#1

MeSH descriptor: [Thrombosis] this term only

1309

#2

MeSH descriptor: [Thromboembolism] this term only

1067

#3

MeSH descriptor: [Venous Thromboembolism] this term only

461

#4

MeSH descriptor: [Venous Thrombosis] this term only

1060

#5

(thromboprophyla* or thrombus* or thrombotic* or thrombolic* or thromboemboli* or thrombos* or embol*):ti,ab,kw

17234

#6

MeSH descriptor: [Pulmonary Embolism] explode all trees

944

#7

PE or DVT or VTE:ti,ab,kw

4161

#8

(vein* or ven*) near thromb*:ti,ab,kw

6917

#9

#1 or #2 or #3 or #4 or #5 or #6 or #7 or #8

20147

#10

MeSH descriptor: [Anticoagulants] explode all trees

4058

#11

anticoagul* or anti‐coagu* or antithrombotic*

9328

#12

warfarin or (vitamin near/3 antagonist*) or VKA or Nicoumalone or phenindione or acenocoumarol* or Sinthrome or dicoumarol* or nicoumalone or phenprocoumon or Marcoumar or Marcumar or Falithrom or AVK or bishydroxycoumarin* or coumarin* or coumadin* or phenprocoumon*

4024

#13

Ximelagatran or Exanta or Exarta or H 376/95 or dabigatran or rivaroxaban or Xarelto

874

#14

fondaparinux or Arixtra or BAY59‐7939 or TTP889 or odiparcil or LY517717 or YM150 or DU‐176b

395

#15

apixaban or betrixaban or edoxaban or idraparinux

402

#16

LMWH or UFH or heparin or nadroparin* or fraxiparin* or enoxaparin

9899

#17

Clexane or klexane or lovenox or dalteparin or Fragmin or ardeparin

762

#18

normiflo or tinzaparin or logiparin or Innohep or certoparin or sandoparin or reviparin or clivarin*

432

#19

danaproid or danaparoid or antixarin or ardeparin* or bemiparin*

136

#20

Zibor or cy 222 or embolex or monoembolex or parnaparin*

128

#21

rd 11885 or tedelparin or Kabi‐2165 or Kabi 2165

78

#22

emt‐966 or emt‐967 or "pk‐10 169" or pk‐10169 or pk10169 or cy‐216 or cy216

83

#23

seleparin* or tedegliparin or seleparin* or tedegliparin*

19

#24

wy90493 or "wy 90493" or "kb 101" or kb101

21

#25

lomoparan or orgaran or parnaparin or fluxum or lohepa or lowhepa or "op 2123" or parvoparin or AVE5026

113

#26

#10 or #11 or #12 or #13 or #14 or #15 or #16 or #17 or #18 or #19 or #20 or #21 or #22 or #23 or #24 or #25

17458

#27

MeSH descriptor: [Hip] explode all trees

309

#28

MeSH descriptor: [Knee] explode all trees

584

#29

hip:ti,ab,kw (Word variations have been searched)

11495

#30

knee:ti,ab,kw (Word variations have been searched)

13133

#31

orthop?edic

6896

#32

MeSH descriptor: [Orthopedic Procedures] explode all trees

10000

#33

#27 or #28 or #29 or #30 or #31 or #32

31372

#34

#9 and #26 and #33

1182

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

Total VTE (symptomatic and asymptomatic)

Treatment duration 28 ‐ 42 days

Study population

OR 0.39
(0.28 to 0.56)

2544
(6 RCTs)

⊕⊕⊕⊕
HIGH

—

83 per 1000

34 per 1000
(25 to 48)

Asymptomatic DVT

Treatment duration 28 ‐ 42 days

Study population

OR 0.38
(0.24 to 0.60)

1304
(5 RCTs)

⊕⊕⊕⊕
HIGH

—

112 per 1000

46 per 1000
(29 to 71)

Asymptomatic proximal DVT

Treatment duration 28 ‐ 42 days

see comment

not estimable

—

—

asymptomatic and proximal DVT reported separately but due to available data it was not possible to determine which events fell into which category

Asymptomatic distal DVT

Treatment duration 28 ‐ 42 days

see comment

not estimable

—

—

asymptomatic and distal DVT reported separately but due to available data it was not possible to determine which events fell into which category

All‐cause mortality

Treatment duration 28 ‐ 42 days

Study population

OR 1.01
(0.31 to 3.26)

2518
(5 RCTs)

⊕⊕⊕⊝
MODERATE ¹

—

4 per 1000

4 per 1000
(1 to 11)

Adverse events

Treatment duration 28 ‐ 42 days

Study population

OR 1.06
(0.68 to 1.64)

460
(2 RCTs)

⊕⊕⊕⊝
MODERATE ²

—

270 per 1000

281 per 1000
(201 to 377)

Reoperation
Treatment duration 28 ‐ 42 days

see comment

—

179
(1 RCT)

—

one study reported no operations in either study arm. Three studies did not report on reoperation and two studies did not report sufficient data to analyse

Wound infection

Treatment duration 28 ‐ 42 days

see comment

—

—

—

four studies did not report on wound infection. Two studies did not provide specific details for wound infection

Wound healing

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

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

Total VTE (symptomatic and asymptomatic)
Treatment duration 28 ‐ 42 days

Study population

OR 0.10
(0.01 to 0.81)

360
(1 RCT)

⊕⊕⊕⊝
MODERATE ¹

—

51 per 1000

5 per 1000
(1 to 42)

Asymptomatic DVT

Treatment duration 28 ‐ 42 days

see comment

—

—

—

not reported in single included study in this comparison

Asymptomatic proximal DVT

Treatment duration 28 ‐ 42 days

see comment

—

—

—

not reported in single included study in this comparison

Asymptomatic distal DVT

Treatment duration 28 ‐ 42 days

see comment

—

—

—

not reported in single included study in this comparison

All‐cause mortality

Treatment duration 28 ‐ 42 days

see comment

—

360
(1 RCT)

—

single included study reported no deaths in either study arm so not possible to assess risk

Adverse events

Treatment duration 28 ‐ 42 days

see comment

—

360
(1 RCT)

—

single included study reported no adverse events in either study arm so not possible to assess risk

Reoperation
Treatment duration 28 ‐ 42 days

see comment

—

—

—

not reported in single included study in this comparison

Wound infection

Treatment duration 28 ‐ 42 days

see comment

—

—

—

not reported in single included study in this comparison

Wound healing

Treatment duration 28 ‐ 42 days

see comment

—

—

—

not reported in single included study in this comparison

*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

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

Total VTE (symptomatic and asymptomatic)

Treatment duration 28 ‐ 42 days

Study population

OR 0.19
(0.11 to 0.33)

1733
(1 RCT)

⊕⊕⊕⊝
MODERATE ¹

—

86 per 1000

18 per 1000
(10 to 30)

Asymptomatic DVT

Treatment duration 28 ‐ 42 days

see comment

—

—

—

not reported in single included study in this comparison

Asymptomatic proximal DVT

Treatment duration 28 ‐ 42 days

see comment

—

—

—

not reported in single included study in this comparison

Asymptomatic distal DVT

Treatment duration 28 ‐ 42 days

see comment

—

—

—

not reported in single included study in this comparison

All‐cause mortality

Treatment duration 28 ‐ 42 days

Study population

OR 0.33
(0.07 to 1.66)

1733
(1 RCT)

⊕⊕⊝⊝
LOW ^{1 2}

—

7 per 1000

2 per 1000
(0 to 11)

Adverse events

Treatment duration 28 ‐ 42 days

Study population

OR 0.87
(0.74 to 1.03)

2457
(1 RCT)

⊕⊕⊕⊝
MODERATE ¹

—

657 per 1000

625 per 1000
(586 to 663)

Reoperation
Treatment duration 28 ‐ 42 days

see comment

—

2457
(1 RCT)

—

single study reported no cases of reoperation in the study arms

Wound infection

Treatment duration 28 ‐ 42 days

Study population

OR 1.34
(0.46 to 3.86)

2457
(1 RCT)

⊕⊕⊝⊝
LOW ^{1 2}

—

5 per 1000

7 per 1000
(2 to 19)

Wound healing

Treatment duration 28 ‐ 42 days

see comment

—

—

—

not reported in single included study in this comparison

*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

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)

Total VTE (symptomatic and asymptomatic)

Treatment duration 28 ‐ 42 days

Study population

OR 0.26
(0.14 to 0.50)

557
(1 RCT)

⊕⊕⊕⊝
MODERATE ¹

—

158 per 1000

46 per 1000
(26 to 86)

Asymptomatic DVT

Treatment duration 28 ‐ 42 days

Study population

OR 0.26
(0.13 to 0.54)

557
(1 RCT)

⊕⊕⊕⊝
MODERATE ¹

—

125 per 1000

36 per 1000
(18 to 72)

Asymptomatic proximal DVT

Treatment duration 28 ‐ 42 days

see comment

—

—

—

not reported in single included study in this comparison

Asymptomatic distal DVT

Treatment duration 28 ‐ 42 days

Study population

OR 0.26
(0.13 to 0.54)

557
(1 RCT)

⊕⊕⊕⊝
MODERATE ¹

—

125 per 1000

36 per 1000
(18 to 72)

All‐cause mortality

Treatment duration 28 ‐ 42 days

see comment

—

842
(1 RCT)

—

the single included study reported no deaths in either study arm

Adverse events

Treatment duration 28 ‐ 42 days

see comment

—

—

—

not reported in single included study in this comparison

Reoperation
Treatment duration 28 ‐ 42 days

see comment

—

—

—

outcome reported as part of the definition of the outcome major bleeding but data not reported separately

Wound infection

Treatment duration 28 ‐ 42 days

see comment

—

—

—

not reported in single included study in this comparison

Wound healing

Treatment duration 28 ‐ 42 days

see comment

—

—

—

not reported in single included study in this comparison

*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: Ccnfidence 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

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

Total VTE (symptomatic and asymptomatic)

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)

Asymptomatic DVT

Treatment duration 28 ‐ 42 days

see comment

—

—

—

not reported in single included study in this comparison

Asymptomatic proximal DVT

Treatment duration 28 ‐ 42 days

see comment

—

—

—

not reported in single included study in this comparison

Asymptomatic distal DVT

Treatment duration 28 ‐ 42 days

see comment

—

—

—

not reported in single included study in this comparison

All‐cause mortality

Treatment duration 28 ‐ 42 days

see comment

OR 5.07
(0.24 to 105.83)

1279
(1 RCT)

⊕⊕⊝⊝
LOW ^{1 3}

no cases of death reported in the heparin study arm

Adverse events

Treatment duration 28 ‐ 42 days

see comment

—

—

—

not reported in single included study in this comparison

Reoperation
Treatment duration 28 ‐ 42 days

Study population

OR 4.60
(0.99 to 21.38)

1279
(1 RCT)

⊕⊕⊝⊝
LOW ^{1 3}

—

3 per 1000

14 per 1000
(3 to 63)

Wound infection

Treatment duration 28 ‐ 42 days

see comment

—

—

—

not reported in single included study in this comparison

Wound healing

Treatment duration 28 ‐ 42 days

see comment

—

—

—

not reported in single included study in this comparison

*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

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

Total VTE (symptomatic and asymptomatic)

Treatment duration 28 ‐ 42 days

Study population

OR 0.53
(0.29 to 0.97)

12447
(4 RCTs)

⊕⊕⊕⊝
MODERATE ¹

—

41 per 1000

22 per 1000
(12 to 40)

Asymptomatic DVT

Treatment duration 28 ‐ 42 days

Study population

OR 0.56
(0.19 to 1.59)

6559
(2 RCTs)

⊕⊕⊝⊝
LOW ²

—

42 per 1000

24 per 1000
(8 to 65)

Asymptomatic proximal DVT

Treatment duration 28 ‐ 42 days

Study population

OR 0.73
(0.46 to 1.15)

2704
(1 RCT)

⊕⊕⊕⊝
MODERATE ³

—

35 per 1000

26 per 1000
(16 to 40)

Asymptomatic distal DVT

Treatment duration 28 ‐ 42 days

Study population

OR 1.22
(0.75 to 1.99)

2639
(1 RCT)

⊕⊕⊕⊝
MODERATE ³

—

27 per 1000

33 per 1000
(20 to 52)

All‐cause mortality

Treatment duration 28 ‐ 42 days

Study population

OR 1.63
(0.64 to 4.16)

14966
(5 RCTs)

⊕⊕⊕⊝
MODERATE ⁴

—

1 per 1000

1 per 1000
(1 to 4)

Adverse events

Treatment duration 28 ‐ 42 days

Study population

OR 0.96
(0.88 to 1.05)

9908
(3 RCTs)

⊕⊕⊕⊕
HIGH

—

691 per 1000

682 per 1000
(663 to 701)

Reoperation

Treatment duration 28 ‐ 42 days

Study population

OR 1.06
(0.34 to 3.24)

15241
(4 RCTs)

⊕⊕⊕⊝
MODERATE ⁴

—

1 per 1000

1 per 1000
(0 to 2)

Wound infection

Treatment duration 28 ‐ 42 days

Study population

OR 0.89
(0.46 to 1.72)

6446
(2 RCTs)

⊕⊕⊕⊝
MODERATE ⁴

—

6 per 1000

5 per 1000
(3 to 10)

Wound healing

Treatment duration 28 ‐ 42 days

see comment

—

—

—

not reported in five included studies in this comparison

*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