Authors' objectives: To assess the effectiveness, safety and cost-effectiveness of prophylactic anticoagulation in ambulatory cancer patients.

Authors' results and conclusions: Effectiveness: There was good level of evidence to suggest that prophylactic anticoagulation with low-molecular-weight heparins (LWMH) or direct oral anticoagulants (DOAC) were associated with significant reduction in venous thromboembolism (VTE) events when given to ambulatory cancer patients compared with placebo or no thromboprophylaxis. Similar benefit was observed in specific populations such as lung and pancreatic cancer patients receiving LMWH thromboprophylaxis. Two studies showed greater risk reduction among ambulatory cancer patients with high risk for VTE (Khorana score ≥3), suggesting that a Khorana score risk-stratified strategy may be considered. However, prophylactic anticoagulation with LMWH or DOAC appeared to have no effect on mortality in ambulatory cancer patients compared with placebo or no thromboprophylaxis. Safety: There was good level of evidence to suggest that prophylactic anticoagulation with LMWH was not associated with significant increase in risk of major bleeding, thrombocytopaenia and adverse events; and prophylactic anticoagulation with DOAC was not associated with significant increase in risk of major bleeding and clinically relevant non-major bleeding (CRNMB). There was no significant increase in risk of major bleeding in lung and pancreatic cancer patients receiving LMWH thromboprophylaxis and high-risk patients receiving DOAC thromboprophylaxis. However, the risk of bleeding, while not reaching statistical significance, suggests caution when prophylactic anticoagulation is considered for ambulatory cancer patients. Cost-effectiveness: One study showed that DOAC thromboprophylaxis for six months appeared to be cost-effective in ambulatory cancer patients who were at intermediate-to-high risk for VTE with an incremental cost of US$1,445, QALY increase of 0.12, and an international cost-effectiveness ratio (ICER) of US$11,947 per QALY gained. When given to high-risk patients only, DOAC thromboprophylaxis appeared to be more cost-effective with an incremental cost of US$1,103, QALY increase of 0.19 and an ICER of US$5,794 per QALY gained. Another study showed that LMWH thromboprophylaxis appeared to be economically reasonable with an incremental cost of US$3,213, QALY increase of 0.0354 QALYs and an ICER of US$90,893 per QALY gained; and would remain economically reasonable if future trials confirm its suggested mortality benefit. However, in this review, LMWH prophylaxis appeared to have no mortality benefit for ambulatory cancer patients. The model also did not include downstream VTE morbidities, of which inclusion of related costs would likely have made LMWH more cost-effective. Organisational issues: The Khorana score may help clinicians in selecting patients at high risk of VTE. However, a substantial number of cancer patients with VTE may not be identified via the Khorana score and may, therefore, not benefit from thromboprophylaxis. More evidence is needed to ascertain the performance of Khorana score in selecting ambulatory cancer patients at high risk for VTE.

Authors' recommendations: Based on the review, prophylactic anticoagulation with LMWH or DOAC may be given to selected ambulatory cancer patients who are considered to be at high risk of VTE and low risk of bleeding.

Authors' methods: Electronic databases were searched through the PubMed and Ovid interface: MEDLINE (1946 to present), EBM Reviews–Cochrane Database of Systematic Reviews (2005 to 4th March 2020), EBM Reviews–Cochrane Central Register of Controlled Trials (January 2020), EBM Reviews–Database of Abstracts of Review of Effects (1st Quarter 2016), EBM Reviews–Health Technology Assessment (4th Quarter 2016), NHS economic evaluation database (1st Quarter 2016). Searches were also run in INAHTA, horizon scanning databases, FDA website and general search engine. Additional articles were identified from reviewing the references of retrieved articles. The last search was run on 5th March 2020.

Project Status: Completed

URL for project: https://www.moh.gov.my/index.php/database_stores/store_view/30?mid=609

Year Published: 2020

URL for published report: https://www.moh.gov.my/index.php/database_stores/store_view_page/30/352

Requestor: Ministry of Health

English language abstract: An English language summary is available

Publication Type: Mini HTA

Country: Malaysia

Organisation Name: Malaysian Health Technology Assessment

Contact Address: Malaysian Health Technology Assessment Section, Ministry of Health Malaysia, Federal Government Administrative Centre, Level 4, Block E1, Parcel E, 62590 Putrajaya Malaysia Tel: +603 8883 1229

Contact Name: htamalaysia@moh.gov.my

Contact Email: htamalaysia@moh.gov.my

Copyright: Malaysian Health Technology Assessment Section (MaHTAS)