Outcomes in Unilateral Primary Aldosteronism After Surgical or Medical Therapy

Troy H. Puar; Lih M. Loh; Wann J. Loh; Dawn S. T. Lim; Meifen Zhang; Pei T. Tan; Lynette Lee; Du S. Swee; Joan Khoo; Donovan Tay; Sarah Y. Tan; Ling Zhu; Linsey Gani; Thomas F. King; Peng C. Kek; Roger S. Foo

Disclosures

Clin Endocrinol. 2021;94(2):158-167. 

In This Article

Abstract and Introduction

Abstract

Context: Studies find surgery superior to medications in the treatment of primary aldosteronism (PA). It would be ideal to compare surgical and medical therapy in patients with unilateral PA only, who have the option between these treatment modalities. However, this is challenging as most patients with unilateral PA on adrenal vein sampling (AVS) undergo surgery.

Objective: To compare outcomes of surgery and medications in patients with confirmed or likely unilateral PA.

Design: Retrospective cohort study of 274 patients with PA managed at two referral centres from 2000 to 2019.

Patients: 154 patients identified with unilateral PA using AVS and a validated clinical prediction model were treated with surgical (n = 86) or medical (n = 68) therapy.

Measurements: Primary outcome was a composite incident cardiovascular event comprising acute myocardial infarction, coronary revascularization, stroke, atrial fibrillation or congestive cardiac failure. Secondary outcomes were clinical and biochemical control.

Results: Cardiovascular outcomes were comparable, with the surgery group having an adjusted hazard ratio of 0.93 (95% CI: 0.32–2.67), p = .89. Both treatments improved clinical and biochemical control, but surgery resulted in better systolic blood pressure, 133.0 ± 11.7 mmHg versus 137.9 ± 14.6 mmHg, p = .02, and lower defined daily dosages of antihypertensive medications, 1.0 (IQR 0.0–2.0) versus 2.6 (IQR 0.8–4.3), p < .001. In addition, 12 of 86 patients in the surgery group failed medical therapy before opting for surgery.

Conclusion: In patients with unilateral PA who can tolerate medications, medical therapy improves clinical and biochemical control, and may offer similar cardiovascular protection. However, surgery reduces pill burden, may cure hypertension and is recommended for unilateral PA.

Introduction

Primary aldosteronism (PA) is likely the most common treatable cause of hypertension, afflicting 5%–20% of all patients with hypertension.[1,2] Patients with PA are at higher risk of myocardial infarctions, strokes and atrial fibrillation when compared to patients with essential hypertension at similar levels of blood pressure (BP).[3,4] This has been attributed to the direct deleterious effects of aldosterone.[4,5] Specific treatment of PA improves BP control and may ameliorate this excess cardiovascular risk.[4,5] While some studies have shown that medical or surgical therapy have similar benefits in terms of BP, cardiovascular and renal outcomes,[5,6] others have found surgery to be superior.[7] Of note, a recent large retrospective study found that while surgery led to reduced cardiovascular events, patients treated with medical therapy had persistently elevated risk.[8,9] This suggests that surgery is a superior therapeutic option for patients with PA.

However, studies comparing surgical and medical therapy are often confounded by the fact that patients undergoing either treatment have two distinctly different underlying pathologies.[4,8,10] Surgically treated patients have unilateral PA, while medically treated patients often have bilateral PA. While somatic mutations have been found in ~50% of adrenal tumours from patients with unilateral PA,[11,12] the mechanisms underpinning bilateral PA is still largely unknown. Since surgery can only be considered in unilateral PA, it would be more appropriate to compare the outcomes of surgery versus medical therapy in only patients with unilateral PA. However, this direct comparison is challenging. Prior to surgery, almost all patients with PA are required to undergo an invasive adrenal vein sampling (AVS) to confirm unilateral disease. AVS is not necessary if patients are not keen for surgery. Hence, the majority of patients with confirmed unilateral PA after AVS opt for surgery instead of medical therapy, making such a comparison between the two modalities difficult. Meanwhile, many patients on medical therapy without a prior AVS result may have underlying unilateral disease. These patients form an ideal comparison cohort. Therefore, we adopted a novel approach of applying a recently validated prediction score that our group had developed, to identify these patients with unilateral PA.

This clinical prediction score, the aldosterone–potassium ratio (APR), was recently developed in our Asian cohort and validated externally in a European cohort. It was highly accurate in differentiating patients with unilateral PA from those with bilateral PA,[13] with an area under receiver-operating characteristic curve of 0.80 (95% CI: 0.70–0.89). APR is calculated using the baseline aldosterone (ng/dl) divided by lowest-recorded potassium, and patients with elevated APR are more likely to have unilateral PA. Hence, we applied our prediction score to patients without a formal AVS result, to identify those with likely unilateral PA, in addition to those identified by lateralization on AVS. Subsequent analyses were performed to compare the outcomes between surgical and medical therapy for these patients with unilateral PA.

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