Direct oral anticoagulants vs LMWH for cancer-associated thrombosis - updated evidence on bleeding risk, recurrence and patient-reported outcomes: A systematic review

Table 1 Characteristics of included studies

Ref.	Design	N	Population	Patient characteristics	Intervention	Comparator	Primary outcome	Key findings
Agnelli et al[4], 2020	RCT	1155	Cancer patients with VTE	Active cancer, mixed tumor types	Apixaban 10 mg BID × 7 days, then 5 mg BID	Dalteparin 200 IU/kg daily	Recurrent VTE or major bleeding	Non-inferiority demonstrated; higher bleeding in GI/GU cancers
McBane et al[6], 2020	RCT	300	Active malignancy with VTE	Predominantly solid tumors	Apixaban 10 mg BID × 7 days, then 5 mg BID	Dalteparin 200 IU/kg daily	Major bleeding	Similar efficacy; increased bleeding risk with apixaban
Raskob et al[8], 2018	RCT	1050	Cancer-associated VTE	Mixed cancer types, active disease	Edoxaban 60 mg daily	Dalteparin 200 IU/kg daily	Composite of VTE recurrence or major bleeding	Non-inferiority shown; higher bleeding with edoxaban
Young et al[10], 2018	RCT	406	Cancer patients with VTE	Mixed solid tumors	Rivaroxaban 15 mg BID × 21 days, then 20 mg daily	Dalteparin 200 IU/kg daily	VTE recurrence	Reduced VTE recurrence; increased bleeding risk
Marshall et al[5], 2020	RCT	406	Cancer patients with VTE	12-month follow-up of SELECT-D	Rivaroxaban vs placebo	Dalteparin	VTE recurrence	Sustained VTE reduction; persistent bleeding concern
Planquette et al[7], 2022	RCT	370	Cancer-associated thrombosis	Mixed cancer types	Rivaroxaban 15 mg BID × 21 days, then 20 mg daily	Dalteparin 200 IU/kg daily	Net clinical benefit	Effective VTE prevention; bleeding concerns in GI cancers
Lee et al[29], 2003	RCT	672	Cancer patients with VTE	Mixed cancer types	Dalteparin	Warfarin	VTE recurrence	LMWH superior to warfarin in cancer patients
Lee et al[2], 2015	RCT	900	Active cancer with VTE	Mixed tumor types	Tinzaparin	Warfarin	VTE recurrence	Tinzaparin effective vs warfarin
Schrag et al[9], 2023	RCT	671	Cancer patients with VTE	Real-world population	DOACs (mixed)	LMWH	VTE recurrence	Comparable effectiveness in broader population
Hull et al[27], 2006	RCT	200	Proximal VTE with cancer	Mixed cancer types	Long-term LMWH	Usual care	VTE recurrence	Long-term LMWH beneficial
Deitcher et al[30], 2006	RCT	102	Active cancer with VTE	Mixed solid tumors	Enoxaparin alone	Enoxaparin→Warfarin	VTE recurrence	LMWH alone superior to transition
Riess et al[23], 2015	RCT	200	Cancer patients with VTE	German population	Rivaroxaban	LMWH	Patient satisfaction	Improved satisfaction with rivaroxaban
Di Nisio et al[21], 2019	Post-hoc RCT	1050	Cancer patients with VTE	Extended treatment analysis	Edoxaban	Dalteparin	Extended treatment outcomes	Benefits maintained with extended treatment
Mulder et al[22], 2020	Post-hoc RCT	1050	Different cancer types	Cancer type-specific analysis	Edoxaban	Dalteparin	Cancer type-specific outcomes	Variable outcomes by cancer type
Kraaijpoel et al[24], 2018	Post-hoc RCT	1050	Cancer patients with bleeding	Bleeding impact analysis	Edoxaban	Dalteparin	Clinical impact of bleeding	Bleeding events clinically significant
Coleman et al[13], 2023	Observational	7441	Cancer-associated VTE	Real-world cohort	Rivaroxaban	LMWH	Effectiveness and safety	Comparable real-world effectiveness
Kang et al[14], 2024	Observational	15656	Cancer-associated VTE	Switching patterns analysis	Continuous LMWH vs switch to DOAC	LMWH	Safety of switching	Continuous LMWH safer than switching
Carney et al[16], 2021	Observational	121	Cancer with thrombocytopenia	Thrombocytopenic patients	DOACs	LMWH	Bleeding in thrombocytopenia	Increased bleeding risk in both groups
Weitz et al[15], 2020	Registry	1162	Cancer-associated thrombosis	Global registry data	Variable DOACs	LMWH	Real-world treatment patterns	Geographic variations in treatment
Guo et al[26], 2020	Observational	18223	Cancer-associated thrombosis	US treatment patterns	DOACs	LMWH	Treatment patterns and costs	Economic implications of treatment choice
Farge et al[11], 2018	Observational	365	Cancer patients on LMWH	Quality of life study	LMWH	N/A	Quality of life	Significant QoL burden with LMWH
Schaefer et al[12], 2021	Observational	3139	Cancer-associated thrombosis	Adherence comparison	DOACs	LMWH	Medication adherence	Improved adherence with DOACs
Caroti et al[25], 2023	Observational	2071	Lower bleeding risk CAT	DOAC comparison	Rivaroxaban vs Apixaban	N/A	DOAC safety comparison	Similar safety between DOACs
Lee et al[17], 2019	Observational	84	Lung cancer with VTE	Lung cancer-specific	Rivaroxaban	Dalteparin	Efficacy and safety	Effective in lung cancer patients
Benzidia et al[19], 2022	Observational	95	Cancer patients with VTE	Multidisciplinary care	Various anticoagulants	Standard care	Care program effectiveness	Improved outcomes with coordinated care
Pelzer et al[28], 2014	Pilot	312	Pancreatic cancer	Pancreatic cancer-specific	Heparin with chemotherapy	Standard care	Safety and feasibility	Feasible in pancreatic cancer
How et al[18], 2024	Observational	486	Myeloproliferative neoplasms	Splanchnic vein thrombosis	Various anticoagulants	Variable	Management in MPN	Specialized considerations for MPN
Font et al[20], 2023	Observational	287	Cancer-associated VTE	Multinational study	Various anticoagulants	Variable	Adherence and QoL	International perspective on outcomes
Zabeida et al[31], 2023	Observational	146	Pediatric COVID-19	Children with coagulopathy	Anticoagulation	Variable	COVID-associated coagulopathy	Pediatric coagulation considerations

COVID-19: Coronavirus disease 2019; RCT: Randomized controlled trial; VTE: Venous thromboembolism; BID: Twice daily; GI: Gastrointestinal; GU: Genitourinary; LMWH: Low molecular weight heparin; DOAC: Direct oral anticoagulant; QoL: Quality of life; MPN: Myeloproliferative neoplasm; CAT: Cancer-associated thrombosis; N/A: Not applicable.