Kidney, cardiac, and safety outcomes associated with α-blockers in patients with CKD: a population-based cohort study
Hundemer GL, Knoll GA, Petrcich W, Hiremath S, Ruzicka M, Burns KD, Edwards C, Bugeja A, Rhodes E, Sood MM. Am J Kidney Dis. 2021; 77(2):178-89.e1. Epub 2020 Sep 10. DOI: https://doi.org/10.1053/j.ajkd.2020.07.018
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 old treated for hypertension between 2007 and 2015 without a prior prescription for an AB.
Exposures — New use of an AB versus new use of a non-AB BP-lowering medication.
Outcomes — ≥30% eGFR decline, dialysis initiation or kidney transplantation, composite of acute myocardial infarction, coronary revascularization, congestive heart failure, or atrial fibrillation, safety (hypotension, syncope, falls, fractures) events, and mortality
Analytical Approach — New users of AB (doxazosin, terazosin, prazosin) were matched to new users of non-AB 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, <30 mL/min/1.73m 2) 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 a higher risk of ≥30% eGFR decline (HR 1.14 [95%CI 1.08-1.21]) and need for dialysis/kidney transplantation (HR 1.28 [95%CI 1.13-1.44]). Level of eGFR did not modify these associations, p-interaction = 0.3 and 0.3, respectively. Conversely, AB use was associated with a lower risk of cardiac events, which was also consistent across eGFR categories (HR 0.92 [95%CI 0.89-0.95]; p-interaction = 0.1). AB was also associated with a lower mortality risk, but only among those with lower eGFR <60 mL/min/1.73m 2, (p-interaction <0.001): HR 0.85 [95%CI 0.78-0.93] for eGFR 30-59 mL/min/1.73m 2; HR 0.71 [95%CI 0.64-0.80] for eGFR<30 mL/min/1.73m 2).
Limitations — Observational design, BP measurement data unavailable
Conclusions — AB use in CKD is associated with a higher risk of kidney disease progression but a lower risk for cardiac events and mortality compared with alternative BP-lowering medications.