Thiazide diuretics and the risk of hip fracture after stroke: a population-based propensity-matched cohort study using Taiwan’s National Health Insurance Research Database

Abstract

ObjectivesThis study aimed to investigate the association between thiazide use and the risk of hip fracture after stroke.SettingA population-based, propensity-matched cohort study was conducted on the basis of Taiwan’s National Health Insurance Research Database.ParticipantsPatients with newly diagnosed ischaemic stroke between 2000 and 2011 were included. After propensity score matching, 7470 patients were included, of whom 3735 received thiazides and 3735 did not.Outcome measuresHRs for developing hip fractures within 2 years after stroke were calculated using Cox proportional hazards regression model with adjustments for sociodemographic and coexisting medical conditions.ResultsOverall, patients using thiazides after stroke had a lower risk of hip fracture than those not using thiazides (8.5 vs 13.9 per 1000 person-years, adjusted HR=0.64, 95% CI 0.46 to 0.89, p=0.007). Further sensitivity analysis based on the duration of thiazide use revealed that the risk of hip fracture tended to decrease as the duration of exposure of thiazides increased. However, the effect was significant only in patients with long-term use of thiazides (using thiazides for >365 days within 2 years after stroke), with a 59% reduction in the risk of hip fracture when compared with patients not using thiazide (adjusted HR=0.41, 95% CI 0.22 to 0.79, p=0.008).ConclusionsThe long-term use of thiazides is associated with a decreased risk of hip fracture after stroke.

Association between diuretic use and the risk of vertebral fracture after stroke: a population-based retrospective cohort study

“…Nevertheless, our study has several limitations that should be mentioned. First, we could not retrieve some clinical data, including patient lifestyles and physical, psychiatric, or laboratory examination data (e.g., BMD, body mass index, smoking status, and alcohol use) from the NHI research database [43], and they might represent confounding factors of fracture risk. Even if we had an adequate study design, including propensity score matching to balance baseline differences between groups and further use of a multivariate Cox proportional hazards regression model to eliminate residual confounding effects, bias related to unknown or unmeasured confounders might still exist.…”

“…We also could not identify the exact mechanism of how the vertebral fracture occurred to distinguish whether the fracture was caused by osteoporosis or a trauma event. Third, because of the patient anonymity policy in the NHI research database, we could not confirm the accuracy of the patients’ diagnoses by contacting the patients directly [43]. We also could not obtain the detailed image reports in the claims-based dataset; thus, we could not determine what types of image and how such image examination confirmed the vertebral fracture.…”

“…As our previous study evaluated the association between thiazides and hip fracture [43], we retrieved all prescription data for thiazides and loop diuretics within 2 years after the diagnosis of new-onset stroke to evaluate the association between diuretic use and the risk of vertebral fractures. Patients who were prescribed thiazides within 2 years after stroke were defined as the thiazide cohort, those who were prescribed loop diuretics comprised the loop diuretic cohort, and those who had not been prescribed any thiazides or loop diuretics were defined as the comparison cohort.…”

“…Patients who were prescribed thiazides within 2 years after stroke were defined as the thiazide cohort, those who were prescribed loop diuretics comprised the loop diuretic cohort, and those who had not been prescribed any thiazides or loop diuretics were defined as the comparison cohort. To further evaluate the effects of short- and long-term exposure to diuretics, both the thiazide and loop diuretic cohorts were divided into three subgroups [43]: patients with exposure duration of 1–90, 91–365, and > 365 days within 2 years following stroke.…”

“…Urbanization in Taiwan was categorized into seven levels [47, 48], with a lower level indicating a higher degree of urbanization. Levels 5 through 7 were combined into a single group to simplify the analysis [43].…”