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: Vitamin K antagonist (VKA) versus no VKA, Outcome 1: Mortality at 6 months: main analysis

Figures and Tables -
Analysis 1.1

Comparison 1: Vitamin K antagonist (VKA) versus no VKA, Outcome 1: Mortality at 6 months: main analysis

Comparison 1: Vitamin K antagonist (VKA) versus no VKA, Outcome 2: Mortality at 6 months: subgroup analysis (lung cancer)

Figures and Tables -
Analysis 1.2

Comparison 1: Vitamin K antagonist (VKA) versus no VKA, Outcome 2: Mortality at 6 months: subgroup analysis (lung cancer)

Comparison 1: Vitamin K antagonist (VKA) versus no VKA, Outcome 3: Mortality at 12 months: main analysis

Figures and Tables -
Analysis 1.3

Comparison 1: Vitamin K antagonist (VKA) versus no VKA, Outcome 3: Mortality at 12 months: main analysis

Comparison 1: Vitamin K antagonist (VKA) versus no VKA, Outcome 4: Mortality at 12 months: subgroup analysis (lung cancer)

Figures and Tables -
Analysis 1.4

Comparison 1: Vitamin K antagonist (VKA) versus no VKA, Outcome 4: Mortality at 12 months: subgroup analysis (lung cancer)

Comparison 1: Vitamin K antagonist (VKA) versus no VKA, Outcome 5: Mortality at 2 years

Figures and Tables -
Analysis 1.5

Comparison 1: Vitamin K antagonist (VKA) versus no VKA, Outcome 5: Mortality at 2 years

Comparison 1: Vitamin K antagonist (VKA) versus no VKA, Outcome 6: Mortality at 5 years

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Analysis 1.6

Comparison 1: Vitamin K antagonist (VKA) versus no VKA, Outcome 6: Mortality at 5 years

Comparison 1: Vitamin K antagonist (VKA) versus no VKA, Outcome 7: Symptomatic deep vein thrombosis

Figures and Tables -
Analysis 1.7

Comparison 1: Vitamin K antagonist (VKA) versus no VKA, Outcome 7: Symptomatic deep vein thrombosis

Comparison 1: Vitamin K antagonist (VKA) versus no VKA, Outcome 8: Pulmonary embolism

Figures and Tables -
Analysis 1.8

Comparison 1: Vitamin K antagonist (VKA) versus no VKA, Outcome 8: Pulmonary embolism

Comparison 1: Vitamin K antagonist (VKA) versus no VKA, Outcome 9: Major bleeding: main analysis

Figures and Tables -
Analysis 1.9

Comparison 1: Vitamin K antagonist (VKA) versus no VKA, Outcome 9: Major bleeding: main analysis

Comparison 1: Vitamin K antagonist (VKA) versus no VKA, Outcome 10: Major bleeding: subgroup analysis (lung cancer)

Figures and Tables -
Analysis 1.10

Comparison 1: Vitamin K antagonist (VKA) versus no VKA, Outcome 10: Major bleeding: subgroup analysis (lung cancer)

Comparison 1: Vitamin K antagonist (VKA) versus no VKA, Outcome 11: Minor bleeding: main analysis

Figures and Tables -
Analysis 1.11

Comparison 1: Vitamin K antagonist (VKA) versus no VKA, Outcome 11: Minor bleeding: main analysis

Comparison 1: Vitamin K antagonist (VKA) versus no VKA, Outcome 12: Minor bleeding: subgroup analysis (lung cancer)

Figures and Tables -
Analysis 1.12

Comparison 1: Vitamin K antagonist (VKA) versus no VKA, Outcome 12: Minor bleeding: subgroup analysis (lung cancer)

Comparison 2: Direct oral anticoagulants (DOAC) versus no DOAC, Outcome 1: Mortality at 3 months

Figures and Tables -
Analysis 2.1

Comparison 2: Direct oral anticoagulants (DOAC) versus no DOAC, Outcome 1: Mortality at 3 months

Comparison 2: Direct oral anticoagulants (DOAC) versus no DOAC, Outcome 2: Symptomatic deep vein thrombosis

Figures and Tables -
Analysis 2.2

Comparison 2: Direct oral anticoagulants (DOAC) versus no DOAC, Outcome 2: Symptomatic deep vein thrombosis

Comparison 2: Direct oral anticoagulants (DOAC) versus no DOAC, Outcome 3: Pulmonary embolism

Figures and Tables -
Analysis 2.3

Comparison 2: Direct oral anticoagulants (DOAC) versus no DOAC, Outcome 3: Pulmonary embolism

Comparison 2: Direct oral anticoagulants (DOAC) versus no DOAC, Outcome 4: Major bleeding

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Analysis 2.4

Comparison 2: Direct oral anticoagulants (DOAC) versus no DOAC, Outcome 4: Major bleeding

Comparison 2: Direct oral anticoagulants (DOAC) versus no DOAC, Outcome 5: Minor bleeding

Figures and Tables -
Analysis 2.5

Comparison 2: Direct oral anticoagulants (DOAC) versus no DOAC, Outcome 5: Minor bleeding

Summary of findings 1. VKA prophylaxis compared to No prophylaxis in ambulatory patients with cancer without VTE receiving systemic therapy

VKA prophylaxis compared to No prophylaxis in ambulatory patients with cancer without VTE receiving systemic therapy

Patient or population: ambulatory people with cancer without VTE receiving systemic therapy

Setting: outpatient

Intervention: VKA prophylaxis

Control: no prophylaxis

Outcomes

№ of participants
(studies)
Follow up

Certainty of the evidence
(GRADE)

Relative effect
(95% CI)

Anticipated absolute effects* (95% CI)

Risk with No prophylaxis

Risk difference with VKA prophylaxis

Mortality
follow up: 12 months

1281
(5 RCTs)

⊕⊕⊕⊝
MODERATE 1

RR 0.95
(0.87 to 1.03)

Study population

574 per 1,000

29 fewer per 1,000
(75 fewer to 17 more)

PE
follow up: 12 months

311
(1 RCT)

⊕⊝⊝⊝
VERY LOW 2 3

RR 1.05
(0.07 to 16.58)

Study population

6 per 1,000

0 fewer per 1,000
(6 fewer to 98 more)

Symptomatic DVT
follow up: 12 months

311
(1 RCT)

⊕⊕⊝⊝
LOW 4 5

RR 0.08
(0.00 to 1.42)

Study population

38 per 1,000

35 fewer per 1,000
(38 fewer to 16 more)

Major bleeding
follow up: 12 months

1281
(5 RCTs)

⊕⊕⊕⊝
MODERATE 6

RR 2.93
(1.86 to 4.62)

Study population

55 per 1,000

107 more per 1,000
(48 more to 201 more)

Minor bleeding
follow up: 12 months

863
(4 RCTs)

⊕⊕⊕⊝
MODERATE 7

RR 3.14
(1.85 to 5.32)

Study population

78 per 1,000

167 more per 1,000
(66 more to 337 more)

HRQoL ‐ 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; HRQoL: health‐related quality of life; PE: pulmonary embolism; RCT: randomized controlled trial; RR: risk ratio; VKA: vitamin K antagonist.

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 concern about both risk of bias (lack of blinding in patients and personnel and unclear allocation concealment in 4 out of 5 studies) and imprecision (95% CI is consistent with the possibility for important benefit (75 per 1000 absolute reduction) and the possibility of important harm (17 per 1000 absolute increase), large event rate)

2 Downgraded by one level due to indirectness. Levine 1994 used fixed dose of VKA instead of adjusted dose which is not representative of the current practice. This study was the only trial that reported on PE and symptomatic DVT.

3 Downgraded by two levels due to very serious imprecision. 95% CI is consistent with the possibility for important benefit (6 per 1000 absolute reduction) and the possibility of important harm (98 per 1000 absolute increase), including only 2 events.

4Levine 1994 used fixed dose of VKA instead of adjusted dose which is not representative of the current practice. This study was the only trial that reported on PE and symptomatic DVT. We do not think that this indirectness has underestimated the effect on symptomatic DVT (RR 0.08)

5 Downgraded by two levels due to very serious imprecision. Only 6 events among 311 participants.

6 Downgraded by one level due to concern about risk of bias (lack of blinding in patients and personnel and unclear allocation concealment in 4 out of 5 studies)

7 Downgraded by one level due to concern about risk of bias (lack of blinding in patients and personnel and unclear allocation concealment in 3 out of 4 studies)

Figures and Tables -
Summary of findings 1. VKA prophylaxis compared to No prophylaxis in ambulatory patients with cancer without VTE receiving systemic therapy
Summary of findings 2. DOAC prophylaxis compared to No prophylaxis in ambulatory patients with cancer without VTE receiving systemic therapy (Q6b‐ Oral)

DOAC prophylaxis compared to No prophylaxis in ambulatory patients with cancer without VTE receiving systemic therapy

Patient or population: ambulatory people with cancer without VTE receiving systemic therapy

Setting: outpatient

Intervention: DOAC prophylaxis

Control: no prophylaxis

Outcomes

№ of participants
(studies)
Follow up

Certainty of the evidence
(GRADE)

Relative effect
(95% CI)

Anticipated absolute effects* (95% CI)

Risk with No prophylaxis

Risk difference with DOAC prophylaxis

Mortality
follow up: 3 months

92
(1 RCT)

⊕⊕⊝⊝
LOW 1 2

RR 0.24
(0.02 to 2.56)

Study population

67 per 1,000

51 fewer per 1,000
(65 fewer to 104 more)

PE
follow up: 3 months

92
(1 RCT)

⊕⊕⊝⊝
LOW 1 3

RR 0.16
(0.01 to 3.91)

Study population

33 per 1,000

28 fewer per 1,000
(33 fewer to 97 more)

Symptomatic DVT
follow up: 3 months

92
(1 RCT)

⊕⊕⊝⊝
LOW 1 4

RR 0.07
(0.00 to 1.32)

Study population

100 per 1,000

93 fewer per 1,000
(100 fewer to 32 more)

Major bleeding
follow up: 3 months

92
(1 RCT)

⊕⊕⊝⊝
LOW 1 3

RR 0.16
(0.01 to 3.91)

Study population

33 per 1,000

28 fewer per 1,000
(33 fewer to 97 more)

Minor bleeding
follow up: 3 months

92
(1 RCT)

⊕⊕⊝⊝
LOW 1 5

RR 4.43
(0.25 to 79.68)

Low

0 per 1,000

0 fewer per 1,000
(0 fewer to 8 more)

HRQoL ‐ 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; DOAC: direct oral anticoagulant; DVT: deep vein thrombosis; HRQoL: health‐related quality of life; PE: pulmonary embolism; RCT: randomized controlled trial; RR: risk 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 Concern due to unclear allocation concealment

2 Downgraded by two levels due to very serious imprecision: 95% CI is consistent with the possibility for important benefit (65 per 1000 absolute reduction) and the possibility of important harm (104 per 1000 absolute increase), including only 3 events among 92 participants.

3 Downgraded by two levels due to very serious imprecision: 95% CI is consistent with the possibility for important benefit (33 per 1000 absolute reduction) and the possibility of important harm (97 per 1000 absolute increase), including only 1 events among 92 participants.

4 Downgraded by two levels due to very serious imprecision: Including only 3 events among 92 participants.

5 Downgraded by two levels due to very serious imprecision: Including only 4 events among 92 participants.

Figures and Tables -
Summary of findings 2. DOAC prophylaxis compared to No prophylaxis in ambulatory patients with cancer without VTE receiving systemic therapy (Q6b‐ Oral)
Table 1. Glossary

Term

Meaning

Adjuvant therapy

Assisting in the amelioration or cure of disease.

Anticoagulation

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

Antithrombotic

Used against or tending to prevent thrombosis (clotting).

Apixaban

Oral direct factor Xa inhibitor used for anticoagulation.

Coagulation

Clotting.

Direct factor Xa inhibitor

Anticoagulant medications used for anticoagulation. Apixaban is an oral direct factor Xa inhibitor.

Deep vein thrombosis (DVT)

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

Fibrin

White insoluble fibrous protein formed from fibrinogen by the action of thrombin especially in the clotting of blood.

Fondaparinux

An anticoagulant medication.

Hemostatic system

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

Heparin

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).

Major bleeding

Bleeding that is intracranial or retroperitoneal, if it leads directly to death, or if results in hospitalization or transfusion.

Metastasis

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

Minor bleeding

Any bleeding not classified as major bleeding.

Oncogene

Gene having the potential to cause a normal cell to become cancerous.

Osteoporosis

Condition that affects mainly older women and is characterized by decrease in bone mass with decreased density and enlargement of bone spaces producing porosity and brittleness.

Pulmonary embolism (PE)

Embolism of a pulmonary artery or 1 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.

Stroma

The supporting framework of an organ typically consisting of connective tissue.

Thrombin

Proteolytic enzyme formed from prothrombin that facilitates the clotting of blood by catalyzing conversion of fibrinogen to fibrin.

Thrombocytopenia

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

Vitamin K antagonist (VKA)

Anticoagulant medications. Warfarin is a vitamin K antagonist.

Warfarin

Anticoagulant medication that is a vitamin K antagonist.

Ximelagatran

Anticoagulant medication.

Figures and Tables -
Table 1. Glossary
Comparison 1. Vitamin K antagonist (VKA) versus no VKA

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1.1 Mortality at 6 months: main analysis Show forest plot

3

946

Risk Ratio (M‐H, Random, 95% CI)

0.93 [0.77, 1.13]

1.2 Mortality at 6 months: subgroup analysis (lung cancer) Show forest plot

3

946

Risk Ratio (M‐H, Random, 95% CI)

0.93 [0.77, 1.14]

1.2.1 Lung cancer (small cell and non‐small cell)

3

813

Risk Ratio (M‐H, Random, 95% CI)

0.87 [0.72, 1.06]

1.2.2 Non‐lung cancer

1

133

Risk Ratio (M‐H, Random, 95% CI)

1.22 [0.82, 1.82]

1.3 Mortality at 12 months: main analysis Show forest plot

5

1281

Risk Ratio (M‐H, Random, 95% CI)

0.95 [0.87, 1.03]

1.4 Mortality at 12 months: subgroup analysis (lung cancer) Show forest plot

5

1281

Risk Ratio (M‐H, Random, 95% CI)

0.95 [0.87, 1.03]

1.4.1 Lung cancer (small cell and non‐small cell)

4

837

Risk Ratio (M‐H, Random, 95% CI)

0.95 [0.85, 1.05]

1.4.2 Non‐lung cancer

2

444

Risk Ratio (M‐H, Random, 95% CI)

0.95 [0.81, 1.10]

1.5 Mortality at 2 years Show forest plot

2

528

Risk Ratio (M‐H, Random, 95% CI)

0.95 [0.70, 1.30]

1.6 Mortality at 5 years Show forest plot

1

344

Risk Ratio (M‐H, Random, 95% CI)

0.93 [0.83, 1.03]

1.7 Symptomatic deep vein thrombosis Show forest plot

1

311

Risk Ratio (M‐H, Random, 95% CI)

0.08 [0.00, 1.42]

1.8 Pulmonary embolism Show forest plot

1

311

Risk Ratio (M‐H, Random, 95% CI)

1.05 [0.07, 16.58]

1.9 Major bleeding: main analysis Show forest plot

5

1281

Risk Ratio (M‐H, Random, 95% CI)

2.93 [1.86, 4.62]

1.10 Major bleeding: subgroup analysis (lung cancer) Show forest plot

5

1281

Risk Ratio (M‐H, Random, 95% CI)

2.85 [1.76, 4.62]

1.10.1 Lung cancer (small cell and non‐small cell)

4

837

Risk Ratio (M‐H, Random, 95% CI)

3.95 [2.38, 6.55]

1.10.2 Non‐lung cancer

2

444

Risk Ratio (M‐H, Random, 95% CI)

1.75 [0.63, 4.89]

1.11 Minor bleeding: main analysis Show forest plot

4

863

Risk Ratio (M‐H, Random, 95% CI)

3.14 [1.85, 5.32]

1.12 Minor bleeding: subgroup analysis (lung cancer) Show forest plot

4

865

Risk Ratio (M‐H, Random, 95% CI)

3.19 [1.83, 5.55]

1.12.1 Lung cancer (small cell and non‐small cell)

3

554

Risk Ratio (M‐H, Random, 95% CI)

3.79 [1.55, 9.24]

1.12.2 Non‐lung cancer

1

311

Risk Ratio (M‐H, Random, 95% CI)

2.44 [0.64, 9.27]

Figures and Tables -
Comparison 1. Vitamin K antagonist (VKA) versus no VKA
Comparison 2. Direct oral anticoagulants (DOAC) versus no DOAC

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

2.1 Mortality at 3 months Show forest plot

1

92

Risk Ratio (M‐H, Random, 95% CI)

0.24 [0.02, 2.56]

2.2 Symptomatic deep vein thrombosis Show forest plot

1

92

Risk Ratio (M‐H, Random, 95% CI)

0.07 [0.00, 1.32]

2.3 Pulmonary embolism Show forest plot

1

92

Risk Ratio (M‐H, Random, 95% CI)

0.16 [0.01, 3.91]

2.4 Major bleeding Show forest plot

1

92

Risk Ratio (M‐H, Random, 95% CI)

0.16 [0.01, 3.91]

2.5 Minor bleeding Show forest plot

1

92

Risk Ratio (M‐H, Random, 95% CI)

4.43 [0.25, 79.68]

Figures and Tables -
Comparison 2. Direct oral anticoagulants (DOAC) versus no DOAC