Table 4 Current international treatment guideline recommendations for the treatment of cancer-associated VTE

ISTH 2018^a (69)

• Patients with low bleeding risk and no drug–drug interactions: edoxaban or rivaroxaban; LMWHs are acceptable alternatives.

• Patients with high bleeding risk^c: LMWH; edoxaban or rivaroxaban as an alternative if no potential DDI.

• No specific recommendation.

ESC 2019^a (70)

• PE and cancer: LMWH for the first 3–6months (classIIa, levelA).

• Edoxaban (classIIa, level B) or rivaroxaban (classIIa, levelC) may be used except in GI cancer patients.

• Extend indefinitely or until the cancer is cured (classIIa, levelB).

• Consider LMWH, NOAC or VKA.

ASCO 2019^a (71)

• LMWH, UFH, fondaparinux or rivaroxaban.

• Offer LMWH, NOACs or VKAs beyond the initial 6months to select patients with active cancer, such as those with metastatic disease or those receiving chemotherapy.

o LMWH, edoxaban or rivaroxaban preferred.

o LMWH preferred in settings with increased bleeding risk.

• Assess intermittently to ensure a continued favorable risk-benefit profile

ITAC 2019^a (72)

• LMWH when CrCl ≥ 30mL/min (grade1B).

• Rivaroxaban (first 10days) or edoxaban (started after initial LMWH/UFH for 5 days) can be used for initial treatment if CrCl ≥ 30mL/min and patient is not at high risk of GI or GU bleeding (grade1B).

• LMWH or DOACs for ≥ 6 months (grade1A)

– DOACs when CrCl ≥ 30mL/min if no impairment in GI absorption or strong DDIs (grade1A), but caution advised in GI malignancies, especially upper GI tract.

• After 6months, termination or continuation of anticoagulation based on benefit-risk ratio, tolerability, drug availability, patient preference and cancer activity (guidance).

NICE 2020^a (73)

• Consider DOAC if active cancer and confirmed proximal DVT or PE.

• If DOAC unsuitable, consider LMWH alone or VKA (following initial LMWH).

• Choice of anticoagulant should consider tumor site, drug-drug interactions and bleeding risk.

• Review treatment at 3–6months according to clinical need.

ACCP 2021^b (76)

• Apixaban, edoxaban or rivaroxaban (strong recommendation).

─ Apixaban or LMWH may be preferred in luminal GI malignancies.

• Extended-phase (> 3months) DOAC therapy (apixaban, edoxaban or rivaroxaban) (strong recommendation)

Reassess periodically.

ASH 2021^b (74)

• DOAC (apixaban or rivaroxaban) or LMWH (conditional recommendation).

– Caution with DOACs in GI cancers.

• Treat for 3–6 months with a DOAC (apixaban, edoxaban or rivaroxaban) over LMWH or VKA (conditional recommendations).

• Treat for > 6 months rather than short-term (3–6months) in patients with active cancer (conditional recommendation).

Suggest continuing indefinitely rather than stopping after completion of a definitive period of anticoagulation (conditional recommendation).

Use a DOAC or LMWH (conditional recommendation).

NCCN 2022^b (75)

• Apixaban (category 1), edoxaban after ≥ 5days of parenteral anticoagulation (category 1) or rivaroxaban (category2A) preferred for patients without gastric or gastroesophageal lesions.

Apixaban may be safer than edoxaban or rivaroxaban for patients with gastric or gastroesophageal lesions (category 2B)

Caution in GU tract lesions.

• LMWH (dalteparin) preferred for patients with gastric or gastroesophageal lesions (category1).

• Dabigatran if above regimens not appropriate or unavailable.

• ≥ 3months or as long as active cancer or cancer therapy.