Rafael Gafoor1, Judith Charlton1, Rathi Ravindrarajah2, Martin C Gulliford3. 1. School of Population Health and Environmental Sciences, King's College London, London, United Kingdom. 2. School of Population Health and Environmental Sciences, King's College London, London, United Kingdom; University of Manchester, Centre for Primary Care, Division of Population Health, Health Services Research and Primary Care, London, United Kingdom. 3. School of Population Health and Environmental Sciences, King's College London, London, United Kingdom; NIHR Biomedical Research Centre at Guy's and St Thomas' Hospitals London, London, United Kingdom. Electronic address: martin.gulliford@kcl.ac.uk.
Abstract
OBJECTIVE: To evaluate association of first- or second-generation antipsychotic (AP) drugs with fracture risk at different levels of frailty over the age of 80 years. DESIGN: Population-based cohort study. SETTING AND PARTICIPANTS: United Kingdom Clinical Practice Research Datalink including 153,304 patients aged 80 years and older between 2006 and 2015. METHODS: Rates of fracture and adjusted rate ratios (RR) were estimated by AP drug exposure category, adjusting for age, sex, frailty, number of deficits, and dementia diagnosis. RESULTS: Data were analyzed for 165,726 treatment episodes (153,304 patients; 61.3% women; mean age 83 years; 21,365 fractures; 681,221.1 person-years of follow-up). AP exposure was associated with increasing age, frailty, and dementia diagnosis. After adjusting for frailty and covariates, first-generation AP exposure was associated with risk of any fracture, RR 1.24 (95% confidence interval 1.07-1.43, P = .003). Second-generation AP exposure was associated with femur fracture (RR 1.41, 1.22-1.64, P < .001) but less strongly with any fracture (RR 1.12, 1.01-1.24, P = .033). Fracture incidence increased with frailty level. The number of person-years of first-generation AP treatment associated with 1 additional fracture at any site was 75 (42-257) for severely frail patients but 187 (95% confidence interval 104-640) for 'fit' patients. For second-generation AP, 1 additional femur fracture might result from 173 (111-323) person-years treatment in severe frailty but 365 (234-681) person-years treatment for 'fit' patients. CONCLUSIONS AND IMPLICATIONS: Frail patients are more likely to receive AP drug treatment, but their absolute risk of AP-associated fracture is substantially greater than for nonfrail patients.
OBJECTIVE: To evaluate association of first- or second-generation antipsychotic (AP) drugs with fracture risk at different levels of frailty over the age of 80 years. DESIGN: Population-based cohort study. SETTING AND PARTICIPANTS: United Kingdom Clinical Practice Research Datalink including 153,304 patients aged 80 years and older between 2006 and 2015. METHODS: Rates of fracture and adjusted rate ratios (RR) were estimated by AP drug exposure category, adjusting for age, sex, frailty, number of deficits, and dementia diagnosis. RESULTS: Data were analyzed for 165,726 treatment episodes (153,304 patients; 61.3% women; mean age 83 years; 21,365 fractures; 681,221.1 person-years of follow-up). AP exposure was associated with increasing age, frailty, and dementia diagnosis. After adjusting for frailty and covariates, first-generation AP exposure was associated with risk of any fracture, RR 1.24 (95% confidence interval 1.07-1.43, P = .003). Second-generation AP exposure was associated with femur fracture (RR 1.41, 1.22-1.64, P < .001) but less strongly with any fracture (RR 1.12, 1.01-1.24, P = .033). Fracture incidence increased with frailty level. The number of person-years of first-generation AP treatment associated with 1 additional fracture at any site was 75 (42-257) for severely frail patients but 187 (95% confidence interval 104-640) for 'fit' patients. For second-generation AP, 1 additional femur fracture might result from 173 (111-323) person-years treatment in severe frailty but 365 (234-681) person-years treatment for 'fit' patients. CONCLUSIONS AND IMPLICATIONS: Frail patients are more likely to receive AP drug treatment, but their absolute risk of AP-associated fracture is substantially greater than for nonfrail patients.
Authors: Martin C Gulliford; Judith Charlton; Joanne R Winter; Xiaohui Sun; Emma Rezel-Potts; Catey Bunce; Robin Fox; Paul Little; Alastair D Hay; Michael V Moore; Mark Ashworth Journal: PLoS Med Date: 2020-07-23 Impact factor: 11.069