Miriam E. Tucker

May 08, 2014

BOSTON — Screening all resistant-hypertensive patients for primary aldosteronism and surgically treating those who are candidates is cost-effective compared with lifelong medical therapy, a new study finds.

The results were presented in a poster here at the American Association of Endocrine Surgeons (AAES) 2014 Annual Meeting by Konstantinos P. Economopoulos, MD, PhD, a postdoctoral research fellow at Massachusetts General Hospital, Boston, and colleagues.

"The key message from this study is it's cost-effective to screen all patients with resistant hypertension for primary aldosteronism to find the subgroup of patients who require surgical treatment," Dr. Economopoulos told Medscape Medical News in an interview.

He even went so far as to suggest that screening all hypertension patients for this endocrine condition could be cost-effective but acknowledged that further trials will be needed to confirm this.

No Consensus on Screening for Primary Aldosteronism

Patients with primary aldosteronism have higher rates of stroke and myocardial infarction compared with essential-hypertension patients, and the condition is the cause of approximately 20% of cases of resistant hypertension, defined as blood pressure above goal for at least 6 months despite use of 3 antihypertensive agents, including a diuretic. Among those with primary aldosteronism, 40% have unilateral disease and can be cured with surgery, Dr. Economopolous said.

However, not all screening methods are cost-effective, and there are no consensus guidelines for primary aldosteronism screening and diagnosis, he explained.

In an analysis of 6 screening strategies, he and his colleagues found that those using the aldosterone-to-renin ratio plus either a confirmatory computed tomography (CT) scan and/or adrenal venous sampling to identify candidates for adrenalectomy resulted in gained life-years compared with lifelong mineralocorticoid-receptor–antagonist treatment, whereas use of confirmatory saline infusion testing was not cost-effective.

This study "is important and timely because of the recognized increased incidence of primary hyperaldosteronism as a cause for difficult-to-manage hypertension," said Douglas L. Fraker, MD, chief of the division of endocrine and oncologic surgery at the University of Pennsylvania Health System, Philadelphia, who was not involved in the research.

Use of Adrenal Venous Sampling Important, Despite High Costs

Dr. Economopolous and colleagues used a simulated cohort of patients with resistant hypertension, and their analysis compared aggregate intervention costs of  and change in systolic BP with the 6 screening and lateralization strategies. They all began with an aldosterone-to-renin ratio screen and then were followed by confirmatory:

  • Saline infusion testing plus CT and adrenal venous sampling.

  • CT followed by adrenal venous sampling.

  • Saline infusion testing and adrenal venous sampling

  • Adrenal venous sampling alone.

  • Saline infusion testing and CT.

  • CT alone.

Inputs for prevalence, test characteristics, treatment effects, and costs were obtained from the scientific literature. In the model, all patients were treated with either adrenalectomy or a mineralocorticoid-receptor antagonist.

Patients from the NHANES database from 2005 through 2012 sampled and entered into a cardiovascular disease model to assess comparative lifetime costs and discounted quality-adjusted life-years (QALYs) based on the intervention costs and change in systolic blood pressure with each strategy.

Results were measured against the US willingness to pay a threshold of $100,000 per QALY gained. After adjustment for health-related quality of life to account for the side effects of lifelong mineralocorticoid-receptor–antagonist treatment, the cost per QALY was just $19,400 for CT with or without adrenal venous sampling, $36,400 for CT only, and $101,900 for adrenal venous sampling only.

Based on published data, the expected reduction in the systolic BP after adrenalectomy is approximately 30 mm Hg. When the investigators ranged the systolic BP reduction from 20 to 40 mm Hg, the same strategies remained cost-effective, although cost per QALY for adrenal venous sampling alone reached as high as $266,000.

Dr. Economopolous said the reason CT plus adrenal venous sampling if needed works out to be much cheaper than adrenal venous sampling alone, or even CT alone, is because it is very accurate in helping determine who is best suited to surgery and who is not.

Dr. Fraker told Medscape Medical News that his group and others have demonstrated that results of adrenal venous sampling will change surgical management in up to 25% of cases of false-positive or false-negative CTs.

"Most high-volume centers routinely recommend adrenal venous sampling for any patient older than 40 years and for patients under 40 without a clear mass," he said.

"Patients may have a nonfunctional adrenal adenoma but really have bilateral hyperplasia as the cause for [hyperaldosteronism], and this would be a false-positive CT scan. On the other hand, patients may not have a mass by CT, and adrenal venous sampling may strongly lateralize due to a small aldosteronoma not imaged or unilateral hyperplasia. This situation would be a false-negative CT scan."

Should All Hypertension Patients Be Screened for Aldosteronism?

Dr. Economopoulos said the "robustness" of his overall results imply that screening all newly diagnosed hypertensive patients — not just those with resistant hypertension — might also be cost-effective.

This is because "there are primary-hyperaldosteronism patients with unilateral disease and a systolic BP greater than 160 mm Hg who can be treated with surgery and avoid being on at least 3 different hypertensive medications for a lifetime," he observed.

But if this is not possible or likely for all patients with hypertension, a cost benefit might be found for testing all who are over a certain age or who have a family history of cardiovascular disease, he added. "Nobody believed it would be the case for resistant hypertension, so who knows….This is a hypothesis that needs to be tested in future research studies."

Dr. Economopolous and Dr. Fraker have reported no relevant financial relationships.

American Association of Endocrine Surgeons (AAES) 2014 Annual Meeting; April 27, 2014; Boston, Massachusetts. Poster 6.


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