Scolaris Content Display Scolaris Content Display

Study flow diagram.

Figures and Tables -
Figure 1

Study flow diagram.

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

Figures and Tables -
Figure 2

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

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

Figures and Tables -
Figure 3

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

Comparison 1: Low molecular weight heparins (LMWH) versus vitamin K antagonists (VKA), Outcome 1: All‐cause mortality (up to 6 months) (main analysis ‐ active cancer)

Figures and Tables -
Analysis 1.1

Comparison 1: Low molecular weight heparins (LMWH) versus vitamin K antagonists (VKA), Outcome 1: All‐cause mortality (up to 6 months) (main analysis ‐ active cancer)

Comparison 1: Low molecular weight heparins (LMWH) versus vitamin K antagonists (VKA), Outcome 2: All‐cause mortality (time‐to‐event)

Figures and Tables -
Analysis 1.2

Comparison 1: Low molecular weight heparins (LMWH) versus vitamin K antagonists (VKA), Outcome 2: All‐cause mortality (time‐to‐event)

Comparison 1: Low molecular weight heparins (LMWH) versus vitamin K antagonists (VKA), Outcome 3: Recurrent venous thromboembolism (up to 6 months) (main analysis ‐ active cancer)

Figures and Tables -
Analysis 1.3

Comparison 1: Low molecular weight heparins (LMWH) versus vitamin K antagonists (VKA), Outcome 3: Recurrent venous thromboembolism (up to 6 months) (main analysis ‐ active cancer)

Comparison 1: Low molecular weight heparins (LMWH) versus vitamin K antagonists (VKA), Outcome 4: Recurrent venous thromboembolism (time‐to‐event)

Figures and Tables -
Analysis 1.4

Comparison 1: Low molecular weight heparins (LMWH) versus vitamin K antagonists (VKA), Outcome 4: Recurrent venous thromboembolism (time‐to‐event)

Comparison 1: Low molecular weight heparins (LMWH) versus vitamin K antagonists (VKA), Outcome 5: Major bleeding (up to 6 months) (main analysis ‐ active cancer)

Figures and Tables -
Analysis 1.5

Comparison 1: Low molecular weight heparins (LMWH) versus vitamin K antagonists (VKA), Outcome 5: Major bleeding (up to 6 months) (main analysis ‐ active cancer)

Comparison 1: Low molecular weight heparins (LMWH) versus vitamin K antagonists (VKA), Outcome 6: Minor bleeding (up to 6 months) (main analysis ‐ active cancer)

Figures and Tables -
Analysis 1.6

Comparison 1: Low molecular weight heparins (LMWH) versus vitamin K antagonists (VKA), Outcome 6: Minor bleeding (up to 6 months) (main analysis ‐ active cancer)

Comparison 1: Low molecular weight heparins (LMWH) versus vitamin K antagonists (VKA), Outcome 7: Thrombocytopenia (up to 6 months) (main analysis‐ active cancer)

Figures and Tables -
Analysis 1.7

Comparison 1: Low molecular weight heparins (LMWH) versus vitamin K antagonists (VKA), Outcome 7: Thrombocytopenia (up to 6 months) (main analysis‐ active cancer)

Comparison 2: Direct oral anticoagulants (DOAC) versus vitamin K antagonists (VKA), Outcome 1: All‐cause mortality (6‐12 months)

Figures and Tables -
Analysis 2.1

Comparison 2: Direct oral anticoagulants (DOAC) versus vitamin K antagonists (VKA), Outcome 1: All‐cause mortality (6‐12 months)

Comparison 2: Direct oral anticoagulants (DOAC) versus vitamin K antagonists (VKA), Outcome 2: Recurrent venous thromboembolism (6‐12 months)

Figures and Tables -
Analysis 2.2

Comparison 2: Direct oral anticoagulants (DOAC) versus vitamin K antagonists (VKA), Outcome 2: Recurrent venous thromboembolism (6‐12 months)

Comparison 2: Direct oral anticoagulants (DOAC) versus vitamin K antagonists (VKA), Outcome 3: Major bleeding (6‐12 months)

Figures and Tables -
Analysis 2.3

Comparison 2: Direct oral anticoagulants (DOAC) versus vitamin K antagonists (VKA), Outcome 3: Major bleeding (6‐12 months)

Comparison 2: Direct oral anticoagulants (DOAC) versus vitamin K antagonists (VKA), Outcome 4: Minor bleeding (6‐12 months)

Figures and Tables -
Analysis 2.4

Comparison 2: Direct oral anticoagulants (DOAC) versus vitamin K antagonists (VKA), Outcome 4: Minor bleeding (6‐12 months)

Comparison 3: Direct oral anticoagulants (DOAC) versus low molecular weight heparins (LMWH), Outcome 1: All‐cause mortality (6 months)

Figures and Tables -
Analysis 3.1

Comparison 3: Direct oral anticoagulants (DOAC) versus low molecular weight heparins (LMWH), Outcome 1: All‐cause mortality (6 months)

Comparison 3: Direct oral anticoagulants (DOAC) versus low molecular weight heparins (LMWH), Outcome 2: Recurrent VTE (6 months)

Figures and Tables -
Analysis 3.2

Comparison 3: Direct oral anticoagulants (DOAC) versus low molecular weight heparins (LMWH), Outcome 2: Recurrent VTE (6 months)

Comparison 3: Direct oral anticoagulants (DOAC) versus low molecular weight heparins (LMWH), Outcome 3: Major bleeding (6 months)

Figures and Tables -
Analysis 3.3

Comparison 3: Direct oral anticoagulants (DOAC) versus low molecular weight heparins (LMWH), Outcome 3: Major bleeding (6 months)

Comparison 3: Direct oral anticoagulants (DOAC) versus low molecular weight heparins (LMWH), Outcome 4: Major GI bleeding (6 months)

Figures and Tables -
Analysis 3.4

Comparison 3: Direct oral anticoagulants (DOAC) versus low molecular weight heparins (LMWH), Outcome 4: Major GI bleeding (6 months)

Comparison 3: Direct oral anticoagulants (DOAC) versus low molecular weight heparins (LMWH), Outcome 5: Major upper GI bleeding (6 months)

Figures and Tables -
Analysis 3.5

Comparison 3: Direct oral anticoagulants (DOAC) versus low molecular weight heparins (LMWH), Outcome 5: Major upper GI bleeding (6 months)

Comparison 3: Direct oral anticoagulants (DOAC) versus low molecular weight heparins (LMWH), Outcome 6: Major lower GI bleeding (6 months)

Figures and Tables -
Analysis 3.6

Comparison 3: Direct oral anticoagulants (DOAC) versus low molecular weight heparins (LMWH), Outcome 6: Major lower GI bleeding (6 months)

Comparison 3: Direct oral anticoagulants (DOAC) versus low molecular weight heparins (LMWH), Outcome 7: Major non‐GI bleeding (6 months)

Figures and Tables -
Analysis 3.7

Comparison 3: Direct oral anticoagulants (DOAC) versus low molecular weight heparins (LMWH), Outcome 7: Major non‐GI bleeding (6 months)

Comparison 3: Direct oral anticoagulants (DOAC) versus low molecular weight heparins (LMWH), Outcome 8: Minor bleeding (6 months)

Figures and Tables -
Analysis 3.8

Comparison 3: Direct oral anticoagulants (DOAC) versus low molecular weight heparins (LMWH), Outcome 8: Minor bleeding (6 months)

Comparison 3: Direct oral anticoagulants (DOAC) versus low molecular weight heparins (LMWH), Outcome 9: Minor GI bleeding (6 months)

Figures and Tables -
Analysis 3.9

Comparison 3: Direct oral anticoagulants (DOAC) versus low molecular weight heparins (LMWH), Outcome 9: Minor GI bleeding (6 months)

Comparison 3: Direct oral anticoagulants (DOAC) versus low molecular weight heparins (LMWH), Outcome 10: Minor upper GI bleeding (6 months)

Figures and Tables -
Analysis 3.10

Comparison 3: Direct oral anticoagulants (DOAC) versus low molecular weight heparins (LMWH), Outcome 10: Minor upper GI bleeding (6 months)

Comparison 3: Direct oral anticoagulants (DOAC) versus low molecular weight heparins (LMWH), Outcome 11: Minor lower GI bleeding (6 months)

Figures and Tables -
Analysis 3.11

Comparison 3: Direct oral anticoagulants (DOAC) versus low molecular weight heparins (LMWH), Outcome 11: Minor lower GI bleeding (6 months)

Comparison 3: Direct oral anticoagulants (DOAC) versus low molecular weight heparins (LMWH), Outcome 12: Minor non‐GI bleeding (6 months)

Figures and Tables -
Analysis 3.12

Comparison 3: Direct oral anticoagulants (DOAC) versus low molecular weight heparins (LMWH), Outcome 12: Minor non‐GI bleeding (6 months)

Comparison 4: Idraparinux versus vitamin K antagonists (VKA), Outcome 1: All‐cause mortality (up to 6 months)

Figures and Tables -
Analysis 4.1

Comparison 4: Idraparinux versus vitamin K antagonists (VKA), Outcome 1: All‐cause mortality (up to 6 months)

Comparison 4: Idraparinux versus vitamin K antagonists (VKA), Outcome 2: Recurrent VTE (up to 6 months)

Figures and Tables -
Analysis 4.2

Comparison 4: Idraparinux versus vitamin K antagonists (VKA), Outcome 2: Recurrent VTE (up to 6 months)

Comparison 4: Idraparinux versus vitamin K antagonists (VKA), Outcome 3: Major bleeding (up to 6 months)

Figures and Tables -
Analysis 4.3

Comparison 4: Idraparinux versus vitamin K antagonists (VKA), Outcome 3: Major bleeding (up to 6 months)

Comparison 4: Idraparinux versus vitamin K antagonists (VKA), Outcome 4: Minor bleeding (up to 6 months)

Figures and Tables -
Analysis 4.4

Comparison 4: Idraparinux versus vitamin K antagonists (VKA), Outcome 4: Minor bleeding (up to 6 months)

Summary of findings 1. Low molecular weight heparin secondary prophylaxis compared to vitamin K antagonist secondary prophylaxis in people with cancer with venous thromboembolism

Low molecular weight heparin secondary prophylaxis compared to vitamin K antagonist secondary prophylaxis in patients with cancer with venous thromboembolism

Population: People with cancer with venous thromboembolism
Setting: Outpatient
Intervention: LMWH secondary prophylaxis
Comparison: VKA secondary prophylaxis

Outcomes

№ of participants
(studies)
Follow up

Certainty of the evidence
(GRADE)

Relative effect
(95% CI)

Anticipated absolute effects* (95% CI)

Risk with VKA secondary prophylaxis

Risk difference with LMWH secondary prophylaxis

All‐cause mortality (main analysis ‐ active cancer)
follow up: 6 months

1712
(4 RCTs)

⊕⊕⊝⊝
LOW 1 2

RR 0.99
(0.88 to 1.12)

Study population

374 per 1,000

4 fewer per 1,000
(45 fewer to 45 more)

All‐cause mortality (time‐to‐event)

1243
(2 RCTs)

⊕⊕⊝⊝
LOW 2 3

HR 0.94
(0.74 to 1.20)

Study population

374 per 1,000

18 fewer per 1,000
(81 fewer to 56 more)

Recurrent venous thromboembolism (main analysis ‐ active cancer)
follow up: 6 months

1712
(4 RCTs)

⊕⊕⊕⊝
MODERATE 1

RR 0.59
(0.44 to 0.80)

Study population

124 per 1,000

51 fewer per 1,000
(69 fewer to 25 fewer)

Recurrent venous thromboembolism (time‐to‐event)

1243
(2 RCTs)

⊕⊕⊕⊝
MODERATE 3

HR 0.49
(0.31 to 0.78)

Study population

124 per 1,000

61 fewer per 1,000
(84 fewer to 26 fewer)

Major bleeding (main analysis ‐ active cancer)
follow up: 6 months

1712
(4 RCTs)

⊕⊕⊝⊝
LOW 1 2 4

RR 1.09
(0.55 to 2.12)

Study population

43 per 1,000

4 more per 1,000
(19 fewer to 48 more)

Minor bleeding (main analysis ‐ active cancer)
follow up: 6 months

1712
(4 RCTs)

⊕⊝⊝⊝
VERY LOW 1 2 5

RR 0.78
(0.47 to 1.27)

Study population

174 per 1,000

38 fewer per 1,000
(92 fewer to 47 more)

Thrombocytopenia (main analysis‐ active cancer)
follow up: 6 months

138
(1 RCT)

⊕⊕⊝⊝
LOW 3 6

RR 0.94
(0.52 to 1.69)

Study population

254 per 1,000

15 fewer per 1,000
(122 fewer to 175 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 by one level due to serious risk of bias (allocation concealment unclear in one study, lack of blinding of participants and personnel in all the four studies, high risk of incomplete outcome data in one study, and high risk of selective reporting in one study).

2 Downgraded by one level due to serious imprecision. Confidence interval includes suggests both potential harm and potential benefit.

3 Some concern with lack of blinding of patients and personnel.

4 Some concern with inconsistency. I2= 46%

5 Downgraded by one level due to serious inconsistency (I2= 78%)

6 Downgraded by two levels due to very serious imprecision. Confidence interval includes suggests both potential harm and potential benefit. Low number of events.

Figures and Tables -
Summary of findings 1. Low molecular weight heparin secondary prophylaxis compared to vitamin K antagonist secondary prophylaxis in people with cancer with venous thromboembolism
Summary of findings 2. Direct oral anticoagulant secondary prophylaxis compared to Vitamin K antagonist secondary prophylaxis in patients with active cancer with venous thromboembolism

Direct oral anticoagulant secondary prophylaxis compared to Vitamin K antagonist secondary prophylaxis in patients with active cancer with venous thromboembolism

Population: patients with active cancer with venous thromboembolism
Setting: Outpatient
Intervention: DOAC secondary prophylaxis
Comparison: VKA secondary prophylaxis

Outcomes

№ of participants
(studies)
Follow up

Certainty of the evidence
(GRADE)

Relative effect
(95% CI)

Anticipated absolute effects* (95% CI)

Risk with Vitamin K antagonist (VKA) secondary prophylaxis

Risk difference with Direct oral anticoagulant (DOAC) secondary prophylaxis

All‐cause mortality
follow up: range 6 months to 12 months

1060
(4 RCTs)

⊕⊕⊝⊝
LOW 1 2

RR 0.94
(0.72 to 1.23)

Study population

171 per 1,000

10 fewer per 1,000
(48 fewer to 39 more)

Recurrent venous thromboembolism
follow up: range 6 months to 12 months

1050
(4 RCTs)

⊕⊕⊝⊝
LOW 1 3

RR 0.63
(0.34 to 1.15)

Study population

49 per 1,000

18 fewer per 1,000
(32 fewer to 7 more)

Major bleeding
follow up: range 6 months to 12 months

1055
(4 RCTs)

⊕⊕⊝⊝
LOW 1 2

RR 0.77
(0.39 to 1.53)

Study population

37 per 1,000

8 fewer per 1,000
(23 fewer to 20 more)

Minor bleeding
follow up: range 6 months to 12 months

1055
(4 RCTs)

⊕⊕⊝⊝
LOW 1 2

RR 0.83
(0.57 to 1.23)

Study population

127 per 1,000

22 fewer per 1,000
(55 fewer to 29 more)

Thrombocytopenia ‐ not reported

Health related quality of life
follow up: range 3 months to 12 months

8485
(1 RCT)

⊕⊕⊕⊝
MODERATE 4

Prins 2014 (EINSTEIN DVT‐PE; n=8485 ): "in the general population of the EINSTEIN studies, patient‐reported satisfaction and quality of life was better in the rivaroxaban‐treated patients than in the group treated with enoxaparin and vitamin K antagonist, although we have not yet examined whether this is the same in patients with active cancer. Hence, it can be expected that quality of life will also be improved with rivaroxaban compared with long‐term injected low molecular‐weight heparin." The tool used was validated measure of treatment satisfaction – the Anti‐Clot Treatment Scale (ACTS))

*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 Some concern with indirectness (study by Schulman et al (RECOVER I‐II) included patients with a diagnosis of cancer within five years before enrollment), however the weight of these studies was low and heterogeneity was very low.

2 Downgraded by two levels due to very serious imprecision. Confidence interval suggests both potential benefit and potential harm.

3 Downgraded by two levels due to very serious imprecision. Confidence interval suggests both potential benefit and potential no effect. Low number of events.

4 Downgraded by one level for serious indirectness. The study by Prins and colleagues (Prins 2014 ( EINSTEIN n=8485)) reports health related quality of life for the whole study population, without providing data for the cancer subgroup

Figures and Tables -
Summary of findings 2. Direct oral anticoagulant secondary prophylaxis compared to Vitamin K antagonist secondary prophylaxis in patients with active cancer with venous thromboembolism
Summary of findings 4. Direct oral anticoagulant secondary prophylaxis compared to Low molecular weight heparin secondary prophylaxis in patients with cancer with venous thromboembolism

Direct oral anticoagulant secondary prophylaxis compared to Low molecular weight heparin secondary prophylaxis in patients with cancer with venous thromboembolism

Patient or population: patients with cancer with venous thromboembolism
Setting: Outpatient
Intervention: DOAC secondary prophylaxis
Comparison: LMWH secondary prophylaxis

Outcomes

№ of participants
(studies)
Follow up

Certainty of the evidence
(GRADE)

Relative effect
(95% CI)

Anticipated absolute effects* (95% CI)

Risk with Low molecular weight heparin (LMWH) secondary prophylaxis

Risk difference with Direct oral anticoagulant (DOAC) secondary prophylaxis

All‐cause mortality
follow up: mean 6 months

2854
(5 RCTs)

⊕⊕⊝⊝
LOW 1 2

RR 0.97
(0.83 to 1.14)

Study population

248 per 1,000

7 fewer per 1,000
(42 fewer to 35 more)

Recurrent VTE
follow up: mean 6 months

2854
(5 RCTs)

⊕⊕⊝⊝
LOW 1 3

RR 0.63
(0.45 to 0.88)

Study population

87 per 1,000

32 fewer per 1,000
(48 fewer to 10 fewer)

Major bleeding
follow up: mean 6 months

2994
(5 RCTs)

⊕⊕⊝⊝
LOW 1 4

RR 1.20
(0.83 to 1.73)

Study population

35 per 1,000

7 more per 1,000
(6 fewer to 25 more)

Major GI bleeding
follow up: mean 6 months

1838
(4 RCTs)

⊕⊕⊝⊝
LOW 1 4

RR 1.16
(0.62 to 2.17)

Study population

20 per 1,000

3 more per 1,000
(8 fewer to 23 more)

Major upper GI bleeding
follow up: mean 6 months

1838
(4 RCTs)

⊕⊝⊝⊝
VERY LOW 1 5

RR 1.18
(0.51 to 2.76)

Study population

11 per 1,000

2 more per 1,000
(5 fewer to 19 more)

Major lower GI bleeding
follow up: mean 6 months

1838
(4 RCTs)

⊕⊝⊝⊝
VERY LOW 1 5

RR 1.10
(0.43 to 2.80)

Study population

9 per 1,000

1 more per 1,000
(5 fewer to 16 more)

Major non‐GI bleeding
follow up: mean 6 months

1838
(4 RCTs)

⊕⊝⊝⊝
VERY LOW 1 6

RR 0.84
(0.42 to 1.68)

Study population

19 per 1,000

3 fewer per 1,000
(11 fewer to 13 more)

Minor bleeding
follow up: mean 6 months

2854
(5 RCTs)

⊕⊕⊕⊝
MODERATE 1

RR 1.58
(1.15 to 2.16)

Study population

67 per 1,000

39 more per 1,000
(10 more to 78 more)

Minor GI bleeding
follow up: mean 6 months

1495
(2 RCTs)

⊕⊝⊝⊝
VERY LOW 6 7 8

RR 1.37
(0.41 to 4.64)

Study population

25 per 1,000

9 more per 1,000
(15 fewer to 92 more)

Minor upper GI bleeding
follow up: mean 6 months

1495
(2 RCTs)

⊕⊝⊝⊝
VERY LOW 6 7 9

RR 1.03
(0.04 to 25.97)

Study population

11 per 1,000

0 fewer per 1,000
(10 fewer to 267 more)

Minor lower GI bleeding
follow up: mean 6 months

1495
(2 RCTs)

⊕⊕⊝⊝
LOW 5 7

RR 1.54
(0.72 to 3.27)

Study population

15 per 1,000

8 more per 1,000
(4 fewer to 33 more)

Minor non‐GI bleeding
follow up: mean 6 months

1495
(2 RCTs)

⊕⊕⊕⊝
MODERATE 7 10

RR 2.37
(1.44 to 3.89)

Study population

31 per 1,000

42 more per 1,000
(14 more to 89 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 by one level due to serious risk of bias. Allocation concealment was not reported in one study, lack of blinding of patients and personnel in all studies, and high risk of bias related to incomplete outcome data.

2 Downgraded by one level due to serious imprecision. Confidence interval suggests both potential benefit and potential harm.

3 Downgraded by one level due to serious imprecision. Confidence interval suggests both potential benefit and potential no effect.

4 Downgraded by one level due to serious imprecision. Confidence interval suggests both potential harm and potential no effect.

5 Downgraded by two levels due to very serious imprecision. Confidence interval suggests both potential harm and potential no effect. Low number of events.

6 Downgraded by two levels due to very serious imprecision. Confidence interval suggests both potential harm and potential benefit. Low number of events.

7 Some concern with risk of bias. Lack of blinding of patients and personnel in both studies.

8 Downgraded by one level due to serious inconsistency (unexplained heterogeneity I2=64%) and due to some concern with risk of bias.

9 Downgraded by two levels due to very serious inconsistency (unexplained heterogeneity I2=74%.) and due to some concern with risk of bias.

10 Downgraded by one level due to serious imprecision. Low number of events.

Figures and Tables -
Summary of findings 4. Direct oral anticoagulant secondary prophylaxis compared to Low molecular weight heparin secondary prophylaxis in patients with cancer with venous thromboembolism
Summary of findings 5. Idraparinux secondary prophylaxis compared to vitamin K antagonist secondary prophylaxis in people with cancer with venous thromboembolism

Idraparinux secondary prophylaxis compared to VKA secondary prophylaxis in people with cancer with VTE

Population: people with cancer with VTE receiving secondary prophylaxis

Setting: outpatient

Intervention: idraparinux prophylaxis

Control: VKA prophylaxis

Outcomes

№ of participants
(studies)

Certainty of the evidence
(GRADE)

Relative effect
(95% CI)

Anticipated absolute effects* (95% CI)

Risk with VKA secondary prophylaxis

Risk difference with idraparinux secondary prophylaxis

All‐cause mortality
follow‐up: mean 6 months

284
(1 RCT)

⊕⊕⊕⊝
Moderatea

RR 1.11
(0.78 to 1.59)

Study population

283 per 1000

31 more per 1000
(62 fewer to 167 more)

Recurrent VTE
follow‐up: mean 6 months

270
(1 RCT)

⊕⊕⊝⊝
Lowb

RR 0.46
(0.16 to 1.32)

Study population

77 per 1000

42 fewer per 1000
(65 fewer to 25 more)

Major bleeding
follow‐up: mean 6 months

270
(1 RCT)

⊕⊕⊝⊝
Lowc

RR 1.11
(0.35 to 3.56)

Study population

38 per 1000

4 more per 1000
(25 fewer to 98 more)

Minor bleeding – not reported

Health‐related quality of life – 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; RCT: randomized controlled trial; RR: risk ratio; VKA: vitamin K antagonist; VTE: venous thromboembolism.

GRADE Working Group grades of evidence
High certainty: we are very confident that the true effect lies close to that of the estimate of the effect.
Moderate‐certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low‐certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect.
Very low‐certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

aDowngraded one level due to serious imprecision, 95% CI was consistent with the possibility for important benefit (62 per 1000 absolute reduction) and possibility of important harm (167 per 1000 absolute increase), included 85 events.

bDowngraded two level due to very serious imprecision, 95% CI was consistent with the possibility of important benefit (65 fewer per 1000) and possibility of important harm (25 more per 1000); included 15 events.

cDowngraded two levels due to very serious imprecision, 95% CI was consistent with the possibility for important benefit (25 per 1000 absolute reduction) and possibility of important harm (98 per 1000 absolute increase), included 11 events.

Figures and Tables -
Summary of findings 5. Idraparinux secondary prophylaxis compared to vitamin K antagonist secondary prophylaxis in people with cancer with venous thromboembolism
Table 1. Glossary

Term

Definition

Adjuvant therapy

A therapy given in addition to the primary treatment to decrease the risk of the cancer recurrence or to assist in the cure.

Anticoagulation

The process of hindering the clotting of blood especially by treatment with an anticoagulant.

Antithrombotic

Used against or tending to prevent thrombosis (clotting)

Coagulation

Clotting

Direct oral anticoagulants (DOAC)

Also known as NOACs are anticoagulant medications that require less monitoring compared to the traditional anticoagulants.

Deep vein thrombosis (DVT)

A condition marked by the formation of a thrombus within a deep vein (as of the leg or pelvis) that may be asymptomatic or be accompanied by symptoms (as swelling and pain) and that is potentially life‐threatening if dislodgment of the thrombus results in pulmonary embolism.

Fondaparinux

An anticoagulant medication

Hemostatic system

The system that shortens the clotting time of blood and stops bleeding.

Heparin

An enzyme occurring especially in the liver and lungs that prolongs the clotting time of blood by preventing the formation of fibrin. 2 forms of heparin that are used as anticoagulant medications are: unfractionated heparin (UFH) and low molecular weight heparins (LMWH).

Impedance plethysmography

A technique that measures the change in blood volume (venous blood volume as well as the pulsation of the arteries) for a specific body segment

Kappa statistic

A measure of degree of nonrandom agreement between observers, measurements of a specific categorical variable, or both.

Metastasis

The spread of a cancer cells from the initial or primary site of disease to another part of the body.

Parenteral nutrition

The practice of feeding a person intravenously, circumventing the gastrointestinal tract.

Pulmonary embolism (PE)

Embolism of a pulmonary artery or one of its branches that is produced by foreign matter and most often a blood clot originating in a vein of the leg or pelvis and that is marked by labored breathing, chest pain, fainting, rapid heart rate, cyanosis, shock and sometimes death.

Thrombocytopenia

Persistent decrease in the number of blood platelets that is often associated with hemorrhagic conditions.

Thrombosis

The formation or presence of a blood clot within a blood vessel.

Vitamin K antagonists

Anticoagulant medications. Warfarin is a vitamin K antagonist.

Warfarin

An anticoagulant medication that is a vitamin K antagonist that is used for anticoagulation.

Figures and Tables -
Table 1. Glossary
Comparison 1. Low molecular weight heparins (LMWH) versus vitamin K antagonists (VKA)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1.1 All‐cause mortality (up to 6 months) (main analysis ‐ active cancer) Show forest plot

4

1712

Risk Ratio (M‐H, Random, 95% CI)

0.99 [0.88, 1.12]

1.2 All‐cause mortality (time‐to‐event) Show forest plot

2

810

HR (IV, Random, 95% CI)

0.94 [0.74, 1.20]

1.3 Recurrent venous thromboembolism (up to 6 months) (main analysis ‐ active cancer) Show forest plot

4

1712

Risk Ratio (M‐H, Random, 95% CI)

0.59 [0.44, 0.80]

1.4 Recurrent venous thromboembolism (time‐to‐event) Show forest plot

2

810

HR (IV, Random, 95% CI)

0.49 [0.31, 0.78]

1.5 Major bleeding (up to 6 months) (main analysis ‐ active cancer) Show forest plot

4

1712

Risk Ratio (M‐H, Random, 95% CI)

1.09 [0.55, 2.12]

1.6 Minor bleeding (up to 6 months) (main analysis ‐ active cancer) Show forest plot

4

1712

Risk Ratio (M‐H, Random, 95% CI)

0.78 [0.47, 1.27]

1.7 Thrombocytopenia (up to 6 months) (main analysis‐ active cancer) Show forest plot

1

138

Risk Ratio (M‐H, Random, 95% CI)

0.94 [0.52, 1.69]

Figures and Tables -
Comparison 1. Low molecular weight heparins (LMWH) versus vitamin K antagonists (VKA)
Comparison 2. Direct oral anticoagulants (DOAC) versus vitamin K antagonists (VKA)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

2.1 All‐cause mortality (6‐12 months) Show forest plot

4

1060

Risk Ratio (M‐H, Random, 95% CI)

0.94 [0.72, 1.23]

2.2 Recurrent venous thromboembolism (6‐12 months) Show forest plot

4

1050

Risk Ratio (M‐H, Random, 95% CI)

0.63 [0.34, 1.15]

2.3 Major bleeding (6‐12 months) Show forest plot

4

1055

Risk Ratio (M‐H, Random, 95% CI)

0.77 [0.39, 1.53]

2.4 Minor bleeding (6‐12 months) Show forest plot

4

1055

Risk Ratio (M‐H, Random, 95% CI)

0.83 [0.57, 1.23]

Figures and Tables -
Comparison 2. Direct oral anticoagulants (DOAC) versus vitamin K antagonists (VKA)
Comparison 3. Direct oral anticoagulants (DOAC) versus low molecular weight heparins (LMWH)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

3.1 All‐cause mortality (6 months) Show forest plot

5

2854

Risk Ratio (M‐H, Random, 95% CI)

0.97 [0.83, 1.14]

3.2 Recurrent VTE (6 months) Show forest plot

5

2854

Risk Ratio (M‐H, Random, 95% CI)

0.63 [0.45, 0.88]

3.3 Major bleeding (6 months) Show forest plot

5

2994

Risk Ratio (M‐H, Random, 95% CI)

1.20 [0.83, 1.73]

3.3.1 GI tract cancer

4

854

Risk Ratio (M‐H, Random, 95% CI)

1.47 [0.76, 2.84]

3.3.2 Non‐GI tract cancer

4

1853

Risk Ratio (M‐H, Random, 95% CI)

1.05 [0.63, 1.73]

3.3.3 GI tract cancer not specified

1

287

Risk Ratio (M‐H, Random, 95% CI)

0.20 [0.01, 4.04]

3.4 Major GI bleeding (6 months) Show forest plot

4

1838

Risk Ratio (M‐H, Random, 95% CI)

1.16 [0.62, 2.17]

3.5 Major upper GI bleeding (6 months) Show forest plot

4

1838

Risk Ratio (M‐H, Random, 95% CI)

1.18 [0.51, 2.76]

3.6 Major lower GI bleeding (6 months) Show forest plot

4

1838

Risk Ratio (M‐H, Random, 95% CI)

1.10 [0.43, 2.80]

3.7 Major non‐GI bleeding (6 months) Show forest plot

4

1838

Risk Ratio (M‐H, Random, 95% CI)

0.84 [0.42, 1.68]

3.8 Minor bleeding (6 months) Show forest plot

5

2854

Risk Ratio (M‐H, Random, 95% CI)

1.58 [1.15, 2.16]

3.9 Minor GI bleeding (6 months) Show forest plot

2

1495

Risk Ratio (M‐H, Random, 95% CI)

1.37 [0.41, 4.64]

3.10 Minor upper GI bleeding (6 months) Show forest plot

2

1495

Risk Ratio (M‐H, Random, 95% CI)

1.03 [0.04, 25.97]

3.11 Minor lower GI bleeding (6 months) Show forest plot

2

1495

Risk Ratio (M‐H, Random, 95% CI)

1.54 [0.72, 3.27]

3.12 Minor non‐GI bleeding (6 months) Show forest plot

2

1495

Risk Ratio (M‐H, Random, 95% CI)

2.37 [1.44, 3.89]

Figures and Tables -
Comparison 3. Direct oral anticoagulants (DOAC) versus low molecular weight heparins (LMWH)
Comparison 4. Idraparinux versus vitamin K antagonists (VKA)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

4.1 All‐cause mortality (up to 6 months) Show forest plot

1

284

Risk Ratio (M‐H, Random, 95% CI)

1.11 [0.78, 1.59]

4.2 Recurrent VTE (up to 6 months) Show forest plot

1

270

Risk Ratio (M‐H, Random, 95% CI)

0.46 [0.16, 1.32]

4.3 Major bleeding (up to 6 months) Show forest plot

1

270

Risk Ratio (M‐H, Random, 95% CI)

1.11 [0.35, 3.56]

4.4 Minor bleeding (up to 6 months) Show forest plot

1

270

Risk Ratio (M‐H, Random, 95% CI)

0.70 [0.30, 1.60]

Figures and Tables -
Comparison 4. Idraparinux versus vitamin K antagonists (VKA)