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PRISMA study flow diagram
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Figure 1

PRISMA study flow diagram

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Risk of bias graph: review authors' judgements about each risk of bias domain, presented as percentages across all included studies
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Figure 2

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

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Risk of bias summary: review authors' judgements about each risk of bias domain for each included study
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Figure 3

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

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Comparison 1 Low molecular weight heparin versus no prophylaxis or placebo, Outcome 1 Deep venous thrombosis: regardless of type of plaster, whether operated or not.
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Analysis 1.1

Comparison 1 Low molecular weight heparin versus no prophylaxis or placebo, Outcome 1 Deep venous thrombosis: regardless of type of plaster, whether operated or not.

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Comparison 1 Low molecular weight heparin versus no prophylaxis or placebo, Outcome 2 Deep venous thrombosis: in below‐knee cast, whether operated or not.
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Analysis 1.2

Comparison 1 Low molecular weight heparin versus no prophylaxis or placebo, Outcome 2 Deep venous thrombosis: in below‐knee cast, whether operated or not.

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Comparison 1 Low molecular weight heparin versus no prophylaxis or placebo, Outcome 3 Deep venous thrombosis: conservative treatment (i.e. non‐operated patients).
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Analysis 1.3

Comparison 1 Low molecular weight heparin versus no prophylaxis or placebo, Outcome 3 Deep venous thrombosis: conservative treatment (i.e. non‐operated patients).

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Comparison 1 Low molecular weight heparin versus no prophylaxis or placebo, Outcome 4 Deep venous thrombosis: operated patients.
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Analysis 1.4

Comparison 1 Low molecular weight heparin versus no prophylaxis or placebo, Outcome 4 Deep venous thrombosis: operated patients.

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Comparison 1 Low molecular weight heparin versus no prophylaxis or placebo, Outcome 5 Deep venous thrombosis: fractures.
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Analysis 1.5

Comparison 1 Low molecular weight heparin versus no prophylaxis or placebo, Outcome 5 Deep venous thrombosis: fractures.

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Comparison 1 Low molecular weight heparin versus no prophylaxis or placebo, Outcome 6 Deep venous thrombosis: soft‐tissue injuries.
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Analysis 1.6

Comparison 1 Low molecular weight heparin versus no prophylaxis or placebo, Outcome 6 Deep venous thrombosis: soft‐tissue injuries.

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Comparison 1 Low molecular weight heparin versus no prophylaxis or placebo, Outcome 7 Deep venous thrombosis: distal segment.
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Analysis 1.7

Comparison 1 Low molecular weight heparin versus no prophylaxis or placebo, Outcome 7 Deep venous thrombosis: distal segment.

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Comparison 1 Low molecular weight heparin versus no prophylaxis or placebo, Outcome 8 Deep venous thrombosis: proximal segment.
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Analysis 1.8

Comparison 1 Low molecular weight heparin versus no prophylaxis or placebo, Outcome 8 Deep venous thrombosis: proximal segment.

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Comparison 1 Low molecular weight heparin versus no prophylaxis or placebo, Outcome 9 Pulmonary embolism.
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Analysis 1.9

Comparison 1 Low molecular weight heparin versus no prophylaxis or placebo, Outcome 9 Pulmonary embolism.

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Comparison 1 Low molecular weight heparin versus no prophylaxis or placebo, Outcome 10 Symptomatic venous thromboembolism.
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Analysis 1.10

Comparison 1 Low molecular weight heparin versus no prophylaxis or placebo, Outcome 10 Symptomatic venous thromboembolism.

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Comparison 1 Low molecular weight heparin versus no prophylaxis or placebo, Outcome 11 Mortality due to pulmonary embolism.
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Analysis 1.11

Comparison 1 Low molecular weight heparin versus no prophylaxis or placebo, Outcome 11 Mortality due to pulmonary embolism.

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Comparison 1 Low molecular weight heparin versus no prophylaxis or placebo, Outcome 12 Mortality due to other causes.
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Analysis 1.12

Comparison 1 Low molecular weight heparin versus no prophylaxis or placebo, Outcome 12 Mortality due to other causes.

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Comparison 1 Low molecular weight heparin versus no prophylaxis or placebo, Outcome 13 Adverse outcomes.
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Analysis 1.13

Comparison 1 Low molecular weight heparin versus no prophylaxis or placebo, Outcome 13 Adverse outcomes.

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Summary of findings for the main comparison. Low molecular weight heparin compared to no prophylaxis or placebo in prevention of venous thromboembolism in patients with lower‐limb immobilization

Low molecular weight heparin compared to no prophylaxis or placebo in prevention of venous thromboembolism in patients with lower‐limb immobilization

Patient or population: prevention of venous thromboembolism in patients with lower‐limb immobilization
Setting: ambulatory setting
Intervention: low molecular weight heparin
Comparison: no prophylaxis or placebo

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with no prophylaxis or placebo

Risk with low molecular weight heparin

Deep venous thrombosis

Study population

OR 0.45
(0.33 to 0.61)

1676
(7 RCTs)

⊕⊕⊕⊝
MODERATE 1

174 per 1000

87 per 1000
(65 to 114)

Pulmonary embolism

Study population

OR 0.50
(0.17 to 1.47)

2517
(5 RCTs)

⊕⊕⊝⊝
LOW 2

7 per 1000

4 per 1000
(1 to 10)

Symptomatic venous thromboembolism

Study population

OR 0.40
(0.21 to 0.76)

2924
(6 RCTs)

⊕⊕⊝⊝
LOW 3

21 per 1000

9 per 1000
(5 to 16)

Mortality due to pulmonary embolism

Study population

‐

3111
(8 RCTs)

‐

No mortality due to pulmonary embolism was reported

see comment

see comment

Mortality due to other causes

Study population

OR 0.33

(0.01 to 8.15)

3111
(8 RCTs)

⊕⊕⊝⊝
LOW 4

One death (in no prophylaxis/placebo group) was reported in the included studies

1 per 1000

0 per 1000

(0 to 5)

Adverse outcomes

Study population

OR 2.01
(0.83 to 4.86)

3178
(8 RCTs)

⊕⊕⊝⊝
LOW 5

40 per 1000

78 per 1000
(34 to 170)

*We calculated the assumed risk of the no prophylaxis or placebo group from the average risk in the no prophylaxis or placebo groups (i.e. the number of participants with events divided by total number of participants of the no prophylaxis or placebo group included in the meta‐analysis). 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; OR: odds ratio;

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 as 3 out of 7 studies showed considerable risk of bias
2 Downgraded by two levels as 2 out of 5 studies showed considerable risk of bias, and imprecision of pooled results
3 Downgraded by two levels as 3 out of 6 studies showed considerable risk of bias, and imprecision of pooled results
4 Downgraded by two levels due to the low number of events, and imprecision of pooled results
5 Downgraded by two levels as 4 out of 8 studies showed considerable risk of bias, and imprecision of pooled results

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Summary of findings for the main comparison. Low molecular weight heparin compared to no prophylaxis or placebo in prevention of venous thromboembolism in patients with lower‐limb immobilization
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Comparison 1. Low molecular weight heparin versus no prophylaxis or placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Deep venous thrombosis: regardless of type of plaster, whether operated or not Show forest plot

7

1676

Odds Ratio (M‐H, Fixed, 95% CI)

0.45 [0.33, 0.61]

2 Deep venous thrombosis: in below‐knee cast, whether operated or not Show forest plot

6

1080

Odds Ratio (M‐H, Fixed, 95% CI)

0.49 [0.34, 0.72]

3 Deep venous thrombosis: conservative treatment (i.e. non‐operated patients) Show forest plot

5

974

Odds Ratio (M‐H, Fixed, 95% CI)

0.31 [0.18, 0.53]

4 Deep venous thrombosis: operated patients Show forest plot

4

699

Odds Ratio (M‐H, Fixed, 95% CI)

0.54 [0.37, 0.80]

5 Deep venous thrombosis: fractures Show forest plot

6

1003

Odds Ratio (M‐H, Fixed, 95% CI)

0.48 [0.33, 0.70]

6 Deep venous thrombosis: soft‐tissue injuries Show forest plot

5

658

Odds Ratio (M‐H, Fixed, 95% CI)

0.39 [0.22, 0.68]

7 Deep venous thrombosis: distal segment Show forest plot

5

1208

Odds Ratio (M‐H, Fixed, 95% CI)

0.61 [0.42, 0.89]

8 Deep venous thrombosis: proximal segment Show forest plot

5

1217

Odds Ratio (M‐H, Fixed, 95% CI)

0.41 [0.19, 0.91]

9 Pulmonary embolism Show forest plot

5

2517

Odds Ratio (M‐H, Fixed, 95% CI)

0.50 [0.17, 1.47]

10 Symptomatic venous thromboembolism Show forest plot

6

2924

Odds Ratio (M‐H, Fixed, 95% CI)

0.40 [0.21, 0.76]

11 Mortality due to pulmonary embolism Show forest plot

8

3111

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

12 Mortality due to other causes Show forest plot

8

3111

Odds Ratio (M‐H, Fixed, 95% CI)

0.33 [0.01, 8.15]

13 Adverse outcomes Show forest plot

8

3178

Odds Ratio (M‐H, Random, 95% CI)

2.01 [0.83, 4.86]
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Comparison 1. Low molecular weight heparin versus no prophylaxis or placebo
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