Magdalene M Assimon1, M Alan Brookhart2, Jason P Fine3, Gerardo Heiss2, J Bradley Layton4, Jennifer E Flythe5. 1. University of North Carolina Kidney Center, Division of Nephrology and Hypertension, Department of Medicine, UNC School of Medicine, Chapel Hill, NC; Department of Epidemiology, UNC Gillings School of Global Public Health, Chapel Hill, NC. Electronic address: massimon@live.unc.edu. 2. Department of Epidemiology, UNC Gillings School of Global Public Health, Chapel Hill, NC. 3. Department of Biostatistics, UNC Gillings School of Global Public Health, Chapel Hill, NC. 4. Department of Epidemiology, UNC Gillings School of Global Public Health, Chapel Hill, NC; RTI Health Solutions, Research Triangle Park, Chapel Hill, NC. 5. University of North Carolina Kidney Center, Division of Nephrology and Hypertension, Department of Medicine, UNC School of Medicine, Chapel Hill, NC; Cecil G. Sheps Center for Health Services Research, University of North Carolina, Chapel Hill, NC.
Abstract
BACKGROUND: Carvedilol and metoprolol are the β-blockers most commonly prescribed to US hemodialysis patients, accounting for ∼80% of β-blocker prescriptions. Despite well-established pharmacologic and pharmacokinetic differences between the 2 medications, little is known about their relative safety and efficacy in the hemodialysis population. STUDY DESIGN: A retrospective cohort study using a new-user design. SETTING & PARTICIPANTS: Medicare-enrolled hemodialysis patients treated at a large US dialysis organization who initiated carvedilol or metoprolol therapy from January 1, 2007, through December 30, 2012. PREDICTOR: Carvedilol versus metoprolol initiation. OUTCOMES: All-cause mortality, cardiovascular mortality, and intradialytic hypotension (systolic blood pressure decrease ≥ 20mmHg during hemodialysis plus intradialytic saline solution administration) during a 1-year follow-up period. MEASUREMENTS: Survival models were used to estimate HRs and 95% CIs in mortality analyses. Poisson regression was used to estimate incidence rate ratios (IRRs) and 95% CIs in intradialytic hypotension analyses. Inverse probability of treatment weighting was used to adjust for several demographic, clinical, laboratory, and dialysis treatment covariates in all analyses. RESULTS: 27,064 individuals receiving maintenance hemodialysis were included: 9,558 (35.3%) carvedilol initiators and 17,506 (64.7%) metoprolol initiators. Carvedilol (vs metoprolol) initiation was associated with greater all-cause (adjusted HR, 1.08; 95% CI, 1.02-1.16) and cardiovascular mortality (adjusted HR, 1.18; 95% CI, 1.08-1.29). In subgroup analyses, similar associations were observed among patients with hypertension, atrial fibrillation, heart failure, and a recent myocardial infarction, the main cardiovascular indications for β-blocker therapy. During follow-up, carvedilol (vs metoprolol) initiators had a higher rate of intradialytic hypotension (adjusted IRR, 1.10; 95% CI, 1.09-1.11). LIMITATIONS: Residual confounding may exist. CONCLUSIONS: Relative to metoprolol initiation, carvedilol initiation was associated with higher 1-year all-cause and cardiovascular mortality. One potential mechanism for these findings may be the increased occurrence of intradialytic hypotension after carvedilol (vs metoprolol) initiation.
BACKGROUND:Carvedilol and metoprolol are the β-blockers most commonly prescribed to US hemodialysis patients, accounting for ∼80% of β-blocker prescriptions. Despite well-established pharmacologic and pharmacokinetic differences between the 2 medications, little is known about their relative safety and efficacy in the hemodialysis population. STUDY DESIGN: A retrospective cohort study using a new-user design. SETTING & PARTICIPANTS: Medicare-enrolled hemodialysis patients treated at a large US dialysis organization who initiated carvedilol or metoprolol therapy from January 1, 2007, through December 30, 2012. PREDICTOR: Carvedilol versus metoprolol initiation. OUTCOMES: All-cause mortality, cardiovascular mortality, and intradialytic hypotension (systolic blood pressure decrease ≥ 20mmHg during hemodialysis plus intradialytic saline solution administration) during a 1-year follow-up period. MEASUREMENTS: Survival models were used to estimate HRs and 95% CIs in mortality analyses. Poisson regression was used to estimate incidence rate ratios (IRRs) and 95% CIs in intradialytic hypotension analyses. Inverse probability of treatment weighting was used to adjust for several demographic, clinical, laboratory, and dialysis treatment covariates in all analyses. RESULTS: 27,064 individuals receiving maintenance hemodialysis were included: 9,558 (35.3%) carvedilol initiators and 17,506 (64.7%) metoprolol initiators. Carvedilol (vs metoprolol) initiation was associated with greater all-cause (adjusted HR, 1.08; 95% CI, 1.02-1.16) and cardiovascular mortality (adjusted HR, 1.18; 95% CI, 1.08-1.29). In subgroup analyses, similar associations were observed among patients with hypertension, atrial fibrillation, heart failure, and a recent myocardial infarction, the main cardiovascular indications for β-blocker therapy. During follow-up, carvedilol (vs metoprolol) initiators had a higher rate of intradialytic hypotension (adjusted IRR, 1.10; 95% CI, 1.09-1.11). LIMITATIONS: Residual confounding may exist. CONCLUSIONS: Relative to metoprolol initiation, carvedilol initiation was associated with higher 1-year all-cause and cardiovascular mortality. One potential mechanism for these findings may be the increased occurrence of intradialytic hypotension after carvedilol (vs metoprolol) initiation.
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