Alpha blockers in CKD patients cardioprotective but may accelerate disease progression

Use of alpha blockers (ABs) in patients with chronic kidney disease (CKD) appears to be both beneficial and detrimental, with a recent study linking it to lower risk of cardiac events and mortality but higher risk of kidney disease progression compared with alternative blood pressure (BP)-lowering medications.

“Our findings suggest that further investigation into the role of AB use in CKD is warranted and that clinicians must balance these risks and benefits and provide careful monitoring when prescribing [the drug] to patients with advanced CKD,” according to Canada-based researchers from the Ottawa Hospital and University of Ottawa.

The analysis included 16,088 AB users and 16,088 matched controls who used alternative medications out of 381,120 eligible Ontario residents with hypertension. Their mean age was 76 years, and estimated glomerular filtration rate (eGFR) levels were 62 ml/min/1.73m² on average. Terazosin was the most commonly used AB (66 percent), followed by doxazosin (30 percent) and prazosin (4 percent).

In Cox proportional hazards models, AB use conferred higher risks of ≥30-percent eGFR decline (hazard ratio [HR], 1.14, 95 percent confidence interval [CI], 1.08–1.21) and dialysis/kidney transplantation (HR, 1.28, 95 percent CI, 1.13–1.44). These associations were consistent across the eGFR categories (≥90, 60-89, 30-59, <30 mL/min/1.73m²; p_interaction=0.3 for both). [Am J Kidney Dis 2020;doi:10.1053/j.ajkd.2020.07.018]

Conversely, ABs were protective against cardiac events, a benefit that was observed also across the eGFR categories (HR, 0.92, 95 percent CI, 0.89–0.95; p_interaction=0.1). Additionally, the drugs cut the risk of death, but only among patients with lower eGFR (30-59 mL/min/1.73m²: HR, 0.85, 95 percent CI, 0.78–0.93; <30 mL/min/1.73m²: HR, 0.71, 95 percent CI, 0.64–0.80; p_interaction<0.001).

In terms of safety, syncope was the only adverse event that occurred with markedly greater frequency among AB users vs nonusers in the overall population (incidence rate, 19.5 vs 15.9 events per 1,000 person-years; HR, 1.23, 95 percent CI, 1.11–1.37).

The eGFR subgroups, on the other hand, showed something different. AB use was associated with hypotension (p_interaction<0.001), and its incidence was high among patients with elevated eGFR levels but low among those with decreased eGFR.

“Our results expand upon prior studies exploring the efficacy and safety concerns attributed to AB use. Prior studies … have focused primarily on the more classic concerns related to AB use such as cardiac events and orthostatic-hypotension rather than kidney-related outcomes. Additionally, these studies have largely excluded patients with significant CKD,” the researchers noted. [JAMA 2000;283:1967-1975; Hypertension 2016;68:888-895; J Am Geriatr Soc 2018;66:679-686; Lancet 2005;366:895-906]

Understanding differential effects of ABs in CKD is more relevant than ever, the researchers asserted, especially because the drugs are commonly used to achieve BP targets in the CKD population, where hypertension is often resistant or refractory in nature. [Cochrane Database Syst Rev 2009;4:CD004643]

Given the study’s observational design and lack of BP measurement data, clinical trials are needed to establish the safety and efficacy of AB use in CKD and to shed light on the mechanisms by which AB contributes to adverse kidney outcomes, the researchers acknowledged.