Background Direct oral anticoagulants are available for patients with atrial fibrillation. Objective This study compared adherence and persistence of once-daily (QD) vs twice-daily (BID) direct oral anticoagulants in patients with atrial fibrillation. Methods A cohort study was conducted in three databases in the Netherlands, Italy and Germany. Patients with AF starting direct oral anticoagulants after drug approval date were included. The index date was the date of first dispensing. Study patients were restricted to those aged ≥ 18 years, ≥ 1 year database history and ≥ 1 year follow-up. Adherence to treatment was defined as the proportion of days covered ≥ 80% between the index date and the date of last dispensing of the index regimen (i.e. exposure period). The proportion of days covered was also determined during the 12-month follow-up. Persistence was defined as continuous use from index to treatment discontinuation. Results In the Netherlands, Italy and Germany, respectively, 6068, 32,260 and 167,445 patients were included. The mean age of the patients was 70, 77 and 74 years, and 31%, 40% and 61% were QD users, all respectively. Among QD/BID users, 93/90%, 88/86% and 77/58%, respectively were adherent during the exposure period. Persistence rates at 1 year in QD/BID users were 60/59%, 13/14% and 46/31%, respectively. Conclusions Adherence to treatment was high. In Germany, adherence was markedly higher in QD users compared with BID users. In Italy and the Netherlands, these differences were marginal. Persistence was low in all countries, but discontinuation was temporary. Only in Germany, persistence was markedly lower in BID users vs QD users.Elisabeth Smits and Felicita Andreotti share first authorship.

Background A high degree of adherence to direct oral anticoagulants is essential for reducing the risk of ischaemic stroke and systemic embolism in patients with atrial fibrillation, owing to the rapid decline in anticoagulation activity when doses are omitted (i.e. rebound effect). Objective We aimed to assess the relationship between non-adherence and non-persistence with direct oral anticoagulants and the incidence of ischaemic stroke in patients with atrial fibrillation. Methods A nested case–control study was conducted in the Netherlands, Italy and Germany among patients with atrial fibrillation starting direct oral anticoagulants between the drug approval date and the end of database availability. Patients with an ischaemic stroke during the follow-up were selected as cases and compared with matched controls (matched on age ± 5 years, sex, year of cohort entry date and CHA 2 DS 2 -VASc-score at cohort entry date). The cohort entry date was the first dispensing date. Study patients were those aged ≥ 45 years, with ≥ 1 year database history, ≥ 1 year follow-up and at least two direct oral anticoagulant dispensings after the cohort entry date. Adherence and persistence to direct oral anticoagulant treatment were defined as the proportion of days covered ≥ 80% or direct oral anticoagulant continuous use between the cohort entry date and the index date (i.e. date of ischaemic stroke), respectively. Results In The Netherlands, Italy and Germany, 105 cases and 395 controls, 1580 cases and 6248 controls, and 900 cases and 3570 controls were included, respectively. Odds ratios (ORs) for stroke among current users who were non-adherent compared to adherent users were 0.43 (95% confidence interval [CI] 0.09–1.96) in The Netherlands, 1.11 (95% CI 0.98–1.26) in Italy and 1.21 (95% CI 1.01–1.45) in Germany. The risk of stroke was significantly higher among non-persistent users compared with persistent users in all three databases [OR 1.56 (95% CI 1.00–2.44), OR 1.48 (1.32–1.65) and OR 1.91 (95% CI 1.64–2.22), respectively]. In The Netherlands and Germany, the risk of stroke was higher the longer a patient had stopped using direct oral anticoagulants. Conclusions Both non-adherence (in Germany) and non-persistence increased the risk of stroke, either using a once-daily or twice-daily regime. Supplementary Information The online version contains supplementary material available at 10.1007/s40801-022-00317-3.

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Alzheimer's dementia, Alzheimer's dementia, and cognitive impairment. Logistic regressions were used to examine the potential risk factors of earlyonset dementia among PLWHA. Explanatory variables included were gender, race, year of birth, education level, and income level. Results: A total of 44,940 PLWHA aged 20-64 were included in Optum during the period 2007-2016. A younger age was associated with a smaller risk of developing early-onset dementia (non-Alzheimer's dementia OR: 0.92; Alzheimer's dementia OR: 0.93; cognitive impairment OR: 0.94; all statistically significant at p-value,0.05). Being African-American was associated with smaller risk of developing early-onset cognitive impairment (OR: 0.82; p=0.07; statistically significant at p-value,0.1). Odds ratios for male, education level, and income level were all not statistically significant. Conclusions: Aging is a potential risk factor of developing early-onset dementia even in PLWHA under age 64 in this private insurance dataset. Although the odds ratios for male, race, education level, and income level, may not be statistically significant in all 3 examined dementia-related conditions, we cannot preclude their involvement in early-onset dementia among PLWHA. Further investigation is needed to explore potential risk factors of early-onset dementia among PLWHA.