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Study flow diagram. CVC: central venous catheter; LMWH: low‐molecular weight heparin; RCT: randomized controlled trial; UFH: unfractionated heparin; VTE: venous thromboembolism.
Figuras y tablas -
Figure 1

Study flow diagram. CVC: central venous catheter; LMWH: low‐molecular weight heparin; RCT: randomized controlled trial; UFH: unfractionated heparin; VTE: venous thromboembolism.

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Risk of bias graph: review authors' judgments about each risk of bias item presented as percentages across all included studies.
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Figure 2

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

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Risk of bias summary: review authors' judgments about each risk of bias item for each included study.
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Figure 3

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

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Comparison 1 Low‐molecular weight heparin (LMWH) versus unfractionated heparin (UFH), Outcome 1 All‐cause mortality.
Figuras y tablas -
Analysis 1.1

Comparison 1 Low‐molecular weight heparin (LMWH) versus unfractionated heparin (UFH), Outcome 1 All‐cause mortality.

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Comparison 1 Low‐molecular weight heparin (LMWH) versus unfractionated heparin (UFH), Outcome 2 Pulmonary embolism (PE).
Figuras y tablas -
Analysis 1.2

Comparison 1 Low‐molecular weight heparin (LMWH) versus unfractionated heparin (UFH), Outcome 2 Pulmonary embolism (PE).

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Comparison 1 Low‐molecular weight heparin (LMWH) versus unfractionated heparin (UFH), Outcome 3 Symptomatic deep venous thrombosis (DVT).
Figuras y tablas -
Analysis 1.3

Comparison 1 Low‐molecular weight heparin (LMWH) versus unfractionated heparin (UFH), Outcome 3 Symptomatic deep venous thrombosis (DVT).

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Comparison 1 Low‐molecular weight heparin (LMWH) versus unfractionated heparin (UFH), Outcome 4 Asymptomatic DVT.
Figuras y tablas -
Analysis 1.4

Comparison 1 Low‐molecular weight heparin (LMWH) versus unfractionated heparin (UFH), Outcome 4 Asymptomatic DVT.

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Comparison 1 Low‐molecular weight heparin (LMWH) versus unfractionated heparin (UFH), Outcome 5 Major bleeding.
Figuras y tablas -
Analysis 1.5

Comparison 1 Low‐molecular weight heparin (LMWH) versus unfractionated heparin (UFH), Outcome 5 Major bleeding.

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Comparison 1 Low‐molecular weight heparin (LMWH) versus unfractionated heparin (UFH), Outcome 6 Minor bleeding.
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Analysis 1.6

Comparison 1 Low‐molecular weight heparin (LMWH) versus unfractionated heparin (UFH), Outcome 6 Minor bleeding.

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Comparison 1 Low‐molecular weight heparin (LMWH) versus unfractionated heparin (UFH), Outcome 7 Wound hematoma.
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Analysis 1.7

Comparison 1 Low‐molecular weight heparin (LMWH) versus unfractionated heparin (UFH), Outcome 7 Wound hematoma.

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Comparison 1 Low‐molecular weight heparin (LMWH) versus unfractionated heparin (UFH), Outcome 8 Reoperation for bleeding.
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Analysis 1.8

Comparison 1 Low‐molecular weight heparin (LMWH) versus unfractionated heparin (UFH), Outcome 8 Reoperation for bleeding.

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Comparison 1 Low‐molecular weight heparin (LMWH) versus unfractionated heparin (UFH), Outcome 9 Intraoperative transfusion.
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Analysis 1.9

Comparison 1 Low‐molecular weight heparin (LMWH) versus unfractionated heparin (UFH), Outcome 9 Intraoperative transfusion.

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Comparison 1 Low‐molecular weight heparin (LMWH) versus unfractionated heparin (UFH), Outcome 10 Postoperative transfusion.
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Analysis 1.10

Comparison 1 Low‐molecular weight heparin (LMWH) versus unfractionated heparin (UFH), Outcome 10 Postoperative transfusion.

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Comparison 1 Low‐molecular weight heparin (LMWH) versus unfractionated heparin (UFH), Outcome 11 Intraoperative blood loss.
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Analysis 1.11

Comparison 1 Low‐molecular weight heparin (LMWH) versus unfractionated heparin (UFH), Outcome 11 Intraoperative blood loss.

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Comparison 1 Low‐molecular weight heparin (LMWH) versus unfractionated heparin (UFH), Outcome 12 Postoperative drain volume.
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Analysis 1.12

Comparison 1 Low‐molecular weight heparin (LMWH) versus unfractionated heparin (UFH), Outcome 12 Postoperative drain volume.

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Comparison 1 Low‐molecular weight heparin (LMWH) versus unfractionated heparin (UFH), Outcome 13 Thrombocytopenia.
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Analysis 1.13

Comparison 1 Low‐molecular weight heparin (LMWH) versus unfractionated heparin (UFH), Outcome 13 Thrombocytopenia.

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Comparison 2 Low molecular weight heparin (LMWH) versus Fondaparinux, Outcome 1 Any pulmonary embolism.
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Analysis 2.1

Comparison 2 Low molecular weight heparin (LMWH) versus Fondaparinux, Outcome 1 Any pulmonary embolism.

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Comparison 2 Low molecular weight heparin (LMWH) versus Fondaparinux, Outcome 2 Any venous thromboembolism (VTE).
Figuras y tablas -
Analysis 2.2

Comparison 2 Low molecular weight heparin (LMWH) versus Fondaparinux, Outcome 2 Any venous thromboembolism (VTE).

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Comparison 2 Low molecular weight heparin (LMWH) versus Fondaparinux, Outcome 3 Major Bleeding.
Figuras y tablas -
Analysis 2.3

Comparison 2 Low molecular weight heparin (LMWH) versus Fondaparinux, Outcome 3 Major Bleeding.

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Comparison 2 Low molecular weight heparin (LMWH) versus Fondaparinux, Outcome 4 Minor Bleeding.
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Analysis 2.4

Comparison 2 Low molecular weight heparin (LMWH) versus Fondaparinux, Outcome 4 Minor Bleeding.

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Comparison 2 Low molecular weight heparin (LMWH) versus Fondaparinux, Outcome 5 Postoperative drain volume.
Figuras y tablas -
Analysis 2.5

Comparison 2 Low molecular weight heparin (LMWH) versus Fondaparinux, Outcome 5 Postoperative drain volume.

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Comparison 2 Low molecular weight heparin (LMWH) versus Fondaparinux, Outcome 6 Thrombocytopenia.
Figuras y tablas -
Analysis 2.6

Comparison 2 Low molecular weight heparin (LMWH) versus Fondaparinux, Outcome 6 Thrombocytopenia.

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Summary of findings for the main comparison. LMWH prophylaxis compared to UFH prophylaxis in people with cancer without VTE undergoing a surgery

LMWH prophylaxis compared to UFH prophylaxis in people with cancer without VTE undergoing a surgery

Patient or population: People with cancer with perioperative thromboprophylaxis
Settings: Inpatient
Intervention: LMWH
Comparison: UFH

Outcomes

№ of participants
(studies)
Follow up

Certainty of the evidence
(GRADE)

Relative effect
(95% CI)

Anticipated absolute effects* (95% CI)

Risk with UFH prophylaxis

Risk difference with LMWH prophylaxis

Mortality
follow up: range 1 weeks to 3 months

4260
(8 RCTs)

⊕⊕⊕⊝
MODERATE 1

RR 0.82
(0.63 to 1.07)

Study population

51 per 1000

9 fewer per 1000
(19 fewer to 4 more)

Any PE
follow up: range 1 weeks to 3 months

5588
(14 RCTs)

⊕⊕⊕⊝
MODERATE 2

RR 0.49
(0.17 to 1.47)

Study population

6 per 1000

3 fewer per 1000
(5 fewer to 3 more)

Symptomatic DVT
follow up: range 1 weeks to 3 months

2250
(8 RCTs)

⊕⊕⊕⊝
MODERATE 3

RR 0.67
(0.27 to 1.69)

Study population

10 per 1000

3 fewer per 1000
(7 fewer to 7 more)

Symptomatic DVT measured as asymptomatic DVT
follow up: range 1 weeks to 3 months

4938
(12 RCTs)

⊕⊕⊝⊝
LOW 4 5

RR 0.86
(0.71 to 1.05)

Study population

79 per 1000

11 fewer per 1000
(23 fewer to 4 more)

Major bleeding
follow up: range 1 weeks to 3 months

3473
(9 RCTs)

⊕⊕⊕⊝
MODERATE 6

RR 1.01
(0.69 to 1.48)

Study population

31 per 1000

0 fewer per 1000
(10 fewer to 15 more)

Minor bleeding
follow up: range 1 weeks to 3 months

1194
(2 RCTs)

⊕⊕⊕⊝
MODERATE 7

RR 1.01
(0.76 to 1.33)

Study population

142 per 1000

1 more per 1000
(34 fewer to 47 more)

Wound hematoma
follow up: range 1 weeks to 3 months

2827
(6 RCTs)

⊕⊕⊕⊝
MODERATE 8 9

RR 0.70
(0.54 to 0.92)

Study population

86 per 1000

26 fewer per 1000
(39 fewer to 7 fewer)

Reoperation for bleeding
follow up: range 1 weeks to 3 months

1246
(4 RCTs)

⊕⊕⊕⊝
MODERATE 10

RR 0.93
(0.57 to 1.50)

Study population

51 per 1000

4 fewer per 1000
(22 fewer to 26 more)

Intraoperative transfusion
follow up: range 1 weeks to 3 months

737
(2 RCTs)

⊕⊕⊝⊝
LOW 11 12

‐

MD 35.36 lower
(253.19 lower to 182.47 higher)

Postoperative transfusion
follow up: range 1 weeks to 3 months

734
(2 RCTs)

⊕⊕⊝⊝
LOW 13 14

‐

MD 190.03 higher
(23.65 lower to 403.72 higher)

Intraoperative blood loss
follow up: range 1 weeks to 3 months

761
(4 RCTs)

⊕⊕⊕⊝
MODERATE 15

‐

MD 6.75 lower
(85.49 lower to 71.99 higher)

Postoperative drain volume
follow up: range 1 weeks to 3 months

1459
(3 RCTs)

⊕⊕⊕⊝
MODERATE 16

‐

MD 30.18 higher
(36.26 lower to 96.62 higher)

Thrombocytopenia
follow up: range 1 weeks to 3 months

683
(2 RCTs)

⊕⊕⊕⊝
MODERATE 17

RR 3.07
(0.32 to 29.33)

Study population

3 per 1000

6 more per 1000
(2 fewer to 82 more)

*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; RR: Risk ratio; OR: Odds ratio;

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

1 Downgraded due to serious imprecision. 95% CI is consistent with the possibility for important benefit (19 fewer per 1000 absolute reduction) and possibility of no effect (4 more per 1000 absolute increase), including 197 events in total.

2 Downgraded due to serious imprecision. Low event rate, 26 events in total

3 Downgraded due to serious imprecision. Low event rate, 18 events in total

4 Downgraded by one level due to serious inconsistency, outcome measured as surrogate outcome

5 Downgraded due to serious imprecision. 95% CI is consistent with the possibility of important benefit (23 fewer more per 1000 absolute reduction) and possibility of harm (4 more per 1000 increase), including 367 events in total.

6 Downgraded due to serious imprecision. 95% CI is consistent with the possibility of important benefit (10 fewer more per 1000 absolute reduction) and possibility of harm (15 more per 1000 increase), including 107 events in total.

7 Downgraded due to serious imprecision. 95% CI is consistent with the possibility for important benefit (34 fewer per 1000 absolute reduction) and possibility of no effect (47 more per 1000 absolute increase), including 170 events in total.

8 Downgraded due to serious risk of bias; allocation concealment was not clear in 5 out of 6 studies.

9 Downgraded due to serious imprecision. Low event rate, 206 events in total

10 Downgraded due to serious imprecision. 95% CI is consistent with the possibility of benefit (22 fewer per 1000 absolute reduction) and possibility of important harm (26 more per 1000 absolute increase), including 61 events in total.

11 Downgraded due to serious inconsistency. I2= 98%; Dahan 1990 included patients undergoing thoracic surgery for cancer whereas Koppenhagen 1992 included patients undergoing major elective abdominal surgery

12 Downgraded due to serious imprecision. 95% CI is consistent with the possibility for important benefit (253.19 mL less) and possibility of harm (182.47 mL more)

13 Downgraded due to serious inconsistency. I2 = 83%; Dahan 1990 included patients undergoing thoracic surgery for cancer whereas Koppenhagen 1992 included patients undergoing major elective abdominal surgery

14 Downgraded due to serious imprecision. 95% CI is consistent with the possibility for important benefit (23.65mL less) and possibility of harm (40.3.72mL more)

15 Downgraded due to serious imprecision. 95% CI is consistent with the possibility for important benefit (85.49 mL less) and possibility of harm (71.99 mL more)

16 Downgraded due to serious imprecision. 95% CI is consistent with the possibility for important benefit (36.26 mL less) and possibility of harm (96.62 mL more)

17 Downgraded due to serious imprecision. Low event rate, 4 events in total

Figuras y tablas -
Summary of findings for the main comparison. LMWH prophylaxis compared to UFH prophylaxis in people with cancer without VTE undergoing a surgery
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Summary of findings 2. LMWH prophylaxis compared to fondaparinux prophylaxis in people with cancer without VTE undergoing a surgical procedure

LMWH prophylaxis compared to fondaparinux prophylaxis in people with cancer without VTE undergoing a surgical procedure

Patient or population: People with perioperative thromboprophylaxis in people with cancer
Settings: Inpatient
Intervention: LMWH
Comparison: Fondaparinux

Outcomes

№ of participants
(studies)
Follow up

Certainty of the evidence
(GRADE)

Relative effect
(95% CI)

Anticipated absolute effects* (95% CI)

Risk with Fondaparinux prophylaxis

Risk difference with LMWH prophylaxis

Mortality ‐ not reported

‐

‐

‐

‐

‐

Any VTE
follow up: 3 months

1806
(3 RCTs)

⊕⊕⊝⊝
LOW 1 2

RR 2.51
(0.89 to 7.03)

Study population

38 per 1000

57 more per 1000
(4 fewer to 228 more)

Major Bleeding
follow up: 3 months

2339
(3 RCTs)

⊕⊕⊝⊝
LOW 2 4

RR 0.74
(0.45 to 1.23)

Study population

29 per 1000

8 fewer per 1000
(16 fewer to 7 more)

Minor Bleeding

398
(2 RCTs)

⊕⊕⊝⊝
LOW 5 6

RR 0.83
(0.34 to 2.05)

Study population

49 per 1000

8 fewer per 1000
(33 fewer to 52 more)

Thrombocytopenia

282
(1 RCT)

⊕⊕⊝⊝
LOW 7 8

RR 0.35
(0.04 to 3.30)

Study population

21 per 1000

14 fewer per 1000
(20 fewer to 48 more)

Any Pulmonary embolism

116
(1 RCT)

⊕⊕⊝⊝
LOW 9

RR 3.10
(0.13 to 74.64)

Study population

0 per 1000

0 fewer per 1000
(0 fewer to 0 fewer)

Low

1 per 1000

2 more per 1000
(1 fewer to 74 more)

Postoperative drain volume

116
(1 RCT)

⊕⊕⊝⊝
LOW 10

‐

The mean postoperative drain volume was 0 ml

MD 20 ml lower
(114.34 lower to 74.34 higher)

*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; RR: Risk ratio; OR: Odds ratio;

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

1 Downgraded by one level for concerns about both imprecision and indirectness. 95% CI is consistent with the possibility for benefit (4 per 1000 absolute reduction) and possibility of important harm (22 per 1000 absolute increase), including 99 events in total. VTE events included both symptomatic and asymptomatic events for patients with cancer which introduces some level of indirectness.

2 Downgraded by one level due to high risk of bias (lack of allocation concealment and incomplete outcome data in Agnelli 2005; lack of blinding of patients and personnel and incomplete outcome data in Hata 2016 unclear allocation concealment in song 2018)

3 Although the event rate used from the fondaprinux arm includes asymptomatic events, it is very close to rate of symptomatic VTE (3.1%) found in a retrospective cohort Changolkar 2014

4 Downgraded for serious imprecision. 95% CI is consistent with the possibility for important benefit (16 per 1000 absolute reduction) and possibility of important harm (7 per 1000 absolute increase), including 60 events in total.

5 Downgraded for high risk of bias (lack of blinding of patients and personnel and incomplete outcome data in Hata 2016 and unclear allocation concealment in Song 2018)

6 Downgraded for serious imprecision. 95% CI is consistent with the possibility for important benefit (33 per 1000 absolute reduction) and possibility of important harm (52 per 1000 absolute increase), including 18 events in total.

7 Downgraded for high risk of bias (lack of blinding of patients and personnel and incomplete outcome data in Hata 2016)

8 Downgraded for serious imprecision. 95% CI is consistent with the possibility for important benefit (20 per 1000 absolute reduction) and possibility of important harm (48 per 1000 absolute increase), including 4 events in total.

9 Downgraded by two levels for very serious imprecision. 95% CI is consistent with the possibility for important benefit (1 per 1000 absolute reduction) and possibility of important harm (78 per 1000 absolute increase), including 1 event in total.

10 Downgraded due to serious imprecision. 95% CI is consistent with the possibility for important benefit (114.34 mL less) and possibility of harm (74.34 mL more)

Figuras y tablas -
Summary of findings 2. LMWH prophylaxis compared to fondaparinux prophylaxis in people with cancer without VTE undergoing a surgical procedure
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Comparison 1. Low‐molecular weight heparin (LMWH) versus unfractionated heparin (UFH)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 All‐cause mortality Show forest plot

8

4260

Risk Ratio (M‐H, Random, 95% CI)

0.82 [0.63, 1.07]

2 Pulmonary embolism (PE) Show forest plot

14

5588

Risk Ratio (M‐H, Random, 95% CI)

0.49 [0.17, 1.47]

3 Symptomatic deep venous thrombosis (DVT) Show forest plot

8

2250

Risk Ratio (M‐H, Random, 95% CI)

0.67 [0.27, 1.69]

4 Asymptomatic DVT Show forest plot

12

4938

Risk Ratio (M‐H, Random, 95% CI)

0.86 [0.71, 1.05]

5 Major bleeding Show forest plot

9

3473

Risk Ratio (M‐H, Random, 95% CI)

1.01 [0.69, 1.48]

6 Minor bleeding Show forest plot

2

1194

Risk Ratio (M‐H, Random, 95% CI)

1.01 [0.76, 1.33]

7 Wound hematoma Show forest plot

6

2827

Risk Ratio (M‐H, Random, 95% CI)

0.70 [0.54, 0.92]

8 Reoperation for bleeding Show forest plot

4

1246

Risk Ratio (M‐H, Random, 95% CI)

0.93 [0.57, 1.50]

9 Intraoperative transfusion Show forest plot

2

737

Mean Difference (IV, Random, 95% CI)

‐35.36 [‐253.19, 182.47]

10 Postoperative transfusion Show forest plot

2

734

Mean Difference (IV, Random, 95% CI)

190.03 [‐23.65, 403.72]

11 Intraoperative blood loss Show forest plot

4

761

Mean Difference (IV, Random, 95% CI)

‐6.75 [‐85.49, 71.99]

12 Postoperative drain volume Show forest plot

3

1459

Mean Difference (IV, Random, 95% CI)

30.18 [‐36.26, 96.62]

13 Thrombocytopenia Show forest plot

2

683

Risk Ratio (M‐H, Random, 95% CI)

3.07 [0.32, 29.33]
Figuras y tablas -
Comparison 1. Low‐molecular weight heparin (LMWH) versus unfractionated heparin (UFH)
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Comparison 2. Low molecular weight heparin (LMWH) versus Fondaparinux

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Any pulmonary embolism Show forest plot

1

116

Risk Ratio (M‐H, Random, 95% CI)

3.10 [0.13, 74.64]

2 Any venous thromboembolism (VTE) Show forest plot

3

1806

Risk Ratio (M‐H, Random, 95% CI)

2.51 [0.89, 7.03]

3 Major Bleeding Show forest plot

3

2339

Risk Ratio (M‐H, Random, 95% CI)

0.74 [0.45, 1.23]

4 Minor Bleeding Show forest plot

2

398

Risk Ratio (M‐H, Random, 95% CI)

0.83 [0.34, 2.05]

5 Postoperative drain volume Show forest plot

1

116

Mean Difference (IV, Random, 95% CI)

‐20.0 [‐114.34, 74.34]

6 Thrombocytopenia Show forest plot

1

282

Risk Ratio (M‐H, Random, 95% CI)

0.35 [0.04, 3.30]
Figuras y tablas -
Comparison 2. Low molecular weight heparin (LMWH) versus Fondaparinux
Ir a la tabla de la revisión