Risk of Osteoporotic Fractures With Angiotensin II Receptor Blockers Versus Angiotensin-Converting Enzyme Inhibitors in Hypertensive Community-Dwelling Elderly

Abstract

Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) are used to treat hypertension; however, in vivo and clinical studies suggest that ARBs and ACE inhibitors may exert different effects on bone. The association between long-term use of ARBs and ACE inhibitors and fracture requiring medical attention is limited. We conducted a population-based, retrospective cohort study with propensity score matching using administrative databases in Ontario, Canada, to examine the risk of osteoporosis-related fractures in hypertensive elderly treated with ARBs versus ACE inhibitors. We identified a cohort of newly treated hypertensive patients aged 66 years and older who initiated an ACE inhibitor from May 1, 2004, to March 31, 2012, and matched them to ARB users on propensity score, sex, and age at drug initiation. The primary outcome was hip fracture, and secondary outcomes were non-hip major osteoporotic fractures (other femoral, clinical vertebral, forearm, wrist, humerus) and other osteoporotic fractures (pelvis, clavicle, patella, shoulder, upper arm, tibia, fibula, ankle, scapula, ribs, sternum, trunk). We calculated hazard ratios (HRs) using Cox proportional hazards model with robust standard errors. Of the 87,635 patients who initiated treatment, 28,819 (32.9%) started ARBs and 58,816 (67.1%) started ACE inhibitors. Among new ARB users, 27,815 (96.5%) were successfully matched to ACE inhibitor users. Without dose adjustment, no significant association was observed for ARBs relative to ACE inhibitor users for hip fractures (HR = 0.88; 95% confidence interval [CI] 0.70-1.11), with a decreased risk of other major osteoporotic fractures (HR = 0.81; CI 0.70-0.93) and no significant association for other osteoporotic fractures (HR = 0.88; CI 0.74-1.05). When adjusted for dosage, there was no significant difference between the effects of ARBs and ACE inhibitors on hip (HR = 0.99; CI 0.78-1.25), other major osteoporotic (HR = 0.87; CI 0.75-1.01), and other osteoporotic fractures (HR = 0.90; CI 0.74-1.08).