| アブストラクト | BACKGROUND: In older patients (>/=65 years), the evidence for continued statin prescription is scarce. Although statins are commonly discontinued in the context of advancing age or frailty, there is little evidence to guide decision making. Hence, we aimed to investigate the risks and benefits of statin discontinuation in older people, stratified by frailty status. METHODS: In this English population-wide retrospective cohort study, we used Clinical Practice Research Datalink (CPRD) GOLD data of routinely collected and anonymised patient records. Eligible patients were registered at a general practice providing research-quality data between Jan 1, 1998, and May 20, 2021. The inclusion criteria were persistent statin users (defined as a statin medication possession ratio of 80% or more for any statin during the preceding 12 months before study entry) aged 65 years or older and Hospital Episode Statistics (HES) and Office for National Statistics linkage availability. Eligible patients were persistent statin users registered with an up-to-standard practice contributing to CPRD GOLD. Statin discontinuation was defined as no new prescription in the 180 days after the last prescription expired. Participants who discontinued statins were matched within the practice to two randomly selected statin continuers, who were actively taking statins on the discontinuation date. The primary outcome measure was all-cause hospitalisation, defined as a new admission date in HES with discharge data after at least 24 h of admission, measured at 1 year and 5 years of the index date. The effect of statin discontinuation was examined using Fine-Gray models accounting for the competing risk of death. Results were stratified by electronic frailty index category (fit, mild frailty, moderate frailty, and severe frailty), dementia, care home residency, or housebound status in the preceding year. RESULTS: We identified 383 342 eligible persistent stain users, of whom 65 727 participants discontinued statins and were matched with 131 453 participants who continued statins (mean age 75.9 years [SD 7.2], 98 378 [49.9%] female and 65 727 [50.1%] male) over a mean follow-up period of 4.1 years (SD 3.3). After Inverse probability of treatment weighting, there were 136 100 participants who continued a statin and 61 080 who discontinued. There were 94 725 hospital admissions over 551 178 person-years, with crude incidence rates of 199.7 per 1000 person-years (95% CI 197.5-201.9) in those who discontinued statin therapy and 160.2 per 1000 person-years (158.9-161.5) in those who continued statin therapy. Discontinuation was associated with an increased relative risk of all-cause hospitalisation at 1 year in the whole cohort (subdistribution hazard ratio [sHR] 1.22 [95% CI 1.20-1.25]; absolute risk difference [ARD] per 1000 patients 37.6 [95% CI 33.7-41.4]). The relative risk reduced with increasing frailty (fit sHR 1.30 [95% CI 1.24-1.37], ARD per 1000 patients 30.2 [95% CI 24.7-35.8]; mild frailty sHR 1.22 [1.18-1.26], ARD per 1000 patients 38.5 [32.1-45.6]; and moderate frailty sHR 1.16 [1.10-1.21], ARD per 1000 patients 40.0 [28.2-53.4]), and there was no association between statin discontinuation and an increased risk of all-cause hospitalisation among patients with severe frailty (sHR 1.03 [0.94-1.12], ARD per 1000 patients 9.0 [-19.9 to 34.8]) or dementia (sHR 1.05 [0.99-1.12], ARD per 1000 patients 13.6 [-0.4 to 33.4]), and among care home residents (sHR 0.76 [0.63-0.90], ARD per 1000 patients -68.8 [-112.8 to -27.0]); a small increased risk was observed among those who were housebound (sHR 1.07 [1.02-1.12], ARD per 1000 patients 20.8 [5.5-35.1]). At 5 years, statin discontinuation was associated with an increased relative risk of all-cause hospitalisation in the whole cohort (sHR 1.11 [95% CI 1.09-1.12]; ARD per 1000 patients 36.9 [31.5-41.5]). Again, this risk reduced with increasing frailty (fit sHR 1.14 [95% CI 1.11-1.17], ARD per 1000 patients 41.1 [95% CI 32.3-50.4]; mild frailty sHR 1.11 [1.08-1.13], ARD per 1000 patients 37.4 [29.4-45.9]; and moderate frailty sHR 1.04 [1.01-1.08], ARD per 1000 patients 15.2 [5.9-27.7]), and there was no association between statin discontinuation and an increased risk of all-cause hospitalisation among participants with severe frailty (sHR 0.94 [0.88-1.00], ARD per 1000 patients -19.7 [-40.9 to -2.0]) or dementia (sHR 0.95 [0.91-0.99], ARD per 1000 patients -20.2 [-38.5 to -0.3]), among care home residents (sHR 0.71 [0.62-0.81], ARD per 1000 patients -120.4 [-173.0 to -70.3]), and in those who were housebound (sHR 0.96 [0.93-1.00], ARD per 1000 patients -12.5 [-25.6 to 1.1]). INTERPRETATION: In older adults, statin discontinuation was associated with an increased risk of hospitalisation, although this association diminished with increasing frailty. These findings could inform individualised deprescribing decisions, although residual confounding can hinder causal interpretation. FUNDING: National Institute of Health Research and Wellcome Trust. |
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| 投稿者 | Seeley, Anna E; van der Veen, Rik; Wang, Ariel; Glogowska, Margaret; Hayward, Gail; Williamson, Esther; Sheppard, James P |
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| 組織名 | Nuffield Department of Primary Care Health Sciences, University of Oxford,;Oxford, UK. Electronic address: anna.seeley@phc.ox.ac.uk.;Oxford, UK.;Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences,;University of Oxford, Oxford, UK; Faculty of Health and Life Sciences, University;of Exeter, Exeter, UK. |
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