Evolving Trends in Consumption of Direct Oral Anticoagulants in 65 Countries/Regions from 2008 to 2019.

BACKGROUND: Direct oral anticoagulants (DOACs) have been increasingly utilised over warfarin. However, little is known about the relative consumption trends and costs of each DOAC at the global level. METHODS: An ecological study using pharmaceutical sales data from IQVIA-MIDAS database was used to estimate consumption and cost of individual DOACs in 65 countries from 2008 to 2019. Consumption was estimated from the volume of DOACs sold, expressed as defined-daily-dose/1000-inhabitants/day (DDDTID). Compound and absolute annual growth rates were reported to quantify consumption changes over time. Costs were estimated as manufacturer price per day-of-therapy. RESULTS: Global consumption of dabigatran, rivaroxaban, apixaban and edoxaban were 0.31, 1.05, 1.08 and 0.78 DDDTID, respectively, in Q2-2019, compared to 0.23, 0.54, 0.21 and 0.03 in Q2-2015, with highest consumption in Western Europe, Northern Europe and Oceania (18.2, 14.07, 13.14 DDDTID). In most countries (46/65, 70%), rivaroxaban contributed to most DOAC consumption (35%-100%), whereas dabigatran accounted for less than one-third. Edoxaban accounted for < 20% of the total in Northern America and Europe but contributed significant proportions in Japan (28.58%) and South Korea (31.37%). Longer median time-to-adoption from FDA approval for apixaban and edoxaban was observed. Costs of all DOACs were ~2-4 times higher in the USA, Puerto Rico and Thailand than in other countries. CONCLUSIONS: Regional differences exist in consumption pattern and trends of individual DOACs over the past decade. Consumption of rivaroxaban and apixaban overtook dabigatran in most countries, whereas use of edoxaban remains limited except in East Asian countries. The USA pays higher prices for DOACs than other countries.

Cost-Effectiveness of Midazolam Versus Haloperidol Versus Olanzapine for the Management of Acute Agitation in the Accident and Emergency Department.

OBJECTIVES: A multicenter randomized clinical trial in Hong Kong Accident and Emergency (A&E) departments concluded that intramuscular (IM) olanzapine is noninferior to haloperidol and midazolam, in terms of efficacy and safety, for the management of acutely agitated patients in A&E setting. Determining their comparative cost-effectiveness will further provide an economic perspective to inform the choice of sedative in this setting. METHODS: This analysis used data from a randomized clinical trial conducted in Hong Kong A&E departments between December 2014 and September 2019. A within-trial cost-effectiveness analysis comparing the 3 sedatives was conducted, from the A&E perspective and a within-trial time horizon, using a decision-analytic model. Sensitivity analyses were also undertaken. RESULTS: In the base-case analysis, median total management costs associated with IM midazolam, haloperidol, and olanzapine were Hong Kong dollar (HKD) 1958.9 (US dollar [USD] 251.1), HKD 2504.5 (USD 321.1), and HKD 2467.6 (USD 316.4), respectively. Agitation management labor cost was the main cost driver, whereas drug costs contributed the least. Midazolam dominated over haloperidol and olanzapine. Probabilistic sensitivity analyses supported that midazolam remains dominant > 95% of the time and revealed no clear difference in the cost-effectiveness of IM olanzapine versus haloperidol (incremental cost-effectiveness ratio 667.16; 95% confidence interval -770.89, 685.90). CONCLUSIONS: IM midazolam is the dominant cost-effective treatment for the management of acute agitation in the A&E setting. IM olanzapine could be considered as an alternative to IM haloperidol given that there is no clear difference in cost-effectiveness, and their adverse effect profile should be considered when choosing between them.

Health-related quality of life (HRQL) and continuous antipsychotic treatment: 3-year results from the Schizophrenia Health Outcomes (SOHO) study.

OBJECTIVES: We investigated the association between continuous antipsychotic use and health-related quality of life (HRQL) 3-year change in the European Schizophrenia Outpatients Health Outcomes (EU-SOHO) study. METHODS: EU-SOHO is an observational study of outcomes associated with antipsychotic treatment for schizophrenia in an outpatient setting. HRQL was assessed at study entry and at 6, 12, 18, 24, 30, and 36 months using the EuroQol-5D (EQ-5D). UK population time trade-off (TTO) tariffs were applied to the self-rated EQ-5D health states to calculate HRQL ratings (0 = death, 1 = best). An epoch analysis approach was used as a conceptual framework to analyze the longitudinal data. Follow-up was divided into epochs or periods of continuous treatment. When a patient changed antipsychotic treatment, he or she was considered to have a new observation. Multilevel models were employed to evaluate the association of HRQL with medication and other clinical and sociodemographic variables for each epoch. A total of 9340 patients were analyzed (42.1% women; mean age 40 years). RESULTS: Mean EQ-5D scores increased over time; the largest improvement occurred in the first 6 months (mean increase of 0.19). Longer duration of illness and older age at first treatment were associated with worse baseline EQ-5D scores. Improvements in EQ-5D scores were greater for more socially active patients or those in paid employment. Few significant differences were found between antipsychotic medications. Olanzapine and clozapine were associated with higher HRQL increases. CONCLUSIONS: Continuous antipsychotic treatment is associated with important HRQL benefits at 3 years, most of which occurs during the first 6 months. Although some medications are associated with better HRQL outcomes, differences are small.