controlled trial; VTE: venous thromboembolism
GRADE Working Group grades of evidence High quality: We are very confident that the true effect lies close to that of the estimate of the effect Moderate quality: 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 quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect
¹ Downgraded by one level, results from a single study so heterogeneity could not be assessed ² Downgraded by one level, low number of events leading to wide CIs and imprecision of results

Summary of findings 4. Anticoagulants (chosen at investigators' discretion) compared to placebo for prevention of venous thromboembolism following total hip or knee replacement or hip fracture repair

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Summary of findings 5. Vitamin K antagonists compared to heparin for prevention of venous thromboembolism following total hip or knee replacement or hip fracture repair

Vitamin K antagonists compared to heparin for prevention of venous thromboembolism following total hip or knee replacement or hip fracture repair
Patient or population: people requiring prevention of venous thromboembolism following total hip or knee replacement or hip fracture repair Setting: hospital and outpatient setting Intervention: vitamin K antagonists Comparison: heparin
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	Number of participants (studies)	Quality of the evidence (GRADE)	Comments
	Risk with heparin	Risk with vitamin K antagonists
Symptomatic VTE (DVT and PE) Treatment duration 28 ‐ 42 days	Study population		OR 1.64 (0.85 to 3.16)	1279 (1 RCT)	⊕⊕⊝⊝ LOW ^{1 2}	—
	23 per 1000	38 per 1000 (20 to 70)
Symptomatic DVT (proximal or distal) Treatment duration 28 ‐ 42 days	Study population		OR 1.36 (0.69 to 2.68)	1279 (1 RCT)	⊕⊕⊝⊝ LOW ^{1 2}	—
	23 per 1000	31 per 1000 (16 to 60)
Symptomatic PE Treatment duration 28 ‐ 42 days	see comment		OR 9.16 (0.49 to 170.42)	1279 (1 RCT)	⊕⊕⊝⊝ LOW ^{1 3}	no cases of symptomatic PE reported in the heparin study arm
Bleeding ‐ major Treatment duration 28 ‐ 42 days	Study population		OR 3.87 (1.91 to 7.85)	1272 (1 RCT)	⊕⊕⊝⊝ LOW ^{1 2}	—
	16 per 1000	58 per 1000 (30 to 111)
Bleeding ‐ clinically indicated non‐major Treatment duration 28 ‐ 42 days	see comment		—	—	—	clinically indicated non‐major bleeding events not reported in single included study in this comparison
Bleeding ‐ minor Treatment duration 28 ‐ 42 days	Study population		OR 1.33 (0.64 to 2.76)	1279 (1 RCT)	⊕⊕⊝⊝ LOW ^{1 2}	—
	20 per 1000	27 per 1000 (13 to 54)
*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; OR: odds ratio; PE: pulmonary embolism; RCT: randomised controlled trial; VKA: vitamin K antagonist; VTE: venous thromboembolism
GRADE Working Group grades of evidence High quality: We are very confident that the true effect lies close to that of the estimate of the effect Moderate quality: 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 quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect
¹ Downgraded by one level, single study so heterogeneity could not be assessed ² Downgraded by one level, wide CI ³ Downgraded by one level, low number of events leading to imprecision of results

Summary of findings 5. Vitamin K antagonists compared to heparin for prevention of venous thromboembolism following total hip or knee replacement or hip fracture repair

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Summary of findings 6. DOAC compared to heparin for people requiring prevention of venous thromboembolism following total hip or knee replacement or hip fracture repair

DOAC compared to heparin for people requiring prevention of venous thromboembolism following total hip or knee replacement or hip fracture repair
Patient or population: people requiring prevention of venous thromboembolism following total hip or knee replacement or hip fracture repair Setting: hospital and outpatient setting Intervention: DOAC Comparison: heparin
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	Number of participants (studies)	Quality of the evidence (GRADE)	Comments
	Risk with heparin	Risk with DOAC
Symptomatic VTE (DVT and PE) Treatment duration 28 ‐ 42 days	Study population		OR 0.70 (0.28 to 1.70)	15977 (5 RCTs)	⊕⊕⊝⊝ LOW ^{1 2}	—
	4 per 1000	3 per 1000 (1 to 8)
Symptomatic DVT (proximal or distal) Treatment duration 28 ‐ 42 days	Study population		OR 0.60 (0.11 to 3.27)	15977 (5 RCTs)	⊕⊕⊝⊝ LOW ^{2 3}	—
	3 per 1000	2 per 1000 (0 to 9)
Symptomatic PE Treatment duration 28 ‐ 42 days	Study population		OR 0.91 (0.43 to 1.94)	14731 (5 RCTs)	⊕⊕⊕⊝ MODERATE ²	—
	2 per 1000	2 per 1000 (1 to 4)
Bleeding ‐ major Treatment duration 28 ‐ 42 days	Study population		OR 1.11 (0.79 to 1.54)	16199 (5 RCTs)	⊕⊕⊕⊕ HIGH	—
	8 per 1000	9 per 1000 (7 to 13)
Bleeding ‐ clinically relevant, non‐major Treatment duration 28 ‐ 42 days	Study population		OR 1.08 (0.90 to 1.28)	15241 (4 RCTs)	⊕⊕⊕⊕ HIGH	—
	33 per 1000	36 per 1000 (30 to 42)
Bleeding ‐ minor Treatment duration 28 ‐ 42 days	Study population		OR 0.95 (0.82 to 1.10)	11766 (4 RCTs)	⊕⊕⊕⊕ HIGH	—
	66 per 1000	63 per 1000 (55 to 72)
*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; DOAC: direct oral anticoagulant; DVT: deep vein thrombosis; OR: odds ratio; PE: pulmonary embolism; RCT: randomised controlled trial; VTE: venous thromboembolism
GRADE Working Group grades of evidence High quality: We are very confident that the true effect lies close to that of the estimate of the effect Moderate quality: 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 quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect
¹ Downgraded by one level for inconsistency (heterogeneity, I² = 55%) ² Downgraded by one level for imprecision due to low number of events leading to wide CI ³ Downgraded by one level for inconsistency (heterogeneity, I² = 65%)

Summary of findings 6. DOAC compared to heparin for people requiring prevention of venous thromboembolism following total hip or knee replacement or hip fracture repair

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Comparison 1. Heparin versus placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Symptomatic VTE (DVT and PE) Show forest plot	5	2329	Odds Ratio (M‐H, Fixed, 95% CI)	0.59 [0.35, 1.01]

1.1 Hip replacement	4	1296	Odds Ratio (M‐H, Fixed, 95% CI)	0.69 [0.36, 1.30]
1.2 Knee replacement	1	723	Odds Ratio (M‐H, Fixed, 95% CI)	0.78 [0.21, 2.92]
1.3 Hip or knee replacement	1	310	Odds Ratio (M‐H, Fixed, 95% CI)	0.22 [0.05, 1.06]
2 Symptomatic DVT (proximal or distal) Show forest plot	4	2019	Odds Ratio (M‐H, Fixed, 95% CI)	0.73 [0.39, 1.38]

2.1 Hip replacement	4	1296	Odds Ratio (M‐H, Fixed, 95% CI)	0.80 [0.41, 1.55]
2.2 Knee replacement	1	723	Odds Ratio (M‐H, Fixed, 95% CI)	0.32 [0.03, 3.12]
3 Symptomatic PE Show forest plot	3	1595	Odds Ratio (M‐H, Fixed, 95% CI)	0.61 [0.16, 2.33]

3.1 Hip replacement	3	872	Odds Ratio (M‐H, Fixed, 95% CI)	0.13 [0.01, 2.56]
3.2 Knee replacement	1	723	Odds Ratio (M‐H, Fixed, 95% CI)	1.47 [0.24, 8.83]
4 Total VTE (symptomatic and asymptomatic) Show forest plot	6	2544	Odds Ratio (M‐H, Fixed, 95% CI)	0.39 [0.28, 0.56]

4.1 Hip replacement	5	1511	Odds Ratio (M‐H, Fixed, 95% CI)	0.37 [0.25, 0.56]
4.2 Knee replacement	1	723	Odds Ratio (M‐H, Fixed, 95% CI)	0.78 [0.21, 2.92]
4.3 Hip or knee replacement	1	310	Odds Ratio (M‐H, Fixed, 95% CI)	0.38 [0.16, 0.90]
5 Asymptomatic DVT Show forest plot	5	1304	Odds Ratio (M‐H, Fixed, 95% CI)	0.38 [0.24, 0.60]

5.1 Hip replacement	4	994	Odds Ratio (M‐H, Fixed, 95% CI)	0.35 [0.21, 0.58]
5.2 Hip or knee replacement	1	310	Odds Ratio (M‐H, Fixed, 95% CI)	0.54 [0.19, 1.52]
6 All‐cause mortality Show forest plot	5	2518	Odds Ratio (M‐H, Fixed, 95% CI)	1.01 [0.31, 3.26]

6.1 Hip replacement	4	1485	Odds Ratio (M‐H, Fixed, 95% CI)	0.56 [0.11, 2.75]
6.2 Knee replacement	1	723	Odds Ratio (M‐H, Fixed, 95% CI)	0.98 [0.06, 15.65]
6.3 Hip or knee replacement	1	310	Odds Ratio (M‐H, Fixed, 95% CI)	4.69 [0.22, 98.42]
7 Adverse events Show forest plot	2	460	Odds Ratio (M‐H, Fixed, 95% CI)	1.06 [0.68, 1.64]

7.1 Hip replacement	2	460	Odds Ratio (M‐H, Fixed, 95% CI)	1.06 [0.68, 1.64]
8 Bleeding ‐ major Show forest plot	5	2500	Odds Ratio (M‐H, Fixed, 95% CI)	0.59 [0.14, 2.46]

8.1 Hip replacement	4	1494	Odds Ratio (M‐H, Fixed, 95% CI)	0.32 [0.03, 3.10]
8.2 Knee replacement	1	696	Odds Ratio (M‐H, Fixed, 95% CI)	0.99 [0.14, 7.06]
8.3 Hip or knee replacement	1	310	Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
9 Bleeding ‐ minor Show forest plot	5	2500	Odds Ratio (M‐H, Fixed, 95% CI)	2.01 [1.43, 2.81]

9.1 Hip replacement	4	1494	Odds Ratio (M‐H, Fixed, 95% CI)	2.25 [1.53, 3.30]
9.2 Knee replacement	1	696	Odds Ratio (M‐H, Fixed, 95% CI)	1.23 [0.58, 2.59]
9.3 Hip or knee replacement	1	310	Odds Ratio (M‐H, Fixed, 95% CI)	2.79 [0.11, 69.13]
10 Reoperation Show forest plot	1	179	Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]

10.1 Hip replacement	1	179	Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]

Comparison 1. Heparin versus placebo

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Comparison 2. Vitamin K antagonists versus placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Symptomatic VTE (DVT and PE) Show forest plot	1	360	Odds Ratio (M‐H, Fixed, 95% CI)	0.10 [0.01, 1.94]

1.1 Hip replacement	1	360	Odds Ratio (M‐H, Fixed, 95% CI)	0.10 [0.01, 1.94]
2 Symptomatic DVT (proximal or distal) Show forest plot	1	360	Odds Ratio (M‐H, Fixed, 95% CI)	0.13 [0.01, 2.62]

2.1 Hip replacement	1	360	Odds Ratio (M‐H, Fixed, 95% CI)	0.13 [0.01, 2.62]
3 Symptomatic PE Show forest plot	1	360	Odds Ratio (M‐H, Fixed, 95% CI)	0.32 [0.01, 7.84]

3.1 Hip replacement	1	360	Odds Ratio (M‐H, Fixed, 95% CI)	0.32 [0.01, 7.84]
4 Total VTE (symptomatic and asymptomatic) Show forest plot	1	360	Odds Ratio (M‐H, Fixed, 95% CI)	0.10 [0.01, 0.81]

4.1 Hip replacement	1	360	Odds Ratio (M‐H, Fixed, 95% CI)	0.10 [0.01, 0.81]
5 All‐cause mortality Show forest plot	1	360	Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]

5.1 Hip replacement	1	360	Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
6 Adverse events Show forest plot	1	360	Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]

6.1 Hip replacement	1	360	Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
7 Bleeding ‐ major Show forest plot	1	360	Odds Ratio (M‐H, Fixed, 95% CI)	2.89 [0.12, 71.31]

7.1 Hip replacement	1	360	Odds Ratio (M‐H, Fixed, 95% CI)	2.89 [0.12, 71.31]

Comparison 2. Vitamin K antagonists versus placebo

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Comparison 3. DOAC versus placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Symptomatic VTE (DVT and PE) Show forest plot	1	2419	Odds Ratio (M‐H, Fixed, 95% CI)	0.20 [0.06, 0.68]

1.1 Hip replacement	1	2419	Odds Ratio (M‐H, Fixed, 95% CI)	0.20 [0.06, 0.68]
2 Symptomatic DVT (proximal or distal) Show forest plot	2	2459	Odds Ratio (M‐H, Fixed, 95% CI)	0.18 [0.04, 0.81]

2.1 Hip replacement	2	2459	Odds Ratio (M‐H, Fixed, 95% CI)	0.18 [0.04, 0.81]
3 Symptomatic PE Show forest plot	1	1733	Odds Ratio (M‐H, Fixed, 95% CI)	0.25 [0.03, 2.25]

3.1 Hip replacement	1	1733	Odds Ratio (M‐H, Fixed, 95% CI)	0.25 [0.03, 2.25]
4 Total VTE (symptomatic and asymptomatic) Show forest plot	1	1733	Odds Ratio (M‐H, Fixed, 95% CI)	0.19 [0.11, 0.33]

4.1 Hip replacement	1	1733	Odds Ratio (M‐H, Fixed, 95% CI)	0.19 [0.11, 0.33]
5 All‐cause mortality Show forest plot	1	1733	Odds Ratio (M‐H, Fixed, 95% CI)	0.33 [0.07, 1.66]

5.1 Hip replacement	1	1733	Odds Ratio (M‐H, Fixed, 95% CI)	0.33 [0.07, 1.66]
6 Adverse events Show forest plot	1	2457	Odds Ratio (M‐H, Fixed, 95% CI)	0.87 [0.74, 1.03]

6.1 Hip replacement	1	2457	Odds Ratio (M‐H, Fixed, 95% CI)	0.87 [0.74, 1.03]
7 Bleeding ‐ major Show forest plot	1	2457	Odds Ratio (M‐H, Fixed, 95% CI)	1.00 [0.06, 16.02]

7.1 Hip replacement	1	2457	Odds Ratio (M‐H, Fixed, 95% CI)	1.00 [0.06, 16.02]
8 Bleeding‐ clinically relevant non‐major Show forest plot	1	2457	Odds Ratio (M‐H, Fixed, 95% CI)	1.22 [0.76, 1.95]

8.1 Hip replacement	1	2457	Odds Ratio (M‐H, Fixed, 95% CI)	1.22 [0.76, 1.95]
9 Bleeding ‐ minor Show forest plot	1	2457	Odds Ratio (M‐H, Fixed, 95% CI)	1.18 [0.74, 1.88]

9.1 Hip replacement	1	2457	Odds Ratio (M‐H, Fixed, 95% CI)	1.18 [0.74, 1.88]
10 Reoperation Show forest plot	1	2457	Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]

10.1 Hip replacement	1	2457	Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
11 Wound infection Show forest plot	1	2457	Odds Ratio (M‐H, Fixed, 95% CI)	1.34 [0.46, 3.86]

11.1 Hip replacement	1	2457	Odds Ratio (M‐H, Fixed, 95% CI)	1.34 [0.46, 3.86]

Comparison 3. DOAC versus placebo

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Comparison 4. Anticoagulant (chosen at investigators' discretion) versus placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Symptomatic VTE (DVT and PE) Show forest plot	1	557	Odds Ratio (M‐H, Fixed, 95% CI)	0.50 [0.09, 2.74]

1.1 Knee replacement	1	557	Odds Ratio (M‐H, Fixed, 95% CI)	0.50 [0.09, 2.74]
2 Symptomatic DVT (proximal or distal) Show forest plot	1	557	Odds Ratio (M‐H, Fixed, 95% CI)	0.33 [0.03, 3.21]

2.1 Knee replacement	1	557	Odds Ratio (M‐H, Fixed, 95% CI)	0.33 [0.03, 3.21]
3 Symptomatic PE Show forest plot	1	557	Odds Ratio (M‐H, Fixed, 95% CI)	1.00 [0.06, 16.13]

3.1 Knee replacement	1	557	Odds Ratio (M‐H, Fixed, 95% CI)	1.00 [0.06, 16.13]
4 Total VTE (symptomatic and asymptomatic) Show forest plot	1	557	Odds Ratio (M‐H, Fixed, 95% CI)	0.26 [0.14, 0.50]

4.1 Knee replacement	1	557	Odds Ratio (M‐H, Fixed, 95% CI)	0.26 [0.14, 0.50]
5 Asymptomatic DVT Show forest plot	1	557	Odds Ratio (M‐H, Fixed, 95% CI)	0.26 [0.13, 0.54]

5.1 Knee replacement	1	557	Odds Ratio (M‐H, Fixed, 95% CI)	0.26 [0.13, 0.54]
6 Asymptomatic distal DVT Show forest plot	1	557	Odds Ratio (M‐H, Fixed, 95% CI)	0.26 [0.13, 0.54]

6.1 Knee replacement	1	557	Odds Ratio (M‐H, Fixed, 95% CI)	0.26 [0.13, 0.54]
7 All‐cause mortality Show forest plot	1	842	Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]

7.1 Knee replacement	1	842	Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
8 Bleeding ‐ major Show forest plot	1	557	Odds Ratio (M‐H, Fixed, 95% CI)	5.05 [0.24, 105.76]

8.1 Knee replacement	1	557	Odds Ratio (M‐H, Fixed, 95% CI)	5.05 [0.24, 105.76]

Comparison 4. Anticoagulant (chosen at investigators' discretion) versus placebo

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Comparison 5. Vitamin K antagonists versus heparin

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Symptomatic VTE (DVT and PE) Show forest plot	1	1279	Odds Ratio (M‐H, Fixed, 95% CI)	1.64 [0.85, 3.16]

1.1 Hip replacement	1	1279	Odds Ratio (M‐H, Fixed, 95% CI)	1.64 [0.85, 3.16]
2 Symptomatic DVT (proximal or distal) Show forest plot	1	1279	Odds Ratio (M‐H, Fixed, 95% CI)	1.36 [0.69, 2.68]

2.1 Hip replacement	1	1279	Odds Ratio (M‐H, Fixed, 95% CI)	1.36 [0.69, 2.68]
3 Symptomatic PE Show forest plot	1	1279	Odds Ratio (M‐H, Fixed, 95% CI)	9.16 [0.49, 170.42]

3.1 Hip replacement	1	1279	Odds Ratio (M‐H, Fixed, 95% CI)	9.16 [0.49, 170.42]
4 Total VTE (symptomatic and asymptomatic) Show forest plot	1	1279	Odds Ratio (M‐H, Fixed, 95% CI)	1.64 [0.85, 3.16]

4.1 Hip replacement	1	1279	Odds Ratio (M‐H, Fixed, 95% CI)	1.64 [0.85, 3.16]
5 All‐cause mortality Show forest plot	1	1279	Odds Ratio (M‐H, Fixed, 95% CI)	5.07 [0.24, 105.83]

5.1 Hip replacement	1	1279	Odds Ratio (M‐H, Fixed, 95% CI)	5.07 [0.24, 105.83]
6 Bleeding ‐ major Show forest plot	1	1272	Odds Ratio (M‐H, Fixed, 95% CI)	3.87 [1.91, 7.85]

6.1 Hip replacement	1	1272	Odds Ratio (M‐H, Fixed, 95% CI)	3.87 [1.91, 7.85]
7 Bleeding ‐ minor Show forest plot	1	1279	Odds Ratio (M‐H, Fixed, 95% CI)	1.33 [0.64, 2.76]

7.1 Hip replacement	1	1279	Odds Ratio (M‐H, Fixed, 95% CI)	1.33 [0.64, 2.76]
8 Reoperation Show forest plot	1	1279	Odds Ratio (M‐H, Fixed, 95% CI)	4.60 [0.99, 21.38]

8.1 Hip replacement	1	1279	Odds Ratio (M‐H, Fixed, 95% CI)	4.60 [0.99, 21.38]

Comparison 5. Vitamin K antagonists versus heparin

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Comparison 6. DOAC versus heparin

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Symptomatic VTE (DVT and PE) Show forest plot	5	15977	Odds Ratio (M‐H, Random, 95% CI)	0.70 [0.28, 1.70]

1.1 Hip replacement	5	15977	Odds Ratio (M‐H, Random, 95% CI)	0.70 [0.28, 1.70]
2 Symptomatic DVT (proximal or distal) Show forest plot	5	15977	Odds Ratio (M‐H, Random, 95% CI)	0.60 [0.11, 3.27]

2.1 Hip replacement	5	15977	Odds Ratio (M‐H, Random, 95% CI)	0.60 [0.11, 3.27]
3 Symptomatic PE Show forest plot	5	14731	Odds Ratio (M‐H, Fixed, 95% CI)	0.91 [0.43, 1.94]

3.1 Hip replacement	5	14731	Odds Ratio (M‐H, Fixed, 95% CI)	0.91 [0.43, 1.94]
4 Total VTE (symptomatic and asymptomatic) Show forest plot	4	12447	Odds Ratio (M‐H, Random, 95% CI)	0.53 [0.29, 0.97]

4.1 Hip replacement	4	12447	Odds Ratio (M‐H, Random, 95% CI)	0.53 [0.29, 0.97]
5 Asymptomatic DVT Show forest plot	2	6559	Odds Ratio (M‐H, Random, 95% CI)	0.56 [0.19, 1.59]

5.1 Hip replacement	2	6559	Odds Ratio (M‐H, Random, 95% CI)	0.56 [0.19, 1.59]
6 Asymptomatic proximal DVT Show forest plot	1	2704	Odds Ratio (M‐H, Fixed, 95% CI)	0.73 [0.46, 1.15]

6.1 Hip replacement	1	2704	Odds Ratio (M‐H, Fixed, 95% CI)	0.73 [0.46, 1.15]
7 Asymptomatic distal DVT Show forest plot	1	2639	Odds Ratio (M‐H, Fixed, 95% CI)	1.22 [0.75, 1.99]

7.1 Hip replacement	1	2639	Odds Ratio (M‐H, Fixed, 95% CI)	1.22 [0.75, 1.99]
8 All‐cause mortality Show forest plot	5	14966	Odds Ratio (M‐H, Fixed, 95% CI)	1.63 [0.64, 4.16]

8.1 Hip replacement	5	14966	Odds Ratio (M‐H, Fixed, 95% CI)	1.63 [0.64, 4.16]
9 Adverse events Show forest plot	3	9908	Odds Ratio (M‐H, Fixed, 95% CI)	0.96 [0.88, 1.05]

9.1 Hip replacement	3	9908	Odds Ratio (M‐H, Fixed, 95% CI)	0.96 [0.88, 1.05]
10 Bleeding ‐ major Show forest plot	5	16199	Odds Ratio (M‐H, Fixed, 95% CI)	1.11 [0.79, 1.54]

10.1 Hip replacement	5	16199	Odds Ratio (M‐H, Fixed, 95% CI)	1.11 [0.79, 1.54]
11 Bleeding ‐ clinically relevant, non‐major Show forest plot	4	15241	Odds Ratio (M‐H, Fixed, 95% CI)	1.08 [0.90, 1.28]

11.1 Hip replacement	4	15241	Odds Ratio (M‐H, Fixed, 95% CI)	1.08 [0.90, 1.28]
12 Bleeding ‐ minor Show forest plot	4	11766	Odds Ratio (M‐H, Fixed, 95% CI)	0.95 [0.82, 1.10]

12.1 Hip replacement	4	11766	Odds Ratio (M‐H, Fixed, 95% CI)	0.95 [0.82, 1.10]
13 Reoperation Show forest plot	4	15241	Odds Ratio (M‐H, Fixed, 95% CI)	1.06 [0.34, 3.24]

13.1 Hip replacement	4	15241	Odds Ratio (M‐H, Fixed, 95% CI)	1.06 [0.34, 3.24]
14 Wound infection Show forest plot	2	6446	Odds Ratio (M‐H, Fixed, 95% CI)	0.89 [0.46, 1.72]

14.1 Hip replacement	2	6446	Odds Ratio (M‐H, Fixed, 95% CI)	0.89 [0.46, 1.72]

Comparison 6. DOAC versus heparin

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Anticoagulantes (de duración prolongada) para la prevención de la tromboembolia venosa posterior al reemplazo total de rodilla o cadera o la reparación de la fractura de cadera

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