Risk of fractures in subjects with antihypertensive medications: A nationwide claim study

Background: The effect of antihypertensives on fracture has important clinical implications, since antihypertensives are frequently prescribed with lifelong exposure. This study aimed to compare risk of fracture between antihypertensive medication classes and non-users among adults. Methods: Nationwide claim data from January 1, 2007 to December 31, 2011 were analyzed. Among 8,315,709 subjects with antihypertensive prescriptions in nation wide medical claim database in South Korea, 528,522 subjects, who initiated single-drug antihypertensives or non-users, were analyzed. Subjects were classified as non-user, alpha-blocker (AB), angiotensin-converting-enzyme-inhibitor (ACEI), angiotensin-receptor-blocker (ARB), beta-blocker (BB), calcium-channel-blocker (CCB), and diuretic users. Subjects with combination antihypertensive medications were excluded. Results: A total of 16,805 fracture outcomes were observed during mean follow-up duration of 1.9 years. Fracture rate per 10,000 person-years varied significantly across type of antihypertensives, with ARB having the lowest rate (152.7, 95% confidence interval (CI) 145.4-160.4), and AB having the highest rate (323.7, 95% CI 237.4-441.4). Non-users had fracture rates (152.2, 95% CI 148.7-155.7) similar to ARB users. In models adjusting for age, gender, comorbidity score, diagnosis of diabetes, diagnosis of osteoporosis, osteoporosis treatment, and osteoporosis related diseases, AB users (adjusted hazard ratio (aHR) = 2.26), ACEI users (aHR = 1.68), diuretic users (aHR = 1.45), CCB users (aHR = 1.23), and BB users (aHR = 1.15) showed significantly increased risk of fractures compared with non-users (P < 0.05). Only the fracture risk of ARB users (aHR = 1.00, 95% CI 0.95-1.05) was not significantly different from the non-users. Conclusions: The use of antihypertensives except for ARB is associated with increased risk of fracture, with ACEI and AB having higher risk among hypertensive adults. (C) 2015 Elsevier Ireland Ltd. All rights reserved.