The safety, effectiveness, and cost-effectiveness of anticoagulants among individuals with cancer-associated venous thromboembolism

Abstract

Cancer-associated venous thromboembolism (CAT) stands as the second leading cause of mortality among individuals with cancer, accompanied by heightened risks of recurrent venous thromboembolism (VTE) and bleeding. The conventional approach involves administering subcutaneous injections of low-molecular-weight heparin (LMWH) for at least 3-6 months, which can lead to lower adherence. Direct oral anticoagulants (DOACs), present an oral alternative that enhances individuals' compliance because of its ease of administration. However, a crucial clinical question remains: Is switching to DOACs after LMWH therapy both safe and effective for individuals with CAT? Moreover, the comparative cost-effectiveness of DOACs versus LMWH in CAT management within the Hong Kong healthcare system is unknown. Additionally, during the pandemic, the lower vaccination rate among individuals with cancer may be primarily attributed to concerns regarding the safety of Coronavirus disease 2019 (COVID-19) vaccines, including the risk of thromboembolism. This thesis aimed to address these knowledge gaps through three primary objectives: 1) To assess the risks of recurrent VTE, major bleeding, and all-cause mortality of switching to DOACs versus continuous use of LMWH in individuals with CAT; 2) To evaluate the cost-effectiveness of DOACs compared to LMWH in individuals with CAT; 3) To understand the safety profiles of the BNT162b2 and CoronaVac vaccines in individuals with cancer. Utilizing the territory-wide electronic databases from Hong Kong and Taiwan, two retrospective cohort studies were conducted to assess the safety and effectiveness of medications, along with cost-effective analyses to compare their healthcare expenditures. The key findings revealed that compared to continuous use of LMWH, switching to DOACs was associated with reduced risks of all-cause mortality, with no increase in recurrent VTE or major bleeding among both Hong Kong and Taiwanese populations with CAT. Moreover, DOACs demonstrated greater Quality-Adjusted Life Year (QALY) enhancements and lower overall costs, establishing themselves as a cost-effective alternative to LMWH for CAT management in Hong Kong. Furthermore, no escalated risk of adverse events of special interest, including thromboembolism, was observed following the administration of two doses of either BNT162b2 or CoronaVac vaccines among individuals with cancer in Hong Kong. This research delved into the safety, effectiveness, and cost-effectiveness of switching to DOACs from LMWH therapy in individuals with CAT, particularly focusing on Asian populations who may be at a higher risk of bleeding. Moreover, it assuages concerns regarding the safety of COVID-19 vaccines among individuals with cancer. The conclusions indicate that compared to continuous LMWH therapy, switching to DOACs offers superior or equivalent safety, effectiveness, and cost-effectiveness, making them a recommended choice for short-term and long-term anticoagulation in individuals with CAT. Moreover, the findings advocate for the utilisation of DOACs specifically in the older people, end-stage cancer, gastrointestinal malignancy, platinum-therapy regimen, poorer health status, and those with higher VTE and/or bleeding risk, regardless of their initial duration of LMWH therapy. Our research offers valuable real-world evidence to extend individual survival, guide clinical medication decisions, and optimize the allocation of healthcare resources to achieve greater impact.