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Introduction: Current research on potentially inappropriate prescribing (PIP) in polymedicated older adults with atrial fibrillation (AF) and multimorbidity is predominantly focused on PIP of oral anticoagulants (OAC). Our study aimed to assess (i) the overall prevalence of PIP in older multimorbid adults with AF, (ii) potential associated factors of PIP, and (iii) the association of PIP with adverse health outcomes in a nationwide sample of Swedish older adults., Methods: Swedish national registries were linked to establish a cohort with a 2-year follow-up of older adults (≥65y) who, on 1 January 2017, had a diagnosis of AF and had at least one comorbidity (n = 203,042). PIP was assessed using the reduced STOPP/START version 2 screening tool. The STOPP criteria identify potentially inappropriate prescribed medications (PIM), while the START criteria identify potential prescribing omissions (PPO). PIP is identified as having at least one PIM and/or PPO. Cox regression analyses were conducted to examine the association between PIP and adverse health outcomes: mortality, hospitalisation, stroke, bleeding, and falls., Results: PIP was highly prevalent in older adults with AF, with both polypharmacy (69.6%) and excessive polypharmacy (85.9%). In the study population, benzodiazepines (22.9%), hypnotic Z-medications (17.8%) and analgesics (8.7%) were the most frequent PIM. Anticoagulants (34.3%), statins (11.1%), vitamin D and calcium (13.4%) were the most frequent PPO. Demographic factors and polypharmacy were associated with different PIM and PPO categories, with the nature of these associations differing based on the specific type of PIM and PPO. The co-occurrence of PIM and PPO, compared to appropriate prescribing, was associated with an increased risk of adverse health outcomes compared to all appropriately prescribed medications: cardiovascular (CV) (Hazard ratio (HR) [95% confidence interval] = 1.97 [1.88-2.07]) and overall mortality (HR = 2.09 [2.03-2.16]), CV (HR = 1.34 [1.30-1.37]) and overall hospitalisation (HR = 1.48 [1.46-1.51]), stroke (HR = 1.93 [1.78-2.10]), bleeding (HR = 1.10 [1.01-1.21]), and falls (HR = 1.63 [1.56-1.71])., Conclusion: The present study reports a high prevalence of PIP in multimorbid polymedicated older adults with AF. Additionally, a nuanced relationship between prescribing patterns, patient characteristics, and adverse health outcomes was observed. These findings emphasise the importance of implementing tailored interventions to optimise medication management in this patient population., Competing Interests: MG declares that he received a research grant from the Research Foundation Flanders (project number 11C0820N). Additionally, he declares payment to his institution for giving lectures to IPSA, a non-profit organisation. GL declares consultancy and speaker fees from BMS/Pfizer, Boehringer Ingelheim and Daiichi-Sankyo. MP declares that he is the President of the European Geriatric Medicine Society. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Amrouch, Vetrano, Damiano, Dai, Calderón-Larrañaga, Grymonprez, Proietti, Lip, Johnsen, Wastesson, Johnell, De Smedt and Petrovic.)

Background: Although non-vitamin K antagonist oral anticoagulants (NOACs) are recommended over vitamin K antagonists (VKAs) in atrial fibrillation (AF) management, direct long-term head-to-head comparisons are lacking. Therefore, their risk-benefit profiles were investigated compared to VKAs and between NOACs. Methods: AF patients initiating anticoagulation between 2013-2019 were identified in Belgian nationwide data. Inverse probability of treatment weighted Cox regression was used to investigate effectiveness and safety outcomes and were additionally stratified by NOAC dose. Results: Among 254,478 AF patients (328,796 person-years of follow-up), NOACs were associated with significantly lower risks of stroke or systemic embolism (stroke/SE) (hazard ratio (HR) 0.68, 95% confidence interval (CI) (0.64-0.72)), all-cause mortality (HR 0.76, 95%CI (0.74-0.79)), major or clinically relevant non-major bleeding (MB/CRNMB) (HR 0.94, 95%CI (0.91-0.98)) and intracranial hemorrhage (HR 0.73, 95%CI (0.66-0.79)), but non-significantly different risks of myocardial infarction, gastrointestinal and urogenital bleeding compared to VKAs. Despite similar stroke/SE risks, dabigatran and apixaban were associated with significantly lower MB/CRNMB risks compared to rivaroxaban (HR 0.86, 95%CI (0.83-0.90); HR 0.86, 95%CI (0.83-0.89), respectively) and edoxaban (HR 0.91, 95%CI (0.83-0.99); HR 0.86, 95%CI (0.81-0.91), respectively), and apixaban with significantly lower major bleeding risks compared to dabigatran (HR 0.86, 95%CI (0.80-0.92)) and edoxaban (HR 0.79, 95%CI (0.72-0.86)). However, higher mortality risks were observed in some risk groups including with apixaban in patients with diabetes or concomitantly using digoxin compared to dabigatran and edoxaban, respectively. Conclusion: NOACs had better long-term risk-benefit profiles than VKAs. While effectiveness was comparable, apixaban was overall associated with a more favorable safety profile followed by dabigatran., Competing Interests: Outside this manuscript, TDB has served as a chairperson during a lecture for Bayer and Daiichi Sankyo, and participated in an expert meeting for Pfizer. Outside this manuscript, SS has given a lecture sponsored by BMS. Neither author has received any fees personally. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Grymonprez, De Backer, Bertels, Steurbaut and Lahousse.)

Background and Objective: Atrial fibrillation (AF), the most common cardiac arrhythmia, typically increases with age. Oral anticoagulants (OACs) are the cornerstone of treatment to reduce the associated risk for systemic thromboembolism. Four large randomized controlled trials (RCTs) have shown that non-vitamin K antagonist oral anticoagulants (NOACs) are non-inferior to vitamin K antagonists (VKAs) in preventing stroke and systemic embolism, as well as regarding their risk for major bleeding. However, as vulnerable geriatric patients with AF were largely underrepresented in these trials, physicians are faced with the challenge of choosing the right anticoagulant for geriatric patients in real-life clinical practice. In this vulnerable patient group, NOACs tend to be underused or underdosed due to concerns of excessive fall-related intracranial bleeding, cognitive impairment, multiple drug-drug interactions, low body weight or impaired renal function. As life expectancy continues to rise worldwide, the number of geriatric patients substantially increases. Therefore, there is an urgent need for a critical appraisal of the added value of NOACs in geriatric patients with AF at high thromboembolic and bleeding risk., Methods and Results: This systematic review provides an overview of the literature on the impact of increased age (≥75 years), multimorbidity, polypharmacy, increased falling risk, frailty and dementia on the effectiveness and safety of NOACs as compared to VKAs, after searching the Medline database. Moreover, a meta-analysis on the impact of increased age ≥75 years old was performed after pooling results from 6 post hoc analyses of RCTs and 6 longitudinal observational cohort studies, highlighting the superior effectiveness (hazard ratio (HR) 0.83, 95% confidence interval (CI) [0.74-0.94] for stroke/SE; HR 0.77, 95%CI [0.65-0.92] for mortality) and non-inferior safety (HR 0.93, 95%CI [0.86-1.01] for major bleeding; HR 0.58, 95%CI [0.50-0.67] for intracranial bleeding; HR 1.17, 95%CI [0.99-1.38] for gastrointestinal bleeding) of NOACs versus VKAs in older AF patients., Conclusion: Across geriatric subgroups, apixaban was consistently associated with the most favourable benefit-risk profile and should therefore be preferred in geriatric patients with AF. However, research gaps on the impact of increased falling risk, frailty and baseline dementia were identified, requiring careful consideration while awaiting more results., (Copyright © 2020 Grymonprez, Steurbaut, De Backer, Petrovic and Lahousse.)