Blood Pressure Control with Alpha-Blockers in Patients with CKD

There is a high prevalence of chronic kidney disease (CLD) among older patients; more than 20% of individuals ≥65 years of age are affected by CKD and have high rates of morbidity, mortality, and use of healthcare resources. Hypertension is nearly ubiquitous among patients with CKD; hypertension prevalence is >80%. Cardiac outcomes are improved with adequate blood pressure control in patients with CKD, who, on average, require two to four blood pressure lowering mediations to achieve recommended targets.

Alpha-blockers (ABs) reduce blood through competitive inhibition of postsynaptic  a1-adrenoreceptors of vascular smooth muscle, resulting in vasodilation of veins and arterioles and a decrease in peripheral vascular resistance.  Due to concerns about safety, ABs are considered add-on therapy for resistant or refractory hypertension. However, they are commonly prescribed due to their effectiveness.

There are few data available on the association between AB use and kidney, cardiac, and safety outcomes in patients with CKD. Gregory L. Hundemer, MD, MPH, and colleagues conducted a population-based retrospective cohort study to examine whether the association of AB use and kidney disease progression, cardiac events, all-cause mortality, and safety-related events (hypotension, syncope, falls, and fractures) varied by CKD stage compared with non-AB blood pressure lowering medications. Results of the study were reported in the American Journal of Kidney Diseases [2021;77(2):178-189].

The study exposure was new use of an AB versus new use of a non-AB blood pressure lowering medication. The primary outcomes of interest were ≥30% decline in estimated glomerular filtration rate (eGFR); kidney replacement therapy (initiation of dialysis or kidney transplantation); a composite of acute myocardial infarction, coronary revascularization, congestive heart failure, or atrial fibrillation; safety events; and mortality.

The study utilized data on older adults (≥66 years of age) treated for hypertension from 2007 to 2015 in Ontario, Canada. Demographics and viral status data were obtained from the Ontario Registered Persons Database; medication data were obtained from the Ontario Drug Benefit Claims database.

A total of 381,120 eligible Ontario residents were diagnosed with hypertension during the study period. Of those, 4% (n=16,511) were prescribed an AB. A total of 16,088 of those patients were matched 1:1 to patients prescribed non-AB blood pressure lowering medications. Prematching, compared with the non-AB group the AB group had a higher proportion of men, lower eGFR, higher prevalence of diabetes and use of glucose-lowering medications, and higher statin use. Following matching, the two groups were similar in those characteristics.

Mean patient age was 76 years and mean eGFR was 62 mL/min/1.73 m2. Following matching, there was no detectable difference between the two groups with the exception of a minor imbalance in the rates of nephrology care. The most commonly prescribed AB was terazosin (66%), followed by doxazosin (30%) and prazosin (4%). The most commonly prescribed non-AB blood pressure lowering medications at index date were angiotensin receptor blockers (28%), beta blockers (23%), and calcium channel blockers (18%).

Overall, there was an association between AB use and a higher risk for ≥30% greater decline, compared with non-AB use (121 vs 107 events/1000 person-years; hazard ratio [HR], 1.14; 95% confidence interval [CI], 1.08-1.21). There was also an association between AB use and higher risk for dialysis or kidney transplantation compared with non-AB use (15.2 vs 11.4 events/1000 person years; HR, 1.28; 95% CI, 1.13-1.44). A small number of kidney replacement therapy events occurred in patients with eGFR ≥60 mL/min/1.73 m2 (AB group, 45 events; non-AB group, 47 events) compared with patients with eGFR <60 mL/min/1.73 m2 (AB group, 597 events; non-AB group, 428 events).

For the total population, there was an association between AB use and lower risk for cardiac events compared with non-AB use (207 vs 224 events/1000 person-years; HR, 0.92; 95% CI, 0.89-0.95).  There was also an association between AB use and lower all-cause mortality risk compared with non-AB use (60.7 vs 67.6 events/1000 person-years; HR, 0.89; 95% CI, 0.84-0.94).

Among patients with eGFR <30 mL/min/1.73 m2, there was an association between AB use and a 29% reduction in morality risk (138 vs 195 events/1000 person-years; HR, 0.71; 95% CI, 0.64-0.80). Among patients with eGFR 30 to 59 mL/min/1.73 m2, AB use was associated with a 15% reduction in mortality risk (73.0 vs 85.7 events/1000 person-years; HR, 0.85; 95% CI, 0.78-0.93). The difference in risk between AB and non-AB users was nonsignificant among patients with eGFR ≥60 mL/min/1.73 m2.

For the total population, the only safety-related event that was found to have an increased association with AB use compared with non-AB use was syncope (19.5 vs 15.9 events/1000 person-years; HR, 1.23; 95% CI, 1.11-1.37). The only safety-related outcome in which effect modification between eGFR and AB use was present was hypotension (P for interaction ≤.001), with AB use generally associating with higher risk for hypotension among those with higher eGFR and lower risk for hypotension among those with lower eGFR.

The researchers cited some limitations to the study including the observational design, the lack of data on blood pressure measurements, and missing data on frailty, medication intolerances, side effects, and allergies.

The researchers said, “In conclusion, AB use in older patients with CKD is associated with more rapid decline in kidney function but lower risks for cardiac events and all-cause mortality. These disparate results demonstrate the need for clinical trials to assess the safety and efficacy of AB use in CKD. We suggest that close monitoring of eGFR in patients using ABs is warranted and caution should be exercised when initiating a patient with CKD on AB therapy. Future prospective studies are needed to further understand the mechanisms by which AB therapy contributes to adverse kidney outcomes.”

Takeaway Points

  1. Associations between use of alpha-blockers (ABs) to control resistant or refractory hypertension in patients with chronic kidney disease are largely unknown.
  2. Results of a population-based retrospective cohort study found an association between use of ABs and a higher risk for adverse kidney outcomes, including kidney disease progression.
  3. There was an association between AB use and lower risk of cardiac events across all categories of estimated glomerular filtration rate.