Side effects limit long-term therapy for primary aldosteronism

Long-term medical therapy in patients with primary aldosteronism (PA) is held back by dose-dependent side effects, according to a recent Singapore study.

“We found in our large cohort of patients with PA treated with long-term medications that although a large majority achieved normokalaemia without potassium supplementation, only about half achieved clinical control of hypertension or biochemical control,” the researchers said. “Fifty-two percent of patients experienced side effects to medications, which resulted in dose reduction or cessation of medications in a third of patients.”

The retrospective analysis included 201 PA patients who were on follow-up at the Changi General Hospital and Singapore General Hospital from 2000 to 2020. Participants were being treated with spironolactone, eplerenone, or amiloride. Outcomes included clinical control (blood pressure [BP] <140/90 mm Hg), biochemical control (serum potassium ≥4.3 mmol/L and plasma renin activity [PRA] >1 ng/mL/h) and side effects.

Majority of patients on long-term medical therapy achieved normokalaemia (90.1 percent), while BP control to <140/90 mm Hg was documented in 57.4 percent. Forty-eight percent reached potassium ≥4.3 mmol/L, while the PRA benchmark was achieved by 63.2 percent of patients who had the appropriate measurements. [J Endocr Soc 2021;5:bvab144]

Biochemical control, defined according to both potassium and renin biomarkers, was documented in 49.1 percent of participants.

The rates of clinical response were comparable between patients with unilateral vs bilateral PA, even when assessed in terms of the absolute decline in systolic and diastolic BP. The same was true for serum potassium and PRA, and persistent hypokalaemia.

In terms of tolerability, 52.3 percent of participants experienced at least one adverse event. Side effects were significantly more common in unilateral PA patients (63.2 percent vs 41.8 percent; p=0.008) as well as in spironolactone vs eplerenone and amiloride users (49.8 percent vs 3.8 percent and 9.1 percent; p<0.001). Adverse events were also more frequent in men (59.2 percent vs 38.5 percent; p=0.015).

Moreover, adverse events became more common the longer patients were on medical therapy: 57.9 percent of patients being treated for >12 months developed side effects as opposed to only 27.6 percent of those treated for ≤12 months (p<0.003). Such side effects led to dose reductions in 25.0 percent, change of medication in 11.4 percent, and total cessation of therapy in 12.9 percent.

“Although medical therapy improves hypertension and biochemical control in patients with PA, side effects are common, and this can limit the overall efficacy of medications. Alternatives to current medical therapy options may help to address this,” the researchers said.

“Future prospective studies should assess the best monitoring strategy for biochemical control during long-term medical therapy,” they added.