Oral anticoagulants in Australia: large-scale evidence on use, costs and transitions in treatment following the introduction of novel therapies

Abstract

Cardiovascular disease is a major public health concern: it is the leading cause of mortality worldwide. Effective treatment and prevention are critical to improving outcomes. Oral anticoagulants reduce the formation and development of blood clots, a common underlying pathology of some cardiovascular diseases. Their uses include prevention of ischaemic stroke in people with atrial fibrillation, and prevention and treatment of venous thromboembolism, including following major orthopaedic surgery. Shortfalls in oral anticoagulant use contribute to avoidable morbidity and mortality from stroke and venous thromboembolism. Direct oral anticoagulants (DOACs)-introduced globally in the late 2000s-had the potential to improve treatment by avoiding certain limitations of existing therapy with warfarin. Despite their importance, evidence on the use of DOACs and their role in enhancing cardiovascular disease prevention in Australia is limited. The ultimate aim of this thesis is to improve cardiovascular disease prevention by providing evidence on oral anticoagulant use in Australia. Four pharmacoepidemiological studies quantifying: (i) changes in population dispensing of oral anticoagulants; (ii) oral anticoagulant use following hospitalisation with atrial fibrillation, venous thromboembolism or major orthopaedic surgery; (iii) the relationship of health and sociodemographic factors to oral anticoagulant use and (iv) post-discharge continuation of oral anticoagulants and health service use; combined with reviews of published evidence, were undertaken to address this aim. Evidence from a 10% sample of Pharmaceutical Benefits Scheme (PBS) data from 2005-16 showed that within three years of their expanded indication into stroke prevention in atrial fibrillation in 2013, DOAC use grew such that the annual number of people dispensed any oral anticoagulant increased by 44%, the proportion of people dispensed warfarin decreased from 99% to 36% and government expenditure on oral anticoagulants increased 8-fold. Analysis of data from the 45 and Up Study, Australia's largest ongoing study into health and ageing, linked to PBS, Medicare Benefits Schedule, hospitalisation and death records from 2006-17 showed the proportion dispensed oral anticoagulants on discharge increased from: 24.4% in 2006-09 to 42.5% in 2014-17 following hospitalisation with atrial fibrillation; 65.5% to 70.7% with pulmonary embolism; 44.0% to 44.8% with deep vein thrombosis; and 2.8% to 10.0% with hip, and 4.8% to 8.3% with knee replacement surgery. Further analyses of the same dataset found that only 17.7% of those hospitalised with atrial fibrillation used an oral anticoagulant for at least twelve months. Among those with atrial fibrillation, oral anticoagulant use was more common in females, people aged 65-74 years, those who were obese and those with risk factors for stroke compared to other cohort members; use was two and a half times higher among those with the most compared to no stroke risk factors. Use of oral anticoagulants was less common among those reporting current smoking and among those with comorbidities including kidney disease, liver disease and cancer; use was lowest with the most comorbidities. Oral anticoagulant users experienced more readmissions for atrial fibrillation and ischaemic stroke or systemic embolism within three months post-discharge, likely reflecting increased use in people with more risk factors. This thesis found that, in Australia, access to government-subsidised DOACs both replaced warfarin and increased overall use and costs of oral anticoagulation, especially for stroke prevention in atrial fibrillation. Importantly, large shortfalls in use remain, with around 45% of people hospitalised with atrial fibrillation dispensed oral anticoagulants post-discharge, and only 17.7% using therapy for one year or longer. Identifying and addressing barriers and enablers to optimal oral anticoagulant use remains an important prevention priority.