INVESTIGATING THE LONGITUDINAL PATTERNS OF USE AND COMPARATIVE EFFECTIVENESS OF BETA BLOCKER THERAPY IN THE HEMODIALYSIS POPULATION

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  • March 20, 2019
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  • Assimon, Magdalene
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
Abstract
  • United States hemodialysis patients experience high rates of cardiovascular mortality. Approximately 50% of deaths are due to cardiovascular disease. In the general population, beta blocker treatment improves clinical outcomes in a range of cardiovascular conditions. However, the cardioprotective benefit of beta blocker therapy has never been evaluated by large randomized trials in individuals receiving maintenance hemodialysis therapy, a population with special drug dosing considerations. Pharmacologic and pharmacokinetic differences across individual beta blockers may alter drug efficacy and safety profiles in the setting of end-stage renal disease. Using the clinical research database of a large United States dialysis provider linked with the United States Renal Data system registry we assembled a cohort of maintenance hemodialysis with Medicare insurance coverage who initiated beta blocker therapy from 2007 – 2012 to: 1) assess long-term beta blocker utilization patterns in the hemodialysis population, 2) examine the association between beta blocker adherence versus non-adherence (proportion of days covered (PDC) ≥ 80% versus PDC < 80%) and all-cause mortality, and 3) evaluate the association between carvedilol versus metoprolol initiation and 1-year all-cause and cardiovascular mortality. First, we found that carvedilol and metoprolol were the most commonly initiated beta blockers (79.7% of all beta blocker new-users). After beta blocker initiation, therapy cessation (i.e. discontinuation) and re-initiation were relatively common. Second, we found that beta blocker adherence (versus non-adherence) was associated with lower all-cause mortality (PDC ≥ 80% versus < 80% measured using pharmacy claims: adjusted hazard ratio (HR) [95% confidence interval (CI)] = 0.84 [0.79, 0.90]). Finally, we found that carvedilol (versus metoprolol) initiation was associated with higher all-cause (adjusted HR [95% CI] = 1.09 [1.02, 1.16]) and cardiovascular mortality (adjusted HR [95% CI] = 1.19 [1.08, 1.30]). The potential mechanism for the observed mortality association may be the increased rate of intradialytic hypotension observed after carvedilol (versus metoprolol) initiation. Our findings provide insights into: 1) the longitudinal patterns of beta blocker utilization among individuals receiving maintenance hemodialysis therapy, 2) the association between beta blocker adherence and all-cause mortality, and most importantly, 3) provide important evidence to guide beta blocker prescribing in hemodialysis population the absence of clinical trial data.
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  • In Copyright
Advisor
  • Heiss, Gerardo
  • Flythe, Jennifer
  • Brookhart, M. Alan
  • Layton, J. Bradley
  • Fine, Jason
Degree
  • Doctor of Philosophy
Degree granting institution
  • University of North Carolina at Chapel Hill Graduate School
Graduation year
  • 2017
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