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Funnel Plot.Inverted funnel plot for studies of warfarin therapy in patients with cancer to improve mortality outcome at 1 year
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Figure 1

Funnel Plot.

Inverted funnel plot for studies of warfarin therapy in patients with cancer to improve mortality outcome at 1 year

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Forest plot of comparison: 1 Warfarin versus no warfarin, outcome: 1.2 Death at 1 year.
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Figure 2

Forest plot of comparison: 1 Warfarin versus no warfarin, outcome: 1.2 Death at 1 year.

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Risk of bias summary for death at 1 year: review authors' judgements about each risk of bias item for each included study.
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Figure 3

Risk of bias summary for death at 1 year: review authors' judgements about each risk of bias item for each included study.

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Risk of bias summary for VTE: review authors' judgements about each risk of bias item for each included study.
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Figure 4

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

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Forest plot of comparison: 1 Warfarin versus no warfarin, outcome: 1.6 Major bleeding.
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Figure 5

Forest plot of comparison: 1 Warfarin versus no warfarin, outcome: 1.6 Major bleeding.

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Risk of bias summary for major bleeding: review authors' judgements about each risk of bias item for each included study.
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Figure 6

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

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Forest plot of comparison: 1 Warfarin versus no warfarin, outcome: 1.5 Minor Bleeding.
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Figure 7

Forest plot of comparison: 1 Warfarin versus no warfarin, outcome: 1.5 Minor Bleeding.

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Risk of bias summary for minor bleeding: review authors' judgements about each risk of bias item for each included study.
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Figure 8

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

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Comparison 1 Warfarin versus no warfarin, Outcome 1 Death at 6 months.
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Analysis 1.1

Comparison 1 Warfarin versus no warfarin, Outcome 1 Death at 6 months.

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Comparison 1 Warfarin versus no warfarin, Outcome 2 Death at 1 year.
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Analysis 1.2

Comparison 1 Warfarin versus no warfarin, Outcome 2 Death at 1 year.

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Comparison 1 Warfarin versus no warfarin, Outcome 3 Death at 2 years.
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Analysis 1.3

Comparison 1 Warfarin versus no warfarin, Outcome 3 Death at 2 years.

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Comparison 1 Warfarin versus no warfarin, Outcome 4 Venous thromboembolism.
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Analysis 1.4

Comparison 1 Warfarin versus no warfarin, Outcome 4 Venous thromboembolism.

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Comparison 1 Warfarin versus no warfarin, Outcome 5 Major bleeding.
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Analysis 1.5

Comparison 1 Warfarin versus no warfarin, Outcome 5 Major bleeding.

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Comparison 1 Warfarin versus no warfarin, Outcome 6 Minor Bleeding.
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Analysis 1.6

Comparison 1 Warfarin versus no warfarin, Outcome 6 Minor Bleeding.

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Comparison 1 Warfarin versus no warfarin, Outcome 7 Death at 5 years.
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Analysis 1.7

Comparison 1 Warfarin versus no warfarin, Outcome 7 Death at 5 years.

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Summary of findings for the main comparison. Oral anticoagulation in patients with cancer with no therapeutic or prophylactic indication for anticoagulation

Oral anticoagulation in patients with cancer with no therapeutic or prophylactic indication for anticoagulation

Patient or population: patients with cancer with no therapeutic or prophylactic indication for anticoagulation.
Settings: Outpatient
Intervention: oral anticoagulation

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Control

oral anticoagulation

Death
Follow‐up: median 1 years

457 per 1000

430 per 1000
(398 to 471)

RR 0.94
(0.87 to 1.03)

1604
(5 studies)

⊕⊕⊕⊝
moderate1

VTE
Follow‐up: 1 years

43 per 1000

6 per 1000
(1 to 52)

RR 0.15
(0.02 to 1.2)

315
(1 study)

⊕⊕⊕⊝
moderate2

Major bleeding
Follow‐up: median 1 years

22 per 1000

93 per 1000
(41 to 213)

RR 4.24
(1.85 to 9.68)

1282
(4 studies)

⊕⊕⊕⊝
moderate3

Minor bleeding
Follow‐up: 1 years

79 per 1000

264 per 1000
(131 to 532)

RR 3.34
(1.66 to 6.74)

851
(3 studies)

⊕⊕⊕⊝
moderate3

Health related quality of life ‐ not reported

See comment

See comment

Not estimable

‐

See comment

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (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;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1 We downgraded because lack of blinding of patients and providers in 4 out of 5 studies; it was unclear whether allocation was concealed in 2 studies; and only one study clearly used intention to treat analysis.
2 We downgraded because the precision of the estimate does not exclude a patient important benefit (the lower limit of RR still suggests a benefit that might be relevant given the high baseline risk).
3 We downgraded because lack of blinding of patients and providers in 3 out of 4 studies; it was unclear whether allocation was concealed in 2 studies; and only one study clearly used intention to treat analysis.

Figuras y tablas -
Summary of findings for the main comparison. Oral anticoagulation in patients with cancer with no therapeutic or prophylactic indication for anticoagulation
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Table 1. Glossary

Term

Meaning

Adjuvant therapy

assisting in the amelioration, or cure of disease

Anticoagulation

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

Antithrombotic

used against or tending to prevent thrombosis (clotting)

Antithrombotic

used against or tending to prevent thrombosis (clotting)

Coagulation

clotting

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

Fibrin

a white insoluble fibrous protein formed from fibrinogen by the action of thrombin especially in the clotting of blood

Fondaparinux

an anticoagulant medication

Haemostatic 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. Two forms of heparin that are used as anticoagulant medications are: unfractionated heparin (UFH) and low molecular weight heparins (LMWH)

Metastasis

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

Oncogene

a gene having the potential to cause a normal cell to become cancerous

Osteoporosis

a condition that affects especially 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 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

Stroma

the supporting framework of an organ typically consisting of connective tissue

Thrombin

a 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 antagonists

anticoagulant medications that are used for anticoagulation. Warfarin is a vitamin K antagonist

Warfarin

an anticoagulant medication that is a vitamin K antagonist that is used for anticoagulation

Ximelagatran

an anticoagulant medication

Major bleeding

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

Minor bleeding

any bleeding not classified as major bleeding
Figuras y tablas -
Table 1. Glossary
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Comparison 1. Warfarin versus no warfarin

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Death at 6 months Show forest plot

4

1293

Risk Ratio (M‐H, Random, 95% CI)

0.96 [0.80, 1.16]

2 Death at 1 year Show forest plot

5

1604

Risk Ratio (M‐H, Random, 95% CI)

0.94 [0.87, 1.03]

3 Death at 2 years Show forest plot

3

875

Risk Ratio (M‐H, Random, 95% CI)

0.97 [0.87, 1.08]

4 Venous thromboembolism Show forest plot

1

315

Risk Ratio (M‐H, Random, 95% CI)

0.15 [0.02, 1.20]

5 Major bleeding Show forest plot

4

1282

Risk Ratio (M‐H, Random, 95% CI)

4.24 [1.85, 9.68]

6 Minor Bleeding Show forest plot

3

851

Risk Ratio (M‐H, Random, 95% CI)

3.34 [1.66, 6.74]

7 Death at 5 years Show forest plot

2

686

Risk Ratio (M‐H, Random, 95% CI)

0.91 [0.83, 1.01]
Figuras y tablas -
Comparison 1. Warfarin versus no warfarin
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