Anticoagulación por vía oral en personas con cáncer en quienes no hay indicación terapéutica o profiláctica de anticoagulantes
Appendices
Appendix 1. Living systematic review protocol
The methods outlined below are specific to maintaining the review as a living systematic review on the Cochrane Library (Synnot 2017). They will be implemented immediately upon publication of this update. Core review methods, such as the criteria for considering studies in the review and assessment of risk of bias, are unchanged. As such, below we outline only those areas of the methods for which additional or different activities are planned or rules apply.
Search methods for identification of studies
We will rerun the majority of searches monthly. For electronic databases and other electronic sources (CENTRAL, MEDLINE, Embase), we have set up auto‐alerts to deliver a monthly search yield by email. We will search the remaining resources (conference proceedings of the American Society of Clinical Oncology (ASCO), the American Society of Haematology (ASH) and clinicaltrials.gov) on a monthly basis. For that purpose, we will note when these conference proceedings are published.
As additional steps to inform the living systematic review, we will contact corresponding authors of ongoing studies as they are identified and ask them to advise when results are available, and to share early or unpublished data. We will contact the corresponding authors of any newly included studies for advice as to other relevant studies. We will conduct citation tracking of included studies in Web of Science Core Collection on an ongoing basis. For that purpose, we have set up citation alerts in Web of Science Core Collection. We will manually screen the reference list of any newly included studies, and identified relevant guidelines and systematic reviews. In addition, we will use the 'related citation' feature in PubMed to identify additional articles.
We will review search methods and strategies approximately yearly, to ensure they reflect any terminology changes in the topic area, or in the databases.
Selection of studies
We will immediately screen any new citations retrieved by the monthly searches. As the first step of monthly screening, we will apply the machine learning classifier (RCT model) available in the Cochrane Register of Studies (CSR‐Web; Wallace 2017). The classifier assigns a probability (from 0 to 100) to each citation for being a true RCT. For citations that are assigned a probability score of less than 10, the machine learning classifier currently has a specificity/recall of 99.987% (Wallace 2017). For citations assigned a score from 10 to 100, we will screen them in duplicate and independently. Citations that score 9 or less will be screened by Cochrane Crowd (Cochrane Crowd). Any citations that are deemed to be potential RCTs by Cochrane Crowd will be returned to the authors for screening.
Data synthesis
Whenever new evidence (studies, data or information) that meets the review inclusion criteria is identified, we will immediately assess risk of bias and extract the data and incorporate it in the synthesis, as appropriate. We will not adjust the meta‐analyses to account for multiple testing given the methods related to frequent updating of meta‐analyses are under development (Simmonds 2017).
Other
We will review the review scope and methods approximately yearly, or more frequently if appropriate, given potential changes in the topic area, or the evidence being included in the review (e.g. additional comparisons, interventions or outcomes or new review methods available).
Appendix 2. Cochrane's living systematic review pilots
Living systematic reviews offer a new approach to review updating in which the review is continually updated, incorporating relevant new evidence as it becomes available (Elliott 2017). Cochrane is exploring the feasibility of preparing and publishing living systematic reviews in a series of pilots (which includes this review). For the Cochrane pilots, searching is being conducted monthly, and new relevant evidence (studies, data or other information) will be incorporated into the review in a timely manner, so that the findings of the review remain current.
For the most up‐to‐date information about the review, the results of the searches and any new evidence being incorporated, readers are encouraged to check the update status information. The update status information will be updated whenever the searches are rerun. The review will be updated with a new citation whenever a new study is found.
Appendix 3. Full search strategies for the electronic databases ‐ update 2010
| Database | Strategy |
|---|---|
| CENTRAL (the Cochrane Library, latest issue) | #1 heparin OR low molecular weight heparin OR LMWH OR low‐molecular‐weight‐heparin OR nadroparin OR fraxiparin OR enoxaparin OR clexane OR lovenox OR dalteparin OR fragmin OR ardeparin OR normiflo OR tinzaparin OR logiparin OR innohep OR certoparin OR sandoparin OR reviparin OR clivarin OR danaproid OR orgaran #6 1 OR 2 OR 3 OR 4 OR 5 |
| MEDLINE | #1 Heparin/ #12 (Pradaxa or Dabigatran or rivaroxaban or Xarelto or apixaban).tw. |
| Embase | #1 Heparin/ #14 (Pradaxa OR Dabigatran OR rivaroxaban OR Xarelto OR apixaban).tw. |
| ISI (International Scientific Information) the Web of Science | #1 heparin OR low molecular weight heparin OR LMWH OR low‐molecular‐weight‐heparin OR nadroparin OR fraxiparin OR enoxaparin OR clexane OR lovenox OR dalteparin OR fragmin OR ardeparin OR normiflo OR tinzaparin OR logiparin OR innohep OR certoparin OR sandoparin OR reviparin OR clivarin OR danaproid OR orgaran # 5 Pradaxa OR Dabigatran OR rivaroxaban OR Xarelto OR apixaban |
Appendix 4. Full search strategies for the electronic databases ‐ update 2013
| Database | Strategy |
|---|---|
| CENTRAL (the Cochrane Library, latest issue) | #1 MeSH descriptor: [Heparin] explode all trees #2 (LMWH or heparin or nadroparin or fraxiparin or enoxaparin or clexane or lovenox or dalteparin or fragmin or ardeparin or normiflo or tinzaparin or logiparin or innohep or certoparin or sandoparin or reviparin or clivarin or danaproid or orgaran or bemiparin or hibor, badyket, semuloparin, parnaparin, fluxum) #3 MeSH descriptor: [Coumarins] explode all trees #4 (warfarin or coumadin or acenocumarol or phenprocumon or 4‐hydroxicoumarins or oral anticoagulant or vitamin K antagonist or VKA) #5 (fondaparinux or arixtra) #6 (ximelagatran or exanta) #7 (pradaxa or dabigatran or rivaroxaban or xarelto or apixaban or eliquis or edoxaban or lixiana or betrixaban or edoxaban or otamixaban) #8 #1 or #2 or #3 or #4 or #5 or #6 or #7 #9 MeSH descriptor: [Neoplasms] explode all trees #10 (malignan* or neoplasm* or cancer* or carcinoma* or adenocarcinoma* or tumour* or tumor*) #11 #9 or #10 #12 #8 and #10 |
| MEDLINE | #1 exp Heparin/ #2 (LMWH or heparin or nadroparin or fraxiparin or enoxaparin or clexane or lovenox or dalteparin or fragmin or ardeparin or normiflo or tinzaparin or logiparin or innohep or certoparin or sandoparin or reviparin or clivarin or danaproid or orgaran or bemiparin or hibor, badyket, semuloparin, parnaparin, fluxum).tw. #3 exp Coumarins/ #4 (warfarin or coumadin or acenocumarol or phenprocumon or 4‐hydroxicoumarins or oral anticoagulant or vitamin K antagonist or VKA).tw. #5 (fondaparinux or arixtra).tw. #6 (ximelagatran or exanta).tw. #7 (pradaxa or dabigatran or rivaroxaban or xarelto or apixaban or eliquis or edoxaban or lixiana or betrixaban or edoxaban or otamixaban).tw. #8 1 or 2 or 3 or 4 or 5 or 6 or 7 #9 exp Neoplasms/ #10 (malignan* or neoplasm* or cancer* or carcinoma* or adenocarcinoma* or tumour* or tumor*).tw. #11 9 or 10 #12 8 and 11 #13 randomized controlled trial.pt. #14 controlled clinical trial.pt. #15 randomized.ab. #16 placebo.ab. #17 drug therapy.fs. #18 randomly.ab. #19 trial.ab. #20 groups.ab. #21 13 or 14 or 15 or 16 or 17 or 18 or 19 or 20 #22 12 and 21 #23 exp animals/ not humans.sh. #24 22 not 23 |
| Embase | #1 heparin/ #2 exp low molecular weight heparin/ #3 (LMWH or heparin or nadroparin or fraxiparin or enoxaparin or clexane or lovenox or dalteparin or fragmin or ardeparin or normiflo or tinzaparin or logiparin or innohep or certoparin or sandoparin or reviparin or clivarin or danaproid or orgaran or bemiparin or hibor, badyket, semuloparin, parnaparin, fluxum).tw. #4 exp coumarin derivative/ #5 (warfarin or coumadin or acenocumarol or phenprocumon or 4‐hydroxicoumarins or oral anticoagulant or vitamin K antagonist or VKA).tw. #6 (fondaparinux or arixtra).tw. #7 (ximelagatran or exanta).tw. #8 (pradaxa or dabigatran or rivaroxaban or xarelto or apixaban or eliquis or edoxaban or lixiana or betrixaban or edoxaban or otamixaban).tw. #9 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 #10 exp neoplasm/ #11 (malignan* or neoplasm* or cancer* or carcinoma* or adenocarcinoma* or tumour* or tumor*).tw. #12 10 or 11 #13 9 and 12 #14 crossover procedure/ #15 double‐blind procedure/ #16 randomized controlled trial/ #17 single‐blind procedure/ #18 random*.mp. #19 factorial*.mp. #20 (crossover* or cross over* or cross‐over*).mp. #21 placebo*.mp. #22 (double* adj blind*).mp. #23 (singl* adj blind*).mp. #24 assign*.mp. #25 allocat*.mp. #26 volunteer*.mp. #27 14 or 15 or 16 or 17 or 18 or 19 or 20 or 21 or 22 or 23 or 24 or 25 or 26 #28 13 and 27 #29 (exp animal/ or nonhuman/ or exp animal experiment/) not human/ #30 28 not 29 |
Appendix 5. Full search strategies for the electronic databases ‐ update 2017
| Database | Strategy |
|---|---|
| CENTRAL (the Cochrane Library, latest issue) | #1 MeSH descriptor: [Anticoagulants] explode all trees #2 (LMWH* or heparin* or nadroparin* or frixiparin* or enoxaparin* or clexane or klexane or lovenox or dalteparin or fragmin or ardeparin* or normiflo or tinzaparin or logiparin or innohep or certoparin or sandoparin or reviparin or clivarin* or danaproid or danaparoid or orgaran or antixarin or bemiparin* or hibor or zibor or ivor or badyket or semuloparin or parnaparin or tedelparin or fluxum or lohepa or lowhepa or parvoparin or seleparin* or tedelgliparin or lomoparan or orgaran or sulodexide or zivor or embolex or xaparin or clivarine or fondaparinux or Arixtra or UFH or Hepalean or Calcilean or Calciparine or Liquaemin or Liquemin or Multiparin or Novoheparin or Eparina or Hep‐lock or Heparinate or Heparinic acid or Panheprin or Hepalean or Heparin Leo or Heparin Lock) #3 FR‐860 or FR 860 or FR860 or PK‐10,169 or PK 10,169 or PK10,169 or PK‐10169 or PK 10169 or PK10169 or EMT‐967 or EMT 967 or EMT967 or EMT‐966 or EMT 966 or EMT966 or CY 216 or CY‐216 or CY216 or LMF CY‐216 or LMF CY 216 or LMF CY216 #4 MeSH descriptor: [Coumarins] explode all trees #5 (4‐Hydroxycoumarin* or warfarin* or acenocoumarol or nicoumalone or sinthrome or Sintrom or phenindione or dicoumarol or coumadin or phenprocoumon or phepromaron or ethyl‐biscoumacetate or phenindione or Diphenadione or Tioclomarol or Racumi or Marcoumar or Marcumar or Falithrom or Jantoven or vitamin K antagonist* or VKA or fluindione or difenacoum or coumatetralyl) #6 (Dermatan Sulfate or (Chondroitin Sulfate adj B) or Dermatan Sulfphate or DS 435 or MF‐701 or OP‐370 or b‐Heparin or Mistral or Venorix) #7 thrombin near inhibitor* #8 factor Xa inhibitor* or antithrombin* or anticoagul* #9 (rivaroxaban or Xarelto or apixaban or Eliquis or dabigatran etexilate or Edoxaban or Savaysa or Betrixaban or ximelagatran or pradaxa or lixiana or exanta or Darexaban or Otamixaban* or Razaxaban or Bivalirudin or Desirudin or Lepirudin or Melagatran or YM 150 or Iprivask or argatrovan or pradax* or Xarelto or BIBR‐953 or BIBR‐953ZW or BAY 59‐7939 or BMS‐562247 or DU‐176 or DU‐176b).mp. #10 MeSH descriptor: [Rivaroxaban] this term only #11 MeSH descriptor: [Dabigatran] this term only #12 target specific oral anticoagulant* or target‐specific oral anticoagulant* or TSOAC* or new oral anticoagulant* or novel oral anticoagulant* or NOAC* or direct‐acting oral anticoagulant* or direct acting oral anticoagulant* or direct oral anticoagulant* or DOAC* #13 #1 or #2 or #3 or #4 or #5 or #6 or #7 or #8 or #9 or #10 or #11 or #12 #14 MeSH descriptor: [Neoplasms] explode all trees #15 malignan* or neoplasm* or cancer* or carcinoma* or adenocarcinoma* or tumour* or tumor* or glioma* or myeloma* or lymphoma* or leukemia* or leukaemia* or epithelioma* or adenoma* #16 #14 or #15 #17 #13 and #16 |
| MEDLINE | RCT search strategy: 1. exp Anticoagulants/ 2. (LMWH* or heparin* or nadroparin* or frixiparin* or enoxaparin* or clexane or klexane or lovenox or dalteparin or fragmin or ardeparin* or normiflo or tinzaparin or logiparin or innohep or certoparin or sandoparin or reviparin or clivarin* or danaproid or danaparoid or orgaran or antixarin or bemiparin* or hibor or zibor or ivor or badyket or semuloparin or parnaparin or tedelparin or fluxum or lohepa or lowhepa or parvoparin or seleparin* or tedelgliparin or lomoparan or orgaran or sulodexide or zivor or embolex or xaparin or clivarine or fondaparinux or Arixtra or UFH or Hepalean or Calcilean or Calciparine or Liquaemin or Liquemin or Multiparin or Novoheparin or Eparina or Hep‐lock or Heparinate or Heparinic acid or Panheprin or Hepalean or Heparin Leo or Heparin Lock).mp. 3. (FR‐860 or FR 860 or FR860 or PK‐10,169 or PK 10,169 or PK10,169 or PK‐10169 or PK 10169 or PK10169 or EMT‐967 or EMT 967 or EMT967 or EMT‐966 or EMT 966 or EMT966 or CY 216 or CY‐216 or CY216 or LMF CY‐216 or LMF CY 216 or LMF CY216).mp. 4. exp Coumarins/ 5. (4‐Hydroxycoumarin* or warfarin* or acenocoumarol or nicoumalone or sinthrome or Sintrom or phenindione or dicoumarol or coumadin or phenprocoumon or phepromaron or ethyl‐biscoumacetate or phenindione or Diphenadione or Tioclomarol or Racumi or Marcoumar or Marcumar or Falithrom or Jantoven or vitamin K antagonist* or VKA or fluindione or difenacoum or coumatetralyl).mp. 6. (Dermatan Sulfate or (Chondroitin Sulfate adj B) or Dermatan Sulfphate or DS 435 or MF‐701 or OP‐370 or b‐Heparin or Mistral or Venorix).mp. 7. (thrombin adj inhibitor*).mp. 8. (factor Xa inhibitor* or antithrombin* or anticoagul*).mp. 9. (rivaroxaban or Xarelto or apixaban or Eliquis or dabigatran etexilate or Edoxaban or Savaysa or Betrixaban or ximelagatran or pradaxa or lixiana or exanta or Darexaban or Otamixaban* or Razaxaban or Bivalirudin or Desirudin or Lepirudin or Melagatran or YM 150 or Iprivask or argatrovan or pradax* or Xarelto or BIBR‐953 or BIBR‐953ZW or BAY 59‐7939 or BMS‐562247 or DU‐176 or DU‐176b).mp. 10. RIVAROXABAN/ 11. DABIGATRAN/ 12. (target specific oral anticoagulant* or target‐specific oral anticoagulant* or TSOAC* or new oral anticoagulant* or novel oral anticoagulant* or NOAC* or direct‐acting oral anticoagulant* or direct acting oral anticoagulant* or direct oral anticoagulant* or DOAC*).ti,ab,kw. 13. 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 or 10 or 11 or 12 14. exp Neoplasms/ 15. (malignan* or neoplasm* or cancer* or carcinoma* or adenocarcinoma* or tumour* or tumor* or glioma* or myeloma* or lymphoma* or leukemia* or leukaemia* or epithelioma* or adenoma*).tw. 16. 14 or 15 17. 13 and 16 18. randomized controlled trial.pt. 19. controlled clinical trial.pt. 20. randomized.ab. 21. placebo.ab. 22. clinical trials as topic.sh. 23. randomly.ab. 24. trial.ti. 25. 18 or 19 or 20 or 21 or 22 or 23 or 24 26. (animals not (humans and animals)).sh. 27. 25 not 26 28. 17 and 27 Systematic Review search strategy: 1. exp Anticoagulants/ 2. (LMWH* or heparin* or nadroparin* or frixiparin* or enoxaparin* or clexane or klexane or lovenox or dalteparin or fragmin or ardeparin* or normiflo or tinzaparin or logiparin or innohep or certoparin or sandoparin or reviparin or clivarin* or danaproid or danaparoid or orgaran or antixarin or bemiparin* or hibor or zibor or ivor or badyket or semuloparin or parnaparin or tedelparin or fluxum or lohepa or lowhepa or parvoparin or seleparin* or tedelgliparin or lomoparan or orgaran or sulodexide or zivor or embolex or xaparin or clivarine or fondaparinux or Arixtra or UFH or Hepalean or Calcilean or Calciparine or Liquaemin or Liquemin or Multiparin or Novoheparin or Eparina or Hep‐lock or Heparinate or Heparinic acid or Panheprin or Hepalean or Heparin Leo or Heparin Lock).mp. 3. (FR‐860 or FR 860 or FR860 or PK‐10,169 or PK 10,169 or PK10,169 or PK‐10169 or PK 10169 or PK10169 or EMT‐967 or EMT 967 or EMT967 or EMT‐966 or EMT 966 or EMT966 or CY 216 or CY‐216 or CY216 or LMF CY‐216 or LMF CY 216 or LMF CY216).mp. 4. exp Coumarins/ 5. (4‐Hydroxycoumarin* or warfarin* or acenocoumarol or nicoumalone or sinthrome or Sintrom or phenindione or dicoumarol or coumadin or phenprocoumon or phepromaron or ethyl‐biscoumacetate or phenindione or Diphenadione or Tioclomarol or Racumi or Marcoumar or Marcumar or Falithrom or Jantoven or vitamin K antagonist* or VKA or fluindione or difenacoum or coumatetralyl).mp. 6. (Dermatan Sulfate or (Chondroitin Sulfate adj B) or Dermatan Sulfphate or DS 435 or MF‐701 or OP‐370 or b‐Heparin or Mistral or Venorix).mp. 7. (thrombin adj inhibitor*).mp. 8. (factor Xa inhibitor* or antithrombin* or anticoagul*).mp. 9. (rivaroxaban or Xarelto or apixaban or Eliquis or dabigatran etexilate or Edoxaban or Savaysa or Betrixaban or ximelagatran or pradaxa or lixiana or exanta or Darexaban or Otamixaban* or Razaxaban or Bivalirudin or Desirudin or Lepirudin or Melagatran or YM 150 or Iprivask or argatrovan or pradax* or Xarelto or BIBR‐953 or BIBR‐953ZW or BAY 59‐7939 or BMS‐562247 or DU‐176 or DU‐176b).mp. 10. RIVAROXABAN/ 11. DABIGATRAN/ 12. (target specific oral anticoagulant* or target‐specific oral anticoagulant* or TSOAC* or new oral anticoagulant* or novel oral anticoagulant* or NOAC* or direct‐acting oral anticoagulant* or direct acting oral anticoagulant* or direct oral anticoagulant* or DOAC*).ti,ab,kw. 13. 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 or 10 or 11 or 12 14. exp Neoplasms/ 15. (malignan* or neoplasm* or cancer* or carcinoma* or adenocarcinoma* or tumour* or tumor* or glioma* or myeloma* or lymphoma* or leukemia* or leukaemia* or epithelioma* or adenoma*).tw. 16. 14 or 15 17. 13 and 16 18. (review or review,tutorial or review, academic).pt. 19. (medline or medlars or embase or pubmed or cochrane).tw,sh. 20. (scisearch or psychinfo or psycinfo).tw,sh. 21. (psychlit or psyclit).tw,sh. 22. cinahl.tw,sh. 23. ((hand adj2 search*) or (manual* adj2 search*)).tw,sh. 24. (electronic database* or bibliographic database* or computeri?ed database* or online database*).tw,sh. 25. (pooling or pooled or mantel haenszel).tw,sh. 26. (peto or dersimonian or der simonian or fixed effect).tw,sh. 27. (retraction of publication or retracted publication).pt. 28. 19 or 20 or 21 or 22 or 23 or 24 or 25 or 26 or 27 29. 18 and 28 30. meta‐analysis.pt. 31. meta‐analysis.sh. 32. (meta‐analys* or meta analys* or metaanalys*).tw,sh. 33. (systematic* adj5 review*).tw,sh. 34. (systematic* adj5 overview*).tw,sh. 35. (quantitativ* adj5 review*).tw,sh. 36. (quantitativ* adj5 overview*).tw,sh. 37. (methodologic* adj5 review*).tw,sh. 38. (methodologic* adj5 overview*).tw,sh. 39. (integrative research review* or research integration).tw. 40. 30 or 31 or 32 or 33 or 34 or 35 or 36 or 37 or 38 or 39 41. 29 or 40 42. 17 and 41 |
| Embase | RCT search strategy: 1. exp anticoagulant agent/ 2. (LMWH* or heparin* or nadroparin* or frixiparin* or enoxaparin* or clexane or klexane or lovenox or dalteparin or fragmin or ardeparin* or normiflo or tinzaparin or logiparin or innohep or certoparin or sandoparin or reviparin or clivarin* or danaproid or danaparoid or orgaran or antixarin or bemiparin* or hibor or zibor or ivor or badyket or semuloparin or parnaparin or tedelparin or fluxum or lohepa or lowhepa or parvoparin or seleparin* or tedelgliparin or lomoparan or orgaran or sulodexide or zivor or embolex or xaparin or clivarine or fondaparinux or Arixtra or UFH or Hepalean or Calcilean or Calciparine or Liquaemin or Liquemin or Multiparin or Novoheparin or Eparina or Hep‐lock or Heparinate or Heparinic acid or Panheprin or Hepalean or Heparin Leo or Heparin Lock).mp. 3. (FR‐860 or FR 860 or FR860 or PK‐10,169 or PK 10,169 or PK10,169 or PK‐10169 or PK 10169 or PK10169 or EMT‐967 or EMT 967 or EMT967 or EMT‐966 or EMT 966 or EMT966 or CY 216 or CY‐216 or CY216 or LMF CY‐216 or LMF CY 216 or LMF CY216).mp. 4. exp coumarin derivative/ 5. (4‐Hydroxycoumarin* or warfarin* or acenocoumarol or nicoumalone or sinthrome or Sintrom or phenindione or dicoumarol or coumadin or phenprocoumon or phepromaron or ethyl‐biscoumacetate or phenindione or Diphenadione or Tioclomarol or Racumi or Marcoumar or Marcumar or Falithrom or Jantoven or vitamin K antagonist* or VKA or fluindione or difenacoum or coumatetralyl).mp. 6. (Dermatan Sulfate or (Chondroitin Sulfate adj B) or Dermatan Sulfphate or DS 435 or MF‐701 or OP‐370 or b‐Heparin or Mistral or Venorix).mp. 7. (thrombin adj inhibitor*).mp. 8. (factor Xa inhibitor* or antithrombin* or anticoagul*).mp. 9. (rivaroxaban or Xarelto or apixaban or Eliquis or dabigatran etexilate or Edoxaban or Savaysa or Betrixaban or ximelagatran or pradaxa or lixiana or exanta or Darexaban or Otamixaban* or Razaxaban or Bivalirudin or Desirudin or Lepirudin or Melagatran or YM 150 or Iprivask or argatrovan or pradax* or Xarelto or BIBR‐953 or BIBR‐953ZW or BAY 59‐7939 or BMS‐562247 or DU‐176 or DU‐176b).mp. 10. rivaroxaban/ 11. dabigatran/ 12. (target specific oral anticoagulant* or target‐specific oral anticoagulant* or TSOAC* or new oral anticoagulant* or novel oral anticoagulant* or NOAC* or direct‐acting oral anticoagulant* or direct acting oral anticoagulant* or direct oral anticoagulant* or DOAC*).ti,ab,kw. 13. 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 or 10 or 11 or 12 14. exp neoplasm/ 15. (malignan* or neoplasm* or cancer* or carcinoma* or adenocarcinoma* or tumour* or tumor* or glioma* or myeloma* or lymphoma* or leukemia* or leukaemia* or epithelioma* or adenoma*).tw. 16. 14 or 15 17. 13 and 16 18. crossover procedure/ 19. double‐blind procedure/ 20. randomized controlled trial/ 21. single‐blind procedure/ 22. random*.mp. 23. factorial*.mp. 24. (crossover* or cross over* or cross‐over*).mp. 25. placebo*.mp. 26. (double* adj blind*).mp. 27. (singl* adj blind*).mp. 28. assign*.mp. 29. allocat*.mp. 30. volunteer*.mp. 31. 18 or 19 or 20 or 21 or 22 or 23 or 24 or 25 or 26 or 27 or 28 or 29 or 30 32. 17 and 31 Systematic Review search strategy: 1. exp anticoagulant agent/ 2. (LMWH* or heparin* or nadroparin* or frixiparin* or enoxaparin* or clexane or klexane or lovenox or dalteparin or fragmin or ardeparin* or normiflo or tinzaparin or logiparin or innohep or certoparin or sandoparin or reviparin or clivarin* or danaproid or danaparoid or orgaran or antixarin or bemiparin* or hibor or zibor or ivor or badyket or semuloparin or parnaparin or tedelparin or fluxum or lohepa or lowhepa or parvoparin or seleparin* or tedelgliparin or lomoparan or orgaran or sulodexide or zivor or embolex or xaparin or clivarine or fondaparinux or Arixtra or UFH or Hepalean or Calcilean or Calciparine or Liquaemin or Liquemin or Multiparin or Novoheparin or Eparina or Hep‐lock or Heparinate or Heparinic acid or Panheprin or Hepalean or Heparin Leo or Heparin Lock).mp. 3. (FR‐860 or FR 860 or FR860 or PK‐10,169 or PK 10,169 or PK10,169 or PK‐10169 or PK 10169 or PK10169 or EMT‐967 or EMT 967 or EMT967 or EMT‐966 or EMT 966 or EMT966 or CY 216 or CY‐216 or CY216 or LMF CY‐216 or LMF CY 216 or LMF CY216).mp. 4. exp coumarin derivative/ 5. (4‐Hydroxycoumarin* or warfarin* or acenocoumarol or nicoumalone or sinthrome or Sintrom or phenindione or dicoumarol or coumadin or phenprocoumon or phepromaron or ethyl‐biscoumacetate or phenindione or Diphenadione or Tioclomarol or Racumi or Marcoumar or Marcumar or Falithrom or Jantoven or vitamin K antagonist* or VKA or fluindione or difenacoum or coumatetralyl).mp. 6. (Dermatan Sulfate or (Chondroitin Sulfate adj B) or Dermatan Sulfphate or DS 435 or MF‐701 or OP‐370 or b‐Heparin or Mistral or Venorix).mp. 7. (thrombin adj inhibitor*).mp. 8. (factor Xa inhibitor* or antithrombin* or anticoagul*).mp. 9. (rivaroxaban or Xarelto or apixaban or Eliquis or dabigatran etexilate or Edoxaban or Savaysa or Betrixaban or ximelagatran or pradaxa or lixiana or exanta or Darexaban or Otamixaban* or Razaxaban or Bivalirudin or Desirudin or Lepirudin or Melagatran or YM 150 or Iprivask or argatrovan or pradax* or Xarelto or BIBR‐953 or BIBR‐953ZW or BAY 59‐7939 or BMS‐562247 or DU‐176 or DU‐176b).mp. 10. rivaroxaban/ 11. dabigatran/ 12. (target specific oral anticoagulant* or target‐specific oral anticoagulant* or TSOAC* or new oral anticoagulant* or novel oral anticoagulant* or NOAC* or direct‐acting oral anticoagulant* or direct acting oral anticoagulant* or direct oral anticoagulant* or DOAC*).ti,ab,kw. 13. 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 or 10 or 11 or 12 14. exp neoplasm/ 15. (malignan* or neoplasm* or cancer* or carcinoma* or adenocarcinoma* or tumour* or tumor* or glioma* or myeloma* or lymphoma* or leukemia* or leukaemia* or epithelioma* or adenoma*).tw. 16. 14 or 15 17. 13 and 16 18. exp review/ 19. (literature adj3 review*).ti,ab. 20. exp meta analysis/ 21. exp "Systematic Review"/ 22. 18 or 19 or 20 or 21 23. (medline or medlars or embase or pubmed or cinahl or amed or psychlit or psyclit or psychinfo or psycinfo or scisearch or cochrane).ti,ab. 24. RETRACTED ARTICLE/ 25. 23 or 24 26. 22 and 25 27. (systematic* adj2 (review* or overview)).ti,ab. 28. (meta?anal* or meta anal* or meta‐anal* or metaanal* or metanal*).ti,ab. 29. 26 or 27 or 28 30. 17 and 29 |
Appendix 6. GRADE evidence profile: VKA versus no prophylaxis
Question: VKA prophylaxis compared to no prophylaxis in ambulatory people with cancer without VTE receiving systemic therapy
| Certainty assessment | № of patients | Effect | Certainty | Importance | ||||||||
| № of studies | Study design | Risk of bias | Inconsistency | Indirectness | Imprecision | Other considerations | VKA prophylaxis | No prophylaxis | Relative | Absolute | ||
| Mortality (follow up: 12 months) | ||||||||||||
| 5 | randomised trials | not serious | not serious | not serious | serious a | none | 355/650 (54.6%) | 362/631 (57.4%) | RR 0.95 | 29 fewer per 1,000 | ⨁⨁⨁◯ | CRITICAL |
| PE (follow up: 12 months) | ||||||||||||
| 1 | randomised trials | not serious | not serious | serious b | very serious c | none | 1/152 (0.7%) | 1/159 (0.6%) | RR 1.05 | 0 fewer per 1,000 | ⨁◯◯◯ | CRITICAL |
| Symptomatic DVT (follow up: 12 months) | ||||||||||||
| 1 | randomised trials | not serious | not serious | not serious d | very serious e | none | 0/152 (0.0%) | 6/159 (3.8%) | RR 0.08 | 35 fewer per 1,000 | ⨁⨁◯◯ | CRITICAL |
| Major bleeding (follow up: 12 months) | ||||||||||||
| 5 | randomised trials | serious f | not serious | not serious | not serious | none | 108/650 (16.6%) | 35/631 (5.5%) | RR 2.93 | 107 more per 1,000 | ⨁⨁⨁◯ | CRITICAL |
| Minor bleeding (follow up: 12 months) | ||||||||||||
| 4 | randomised trials | serious g | not serious | not serious | not serious | none | 110/440 (25.0%) | 33/423 (7.8%) | RR 3.14 | 167 more per 1,000 | ⨁⨁⨁◯ | CRITICAL |
| HRQoL ‐ not reported | ||||||||||||
| ‐ | ‐ | ‐ | ‐ | ‐ | ‐ | ‐ | ‐ | CRITICAL | ||||
CI: confidence interval; DVT: deep vein thrombosis; HRQoL: health‐related quality of life; PE: pulmonary embolism; RR: risk ratio; VKA: vitamin K antagonist; VTE: venous thromboembolism.
Explanations
aDowngraded 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)
bDowngraded 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.
cDowngraded 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.
dLevine 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)
eDowngraded by two levels due to very serious imprecision. Only 6 events among 311 participants.
fDowngraded 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)
gDowngraded 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)
Appendix 7. GRADE evidence profile: DOAC versus no prophylaxis
Question: DOAC prophylaxis compared to no prophylaxis in ambulatory people with cancer without VTE receiving systemic therapy
| Certainty assessment | № of patients | Effect | Certainty | Importance | ||||||||
| № of studies | Study design | Risk of bias | Inconsistency | Indirectness | Imprecision | Other considerations | DOAC prophylaxis | No prophylaxis | Relative | Absolute | ||
| Mortality (follow up: 3 months) | ||||||||||||
| 1 | randomised trials | not serious a | not serious | not serious | very serious b | none | 1/62 (1.6%) | 2/30 (6.7%) | RR 0.24 | 51 fewer per 1,000 | ⨁⨁◯◯ | CRITICAL |
| PE (follow up: 3 months) | ||||||||||||
| 1 | randomised trials | not serious a | not serious | not serious | very serious c | none | 0/62 (0.0%) | 1/30 (3.3%) | RR 0.16 | 28 fewer per 1,000 | ⨁⨁◯◯ | CRITICAL |
| Symptomatic DVT (follow up: 3 months) | ||||||||||||
| 1 | randomised trials | not serious a | not serious | not serious | very serious d | none | 0/62 (0.0%) | 3/30 (10.0%) | RR 0.07 | 93 fewer per 1,000 | ⨁⨁◯◯ | CRITICAL |
| Major bleeding (follow up: 3 months) | ||||||||||||
| 1 | randomised trials | not serious a | not serious | not serious | very serious c | none | 0/62 (0.0%) | 1/30 (3.3%) | RR 0.16 | 28 fewer per 1,000 | ⨁⨁◯◯ | CRITICAL |
| Minor bleeding (follow up: 3 months) | ||||||||||||
| 1 | randomised trials | not serious a | not serious | not serious | very serious e | none | 4/62 (6.5%) | 0.0% | RR 4.43 | 0 fewer per 1,000 | ⨁⨁◯◯ | CRITICAL |
| HRQoL ‐ not reported | ||||||||||||
| ‐ | ‐ | ‐ | ‐ | ‐ | ‐ | ‐ | ‐ | CRITICAL | ||||
CI: confidence interval; DOAC: Direct Oral AntiCoagulant; DVT: deep vein thrombosis; HRQoL: health‐related quality of life; PE: pulmonary embolism; RR: risk ratio; VTE: venous thromboembolism.
Explanations
aConcern due to unclear allocation concealment
bDowngraded 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.
cDowngraded 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.
dDowngraded by two levels due to very serious imprecision: Including only 3 events among 92 participants.
eDowngraded by two levels due to very serious imprecision: Including only 4 events among 92 participants.
Appendix 8. Detailed results of sensitivity analyses
| Outcome | Major bleeding VKA vs no VKA |
|---|---|
| CCA effect estimate | RR 2.93 (95% CI 1.86 to 4.62) |
| Sensitivity analysis | |
| RI 1.5 intervention 1 control | RR 2.86 (95% CI 2.03 to 4.04) |
| RI 2 intervention 1 control | RR 2.83 (95% CI 2.00 to 3.99) |
| RI 3 intervention 1 control | RR 2.77 (95% CI 1.97 to 3.90) |
| RI 5 intervention 1 control | RR 2.70 (95% CI 1.92 to 3.79) |
| Outcome | Minor bleeding VKA vs no VKA |
|---|---|
| CCA effect estimate | RR 3.14 (95% CI 1.85 to 5.32) |
| Sensitivity analysis | |
| RI 1 intervention 1.5 control | RR 3.05 (95% CI 1.90 to 4.91) |
| RI 1 intervention 2 control | RR 3.02 (95% CI 1.91 to 4.80) |
| RI 1 intervention 3 control | RR 2.97 (95% CI 1.92 to 4.61) |
| RI 1 intervention 5 control | RR 2.89 (95% CI 1.96 to 4.27) |
| CCA: complete case analysis; CI: confidence interval; RI: relative incidence; RR: risk ratio; VKA: vitamin K antagonist. | |
Appendix 9. Study eligibility for subgroup analysis
| Study | Lung cancer | Non‐lung cancer | ||||
|---|---|---|---|---|---|---|
| Included people only with lung cancer | Included people with lung and non‐lung cancer AND provided subgroup data for people with lung cancer | Included people with lung and non‐lung cancer AND > 75% of people had lung cancer | Included people only with non‐lung cancer | Included people with lung and non‐lung cancer AND provided subgroup data for people with non‐lung cancer | Included people with lung and non‐lung cancer AND > 75% of people had non‐lung cancer | |
| x | ‐ | ‐ | ‐ | ‐ | ‐ | |
| ‐ | ‐ | ‐ | x | ‐ | ‐ | |
| ‐ | ‐ | ‐ | ‐ | ‐ | x | |
| x | ‐ | ‐ | ‐ | ‐ | ‐ | |
| x | ‐ | ‐ | ‐ | ‐ | ‐ | |
| ‐ | x | ‐ | ‐ | x | ‐ | |
Study flow diagram.
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.
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)
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)
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
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
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)
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)
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
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
Comparison 2: Direct oral anticoagulants (DOAC) versus no DOAC, Outcome 5: Minor bleeding
| 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 | Certainty of the evidence | Relative effect | Anticipated absolute effects* (95% CI) | |
|---|---|---|---|---|---|
| Risk with No prophylaxis | Risk difference with VKA prophylaxis | ||||
| Mortality | 1281 | ⊕⊕⊕⊝ | RR 0.95 | Study population | |
| 574 per 1,000 | 29 fewer per 1,000 | ||||
| PE | 311 | ⊕⊝⊝⊝ | RR 1.05 | Study population | |
| 6 per 1,000 | 0 fewer per 1,000 | ||||
| Symptomatic DVT | 311 | ⊕⊕⊝⊝ | RR 0.08 | Study population | |
| 38 per 1,000 | 35 fewer per 1,000 | ||||
| Major bleeding | 1281 | ⊕⊕⊕⊝ | RR 2.93 | Study population | |
| 55 per 1,000 | 107 more per 1,000 | ||||
| Minor bleeding | 863 | ⊕⊕⊕⊝ | RR 3.14 | Study population | |
| 78 per 1,000 | 167 more per 1,000 | ||||
| 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). | |||||
| GRADE Working Group grades of evidence | |||||
| 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) | |||||
| 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 | Certainty of the evidence | Relative effect | Anticipated absolute effects* (95% CI) | |
|---|---|---|---|---|---|
| Risk with No prophylaxis | Risk difference with DOAC prophylaxis | ||||
| Mortality | 92 | ⊕⊕⊝⊝ | RR 0.24 | Study population | |
| 67 per 1,000 | 51 fewer per 1,000 | ||||
| PE | 92 | ⊕⊕⊝⊝ | RR 0.16 | Study population | |
| 33 per 1,000 | 28 fewer per 1,000 | ||||
| Symptomatic DVT | 92 | ⊕⊕⊝⊝ | RR 0.07 | Study population | |
| 100 per 1,000 | 93 fewer per 1,000 | ||||
| Major bleeding | 92 | ⊕⊕⊝⊝ | RR 0.16 | Study population | |
| 33 per 1,000 | 28 fewer per 1,000 | ||||
| Minor bleeding | 92 | ⊕⊕⊝⊝ | RR 4.43 | Low | |
| 0 per 1,000 | 0 fewer per 1,000 | ||||
| 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). | |||||
| GRADE Working Group grades of evidence | |||||
| 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. | |||||
| 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. |
| 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] |
| 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] |
