Kidney, Cardiac, and Safety Outcomes Associated With α-Blockers in Patients With CKD: A Population-Based Cohort Study.

Abstract

RATIONALE & OBJECTIVES:

Alpha-blockers (ABs) are commonly prescribed for control of resistant or refractory hypertension in patients with and without chronic kidney disease (CKD). The association between AB use and kidney, cardiac, mortality, and safety-related outcomes in CKD remains unknown.

STUDY DESIGN:

Population-based retrospective cohort study.

SETTINGS & PARTICIPANTS:

Ontario (Canada) residents 66 years and older treated for hypertension in 2007 to 2015 without a prior prescription for an AB.

EXPOSURES:

New use of an AB versus new use of a non-AB blood pressure (BP)-lowering medication.

OUTCOMES:

30% or greater estimated glomerular filtration rate (eGFR) decline; dialysis initiation or kidney transplantation (kidney replacement therapy); composite of acute myocardial infarction, coronary revascularization, congestive heart failure, or atrial fibrillation; safety (hypotension, syncope, falls, and fractures) events; and mortality.

ANALYTICAL APPROACH:

New users of ABs (doxazosin, terazosin, and prazosin) were matched to new users of non-ABs by a high dimensional propensity score. Cox proportional hazards and Fine and Gray models were used to examine the association of AB use with kidney, cardiac, mortality, and safety outcomes. Interactions by eGFR categories (≥90, 60-89, 30-59, and<30mL/min/1.73m2) were explored.

RESULTS:

Among 381,120 eligible individuals, 16,088 were dispensed ABs and matched 1:1 to non-AB users. AB use was associated with higher risk for≥30% eGFR decline (HR, 1.14; 95% CI, 1.08-1.21) and need for kidney replacement therapy (HR, 1.28; 95% CI, 1.13-1.44). eGFR level did not modify these associations, P interaction=0.3and 0.3, respectively. Conversely, AB use was associated with lower risk for cardiac events, which was also consistent across eGFR categories (HR, 0.92; 95% CI, 0.89-0.95; P interaction=0.1). AB use was also associated with lower mortality risk, but only among those with eGFR<60mL/min/1.73m2 (P interaction<0.001): HRs were 0.85 (95% CI, 0.78-0.93) and 0.71 (95% CI, 0.64-0.80) for eGFR of 30 to 59 and<30mL/min/1.73m2, respectively.

LIMITATIONS:

Observational design, BP measurement data unavailable.

CONCLUSIONS:

AB use in CKD is associated with higher risk for kidney disease progression but lower risk for cardiac events and mortality compared with alternative BP-lowering medications.

• Authors: Gregory L Hundemer, Greg A Knoll, William Petrcich, Swapnil Hiremath, Marcel Ruzicka, Kevin D Burns, Cedric Edwards, Ann Bugeja, Emily Rhodes, Manish M Sood
• Journal: American journal of kidney diseases : the official journal of the National Kidney Foundation (Am J Kidney Dis) Vol. 77 Issue 2 Pg. 178-189.e1 (02 2021) ISSN: 1523-6838 [Electronic] United States
• PMID: 32920153 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Chemical References

• Adrenergic alpha-Antagonists
• Antihypertensive Agents
• Terazosin
• Doxazosin
• Prazosin

Topics

• Accidental Falls (statistics & numerical data)
• Adrenergic alpha-Antagonists (therapeutic use)
• Aged
• Aged, 80 and over
• Antihypertensive Agents (therapeutic use)
• Atrial Fibrillation (epidemiology)
• Cohort Studies
• Disease Progression
• Doxazosin (therapeutic use)
• Female
• Fractures, Bone (epidemiology)
• Glomerular Filtration Rate
• Heart Failure (epidemiology)
• Humans
• Hypertension (complications, drug therapy)
• Hypotension (chemically induced)
• Kidney Failure, Chronic (epidemiology, therapy)
• Male
• Mortality
• Myocardial Infarction (epidemiology)
• Myocardial Revascularization (statistics & numerical data)
• Ontario (epidemiology)
• Prazosin (analogs & derivatives, therapeutic use)
• Propensity Score
• Proportional Hazards Models
• Renal Insufficiency, Chronic (complications, metabolism)
• Renal Replacement Therapy (statistics & numerical data)
• Retrospective Studies
• Syncope (chemically induced)