Association between alpha blocker use and the risk of fractures in patients with chronic kidney disease: a cohort study

BACKGROUND: Alpha blockers (ABs) are frequently prescribed to patients with chronic kidney disease (CKD), which is often complicated by refractory hypertension (HT). Although there have been several reports on the association between AB use and the risk of fractures, their conclusions have not yet been drawn. Therefore, this study aimed to investigate the association between AB use and the risk of fractures in patients with CKD. METHOD: This population-based cohort study used patient data obtained between April 2008 and August 2021 from a large-scale Japanese medical claims database. Consecutive patients with CKD who were newly prescribed ABs or non-AB antihypertensive drugs were included; males and females were analysed separately. The AB group was then divided into AB for HT and voiding dysfunction (VD) groups according to the drug approval in Japan. The primary outcome was the first hospitalisation due to fracture, and the variables were evaluated with weighted Cox proportional hazard model using overlap weights. RESULTS: A total of 65,012, 4,723, and 10,958 males constituted the non-AB, AB for HT (doxazosin), and AB for VD (naftopidil, silodosin, tamsulosin, or urapidil) groups, respectively. A total of 31,887, 2,409, and 965 females constituted the non-AB, AB for HT (doxazosin or guanabenz), and AB for VD (urapidil) groups, respectively. In males, hazard ratio (HR) for primary outcome was not increased in the non-AB and AB for VD groups compared with the AB for HT group (HR, 0.70; 95% confidence interval [CI], 0.38-1.28 and HR, 1.33; 95% CI, 0.67-2.66, in the non-AB and AB for VD groups, respectively). Whereas, in females, although HR for the primary outcome was not increased in the non-AB group (HR, 1.06; 95% CI, 0.56-1.99), it was significantly increased in the AB for VD group (HR, 2.28; 95% CI, 1.01-5.16) compared with the AB for HT group. CONCLUSION: AB use in patients with CKD did not increase the risk of fractures when used for the treatment of HT; however, it increased the risk of fractures when used for the treatment of VD in females. These results suggest that ABs should be used with caution in these patients.