Abstract
Importance: Alpha- blockers (AB) are commonly prescribed agents in the treatment of hypertension. Little is known regarding the risk of hypotension and hypotension-related clinical outcomes in patients with advanced age with ongoing treatment for hypertension. Objective: To assess the risk of hypotension and hypotension-related adverse events (syncope, falls, fractures), major adverse cardiac events and all-cause mortality with AB use compared to other anti-hypertensives. Methods: Population-based, retrospective cohort study of 933,033 eligible adults of advanced age (> 66 years) prescribed an anti-hypertensive medication between 1995 and 2015 in Ontario, Canada. A high dimensional propensity score was used to match AB prescription to other anti-hypertensives. AB exposure was modeled as a time-varying and cumulative covariate using extended, conditional Cox proportional hazards to examine the association with outcomes. Primary outcome was hospitalization or emergency room usage for hypotension and related complications (syncope, fractures, falls). Secondary outcomes included major adverse cardiovascular events and all-cause mortality. Results: Among 69,092 matched patients prescribed AB, the incident rate of hypotension related complications were higher compared to other anti-hypertensives (hypotension 1.15 vs. 0.39, syncope 1.47 vs. 0.46, falls 4.37 vs. 1.37, fractures 2.23 vs. 0.69 per 100 person-years of follow-up). In time-varying exposure models with additional adjustment for the total number of anti-hypertensives, the higher risk persisted (hypotension HR 1.34 95%CI 1.26-1.43, syncope HR 1.49 95%CI 1.41-1.57, falls HR 1.27 95%CI 1.23-1.32, HR fractures 1.41 95%CI 1.34-1.48). Secondary outcomes of MACE and all-cause mortality were higher or similar among AB users (MACE IR 7.03 vs. 2.31, mortality 6.54 vs 6.37 per 100 person-years follow-up). The risk was highest among those > 85 and differed by the number of total anti-hypertensives prescribed. Conclusions: The use of AB is associated with a higher risk of hypotension-related events and other complications. Our findings suggest other anti-hypertensive agents be considered especially among those of advanced age or based on the number of total anti-hypertensive agents.
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