Parenteral anticoagulation in ambulatory patients with cancer
Información
- DOI:
- https://doi.org/10.1002/14651858.CD006652.pub5Copiar DOI
- Base de datos:
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- Cochrane Database of Systematic Reviews
- Versión publicada:
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- 11 septiembre 2017see what's new
- Tipo:
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- Intervention
- Etapa:
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- Review
- Grupo Editorial Cochrane:
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Grupo Cochrane de Cáncer ginecológico, neurooncología y otros cánceres
- Copyright:
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- Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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Autores
Contributions of authors
EAA: protocol development, data analysis, manuscript drafting, methodological expertise, review co‐ordination. LAK: searching for trials, screening, data extraction, data analysis, manuscript drafting, review co‐ordination. MH: screening, full‐text retrieval, data extraction, manuscript drafting. CM: screening, full‐text retrieval, data extraction. MB: screening, full‐text retrieval, data extraction. FS: screening, full‐text retrieval, data extraction. IT: screening, full‐text retrieval, data extraction.VY: screening, full‐text retrieval, data extraction. AS: methodological expertise related to the living systematic review approach. HJS: protocol development, data interpretation, methodological expertise.
Sources of support
Internal sources
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No sources of support provided
External sources
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NIHR Cochrane Review Incentive Scheme 2016. Award reference Number 16/72/24, UK
This project was supported by the National Institute for Health Research, via Cochrane Review Incentive Scheme Funding. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the Systematic Reviews Programme, NIHR, NHS or the Department of Health.
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Cochrane Gamechanger Grant, UK
Anneliese Synnot's position is supported by funding through Cochrane's Gamechanger grant
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National Health and Medical Research Council (Partnership Project grant APP1114605), Australia
Anneliese Synnot's position is supported by funding through Australia's National Health and Medical Research Council.
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American Society of Hematology, USA
This project was supported by the American Society of Hematology
Declarations of interest
HJS: panel member of the ASH VTE in cancer patients, Vice‐Chair of the ASH VTE guidelines and played various leadership roles from 1999 until 2014 with ACCP VTE guidelines. EAA served on the executive committee the ACCP Antithrombotic Therapy Guidelines published in 2016. All other co‐authors declare no conflicts of interests.
Acknowledgements
We thank Ms. Ann Grifasi for her administrative support. We thank Dr. Loprinzi and Dr. Paul Novotny of the Mayo Clinic for supplying additional data relating to the study Sideras 2006. We also thank Dr. Lebeau, Dr. Altinbas and Dr. Pelzer for supplying additional data. We thank Rami A Ballout, Andrew Bryant, Heather Dickinson, Sameer K Gunukula, Saskia Kuipers and Saskia Middeldorp, and, Frederiek F van Doormaal for their contributions to previous versions of this review. We also thank Dr. Assem Khamis for his help with conducting the sensitivity analysis.
We thank Jo Morrison, Co‐ordinating Editor for the Cochrane Gynaecological Neuro‐oncology and Orphan Cancers (CGNOC). We also thank Gail Quinn, Managing Editor of the CGNOC for her exceptional support. We thank Joanne Platt, the Information Specialist of the CGNOC for setting up and managing the monthly alerts.
As described under “Sources of Support” this update was supported in part by the American Society of Hematology to inform ASH guidelines on the topic. We thank the ASH guideline panel for prioritizing questions previously addressed by our review and for critically reviewing our work, including Drs. Pablo Alonso, Waleed Alhazanni, Marc Carrier, Cihan Ay, Marcello DiNisio, Lisa Hicks, Alok Khorana, Andrew Leavitt, Agnes Lee, Gary Lyman, Fergus Macbeth, Rebecca Morgan, Simon Noble, and David Stenehjem and patient representatives Jackie Cook and Elizabeth Sexton. Their input was valuable in validating some of the review related decisions such as eligibility of included studies and the analytical approach.
For our update of these reviews, we followed Cochrane methods using the same eligibility criteria and outcomes used previously. The ASH guidelines group used slightly different methods that generated slightly different results. For example, the ASH guideline panel agreed to prioritize different outcomes; include unpublished data; include abstracts; use different definitions for duration of treatment; and rate certainty of evidence slightly differently for some outcomes, for instance because of imprecision or indirectness. These differences are not described in this publication. Instead, they will be described in the ASH guideline publication.
This project was supported by the National Institute for Health Research, via Cochrane Review Incentive Scheme Funding. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the Systematic Reviews Programme, NIHR, NHS or the Department of Health. Anneliese Synnot's position is funded through Cochrane's Gamechanger Grant and Australia's National Health and Medical Research Council (Partnership Project grant APP1114605).
Version history
| Published | Title | Stage | Authors | Version |
| 2017 Sep 11 | Parenteral anticoagulation in ambulatory patients with cancer | Review | Elie A Akl, Lara A Kahale, Maram B Hakoum, Charbel F Matar, Francesca Sperati, Maddalena Barba, Victor ED Yosuico, Irene Terrenato, Anneliese Synnot, Holger Schünemann | |
| 2014 Dec 10 | Parenteral anticoagulation in ambulatory patients with cancer | Review | Elie A Akl, Lara A Kahale, Rami A Ballout, Maddalena Barba, Victor E D Yosuico, Frederiek F van Doormaal, Saskia Middeldorp, Andrew Bryant, Holger Schünemann | |
| 2011 Apr 13 | Parenteral anticoagulation in patients with cancer who have no therapeutic or prophylactic indication for anticoagulation | Review | Elie A Akl, Sameer Gunukula, Maddalena Barba, Victor E D Yosuico, Frederiek F van Doormaal, Saskia Kuipers, Saskia Middeldorp, Heather O Dickinson, Andrew Bryant, Holger Schünemann | |
| 2011 Jan 19 | Parenteral anticoagulation in patients with cancer who have no therapeutic or prophylactic indication for anticoagulation | Review | Elie A Akl, Sameer Gunukula, Maddalena Barba, Victor E D Yosuico, Frederiek F van Doormaal, Saskia Kuipers, Saskia Middeldorp, Heather O Dickinson, Andrew Bryant, Holger Schünemann | |
| 2007 Jul 18 | Parenteral anticoagulation for prolonging survival in patients with cancer who have no other indication for anticoagulation | Review | Elie A Akl, Frederiek F van Doormaal, Maddalena Barba, Ganesh Kamath, Seo Young Kim, Saskia Kuipers, Saskia Middeldorp, Victor E D Yosuico, Heather O Dickinson, Holger Schünemann | |
Differences between protocol and review
This update includes new section relevant to living systematic reviews, which are included in the Methods and also described in Appendix 1.
Keywords
MeSH
Medical Subject Headings (MeSH) Keywords
- Anticoagulants [*administration & dosage, adverse effects];
- Cause of Death;
- Hemorrhage [chemically induced, epidemiology];
- Heparin [*administration & dosage, adverse effects];
- Heparin, Low-Molecular-Weight [administration & dosage];
- Neoplasms [*mortality];
- Quality of Life;
- Randomized Controlled Trials as Topic;
- Survival Analysis;
- Time Factors;
- Venous Thromboembolism [epidemiology, *prevention & control];
- Warfarin [administration & dosage];
Medical Subject Headings Check Words
Humans;
PICO
Study flow diagram.
'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.
Funnel plot of comparison: 1 Heparin versus placebo, outcome: 1.1 Mortality at 12 months‐ Main analysis.
Funnel plot of comparison: 1 Heparin versus placebo, outcome: 1.7 Symptomatic VTE‐ Main analysis.
Comparison 1: Heparin versus placebo, Outcome 1: Mortality at 12 months‐ Main analysis
Comparison 1: Heparin versus placebo, Outcome 2: Mortality at 12 months‐ Subgroups Lung vs non‐Lung Cancer
Comparison 1: Heparin versus placebo, Outcome 3: Mortality at 12 months‐ Subgroups Advanced vs non‐Advanced
Comparison 1: Heparin versus placebo, Outcome 4: Mortality at 24 months‐ Main Analysis
Comparison 1: Heparin versus placebo, Outcome 5: Mortality at 24 months‐ Subgroups Advanced vs non‐Advanced
Comparison 1: Heparin versus placebo, Outcome 6: Mortality over duration of study
Comparison 1: Heparin versus placebo, Outcome 7: Symptomatic VTE‐ Main analysis
Comparison 1: Heparin versus placebo, Outcome 8: Symptomatic VTE‐ Subgroups Lung vs non‐Lung Cancer
Comparison 1: Heparin versus placebo, Outcome 9: PE
Comparison 1: Heparin versus placebo, Outcome 10: Symptomatic DVT
Comparison 1: Heparin versus placebo, Outcome 11: Major bleeding‐ Main analysis
Comparison 1: Heparin versus placebo, Outcome 12: Major bleeding‐ Subgroups Lung vs non‐Lung Cancer
Comparison 1: Heparin versus placebo, Outcome 13: Minor bleeding
Comparison 1: Heparin versus placebo, Outcome 14: Thrombocytopenia
| Heparin prophylaxis compared with no prophylaxis in ambulatory patients with cancer without VTE receiving systemic therapy P: Ambulatory patients with cancer without VTE receiving systemic therapy I: Heparin prophylaxis C: No prophylaxis S: Outpatient | |||||
| Outcomes | № of participants | Quality of the evidence | Relative effect | Anticipated absolute effects* (95% CI) | |
|---|---|---|---|---|---|
| Risk with No prophylaxis | Risk difference with Heparin prophylaxis | ||||
| Mortality | 9575 | ⊕⊕⊕⊝ | RR 0.98 | Study population | |
| 504 per 1000 | 10 fewer per 1000 | ||||
| Mortality | 5229 | ⊕⊕⊕⊝ | RR 0.99 | Study population | |
| 778 per 1000 | 8 fewer per 1000 | ||||
| Symptomatic VTE | 9036 | ⊕⊕⊕⊕ | RR 0.56 | Study population | |
| 68 per 1000 | 30 fewer per 1000 | ||||
| Major bleeding | 9592 | ⊕⊕⊕⊝ | RR 1.30 | Study population | |
| 14 per 1000 | 4 more per 1000 | ||||
| Minor bleeding | 9245 | ⊕⊕⊕⊕ | RR 1.70 | Study population | |
| 24 per 1000 | 17 more per 1000 | ||||
| Thrombocytopenia | 5832 | ⊕⊕⊕⊝ | RR 0.69 | Study population | |
| 105 per 1000 | 33 fewer per 1000 | ||||
| Quality of life impairment | 2241 | ⊕⊕⊕⊝ | ‐ | Macbeth 2016 (FRAGMATIC): " There was no difference between the two groups with respect to quality‐adjusted life years gained in the first year... No difference in overall quality of life at 6 months (P = .94) or at 12 months (P = .89)... Overall quality of life did not change significantly over the study period".Sideras 2006: "The QOL and SDS scores were similar, both at baseline and during the protocol period, in patients randomized to receive LMWH vs those not randomized to receive LMWH." | |
| *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). | |||||
| GRADE Working Group grades of evidence | |||||
| 1 Downgraded one level due to serious imprecision: Confidence interval includes values suggesting clinically significant benefit and values suggesting no effect. 2 Downgraded one level due to serious imprecision: Confidence interval includes values suggesting clinically significant harm and values suggesting no effect. 3 Downgraded one level due to serious imprecision: Confidence interval includes values suggesting clinically significant benefit and values suggesting harm. 4 Downgraded one level due to serious risk of bias: Both studies were open‐label studies (lack of blinding may impact the patient‐reported subjective outcomes) | |||||
| Term | Definition |
|---|---|
| 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) |
| Bacteremia | The presence of bacteria in the blood |
| Central venous line | Synthetic tube that is inserted into a central (large) vein of a patient to provide temporary intravenous access for the administration of fluid, medication or nutrients |
| 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 (such 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 |
| 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. Two 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 statistics | A measure of degree of non‐random agreement between observers and/or measurements of a specific categorical variable |
| Metastasis | The spread of 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 especially affects older women and is characterized by a decrease in bone mass with decreased density and enlargement of bone spaces producing porosity and brittleness |
| Parenteral nutrition | The practice of feeding a patient intravenously, circumventing the gut |
| 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 |
| Thrombosis | The formation or presence of a blood clot within a blood vessel |
| 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, which is used for anticoagulation |
| Ximelagatran | An anticoagulant medication |
| LMWH | Generic name | Prophylactic dose | Therapeutic dose |
|---|---|---|---|
| Lovenox | Enoxaparin | 40 mg once daily | 1 mg/kg twice daily |
| Fragmin | Dalteparin | 2500 to 5000 units once daily | 200 U/kg once daily or |
| Innohep, Logiparin | Tinzaparin | 4500 units once daily | 90 U/kg twice daily |
| Fraxiparine | Nadroparin | 35 to 75 anti‐Xa international units/kg once daily | 175 anti‐Xa int. units/kg once daily |
| Certoparin | Sandoparin | 3000 anti‐Xa international units once daily | — |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1.1 Mortality at 12 months‐ Main analysis Show forest plot | 18 | 9575 | Risk Ratio (M‐H, Random, 95% CI) | 0.98 [0.93, 1.03] |
| 1.2 Mortality at 12 months‐ Subgroups Lung vs non‐Lung Cancer Show forest plot | 12 | 4768 | Risk Ratio (M‐H, Random, 95% CI) | 0.94 [0.86, 1.03] |
| 1.2.1 Lung Cancer (SCLC or NSCLC) | 6 | 3204 | Risk Ratio (M‐H, Random, 95% CI) | 0.89 [0.73, 1.08] |
| 1.2.2 non‐Lung Cancer | 7 | 1564 | Risk Ratio (M‐H, Random, 95% CI) | 0.95 [0.88, 1.03] |
| 1.3 Mortality at 12 months‐ Subgroups Advanced vs non‐Advanced Show forest plot | 18 | 9575 | Risk Ratio (M‐H, Random, 95% CI) | 0.98 [0.94, 1.03] |
| 1.3.1 Advanced cancer | 12 | 6115 | Risk Ratio (M‐H, Random, 95% CI) | 0.98 [0.93, 1.02] |
| 1.3.2 Non‐advanced cancer | 8 | 3460 | Risk Ratio (M‐H, Random, 95% CI) | 0.92 [0.75, 1.12] |
| 1.4 Mortality at 24 months‐ Main Analysis Show forest plot | 14 | 5229 | Risk Ratio (M‐H, Random, 95% CI) | 0.99 [0.96, 1.01] |
| 1.5 Mortality at 24 months‐ Subgroups Advanced vs non‐Advanced Show forest plot | 14 | 5229 | Risk Ratio (M‐H, Random, 95% CI) | 0.99 [0.96, 1.01] |
| 1.5.1 Advanced cancer | 6 | 1554 | Risk Ratio (M‐H, Random, 95% CI) | 0.98 [0.93, 1.03] |
| 1.5.2 Non‐advanced cancer | 8 | 3675 | Risk Ratio (M‐H, Random, 95% CI) | 0.98 [0.93, 1.04] |
| 1.6 Mortality over duration of study Show forest plot | 15 | Hazard Ratio (IV, Random, 95% CI) | 0.93 [0.84, 1.03] | |
| 1.7 Symptomatic VTE‐ Main analysis Show forest plot | 16 | 9036 | Risk Ratio (M‐H, Random, 95% CI) | 0.56 [0.47, 0.68] |
| 1.8 Symptomatic VTE‐ Subgroups Lung vs non‐Lung Cancer Show forest plot | 11 | 8090 | Risk Ratio (M‐H, Random, 95% CI) | 0.52 [0.43, 0.63] |
| 1.8.1 Lung Cancer (SCLC or NSCLC) | 6 | 4217 | Risk Ratio (M‐H, Random, 95% CI) | 0.53 [0.41, 0.68] |
| 1.8.2 Non‐lung cancer | 7 | 3873 | Risk Ratio (M‐H, Random, 95% CI) | 0.51 [0.37, 0.70] |
| 1.9 PE Show forest plot | 14 | 8867 | Risk Ratio (M‐H, Random, 95% CI) | 0.61 [0.47, 0.80] |
| 1.10 Symptomatic DVT Show forest plot | 14 | 8867 | Risk Ratio (M‐H, Random, 95% CI) | 0.46 [0.33, 0.63] |
| 1.11 Major bleeding‐ Main analysis Show forest plot | 18 | 9592 | Risk Ratio (M‐H, Random, 95% CI) | 1.30 [0.94, 1.79] |
| 1.12 Major bleeding‐ Subgroups Lung vs non‐Lung Cancer Show forest plot | 10 | 4163 | Risk Ratio (M‐H, Random, 95% CI) | 1.62 [1.02, 2.56] |
| 1.12.1 Lung Cancer (SCLC or NSCLC) | 5 | 3035 | Risk Ratio (M‐H, Random, 95% CI) | 1.45 [0.77, 2.73] |
| 1.12.2 Non‐lung cancer | 5 | 1128 | Risk Ratio (M‐H, Random, 95% CI) | 1.84 [0.94, 3.58] |
| 1.13 Minor bleeding Show forest plot | 16 | 9245 | Risk Ratio (M‐H, Random, 95% CI) | 1.70 [1.13, 2.55] |
| 1.14 Thrombocytopenia Show forest plot | 12 | 5832 | Risk Ratio (M‐H, Random, 95% CI) | 0.69 [0.37, 1.27] |
