Physicians in denial; side effects of MRAs may deter prescribing
A second big cause of low PA testing rates is that doctors make the mistake of thinking a PA test result won’t change how they manage these patients.
The established treatment for most patients with treatment-resistant hypertension as well as PA is adding an MRA, either spironolactone or eplerenone (Inspra).
Many providers cling to the belief that they will start an MRA in these patients without first determining their PA status, says Dr. Cohen, but the data she and her colleagues collected show the opposite.
Overall, about 13% of all patients in the study began treatment with an MRA during follow-up. The likelihood of starting treatment with this drug class was fourfold higher among the patients tested for PA compared with those who were not tested.
PA testing also hastened the start of MRA use by more than a year, compared with untested patients.
“Providers think they prescribe an MRA” to treatment-resistant patients, “but it’s part of their denial. They are not using the evidence-based treatments [spironolactone or eplerenone], perhaps because of concerns about MRA side effects, although those have been pretty well overcome during the past 20 years,” she observed.
Dr. Cohen says gynecomastia is one adverse effect that gives pause to VHA clinicians who see a heavily male patient population. “It’s probably the biggest concern and why PA testing and MRA use is low” in the VHA system, she said.
“You can use a lower dosage of spironolactone, and the incidence is less common with eplerenone,” although using eplerenone does not completely eliminate all gynecomastia cases, she noted.
At the University of Pennsylvania hospitals, men often start on spironolactone first because it retains a significant price advantage, even though eplerenone is now generic, but “if there is a hint of gynecomastia, we quickly switch to eplerenone, which is usually well tolerated,” she explained.
And while eplerenone has a reputation of being less effective than spironolactone, “I’ve prescribed a lot of eplerenone and have had good results,” Dr. Cohen said. “Even if the blood pressure lowering is not as great compared with spironolactone, it still blunts the toxic effects of aldosterone on target organs.”
Hyperkalemia is the other big concern about spironolactone and eplerenone. Both agents cause it at roughly the same rate, although the rate is lower in patients without chronic kidney disease.
A new, nonsteroidal MRA, finerenone, caused substantially less hyperkalemia in a recent phase 3 trial, FIDELIO-DKD, and as a nonsteroidal MRA, it does not cause gynecomastia. Finerenone has promise as a potentially safer option for treating PA and treatment-resistant hypertension, noted Cohen, but so far, no advanced clinical trials have been launched to examine its efficacy for these indications.
PA testing allows a surgical option
A third reason to test patients with treatment-resistant hypertension for PA is that jumping straight to MRA treatment denies the patient assessment for a unilateral adrenal adenoma as the cause of excess aldosterone.
When unilateral adenomas exist, patients are candidates for adrenalectomy. Despite the potential advantage this gives patients to eliminate the cause of their PA without the need for additional drug treatment, some clinicians don’t see this as a compelling rationale to test for PA because they have a bias against surgery or have seen too many cases in which surgery failed to produce full hypertension resolution.
“It’s all about setting expectations appropriately” for the impact of this surgery, Dr. Cohen said.
“Adrenalectomy is not a cure; it just gets rid of the source of excess aldosterone.” But in patients with long-standing PA and hypertension, this is often not enough to completely resolve entrenched cardiovascular pathology.
PCPs, cardiologists in rural locations least likely to order PA testing
Of the 269,010 patients analyzed by Dr. Cohen and her coauthors, the average age was 65 years; 96% were men; half were obese; and 40% had diabetes. The researchers excluded patients who had already been tested for PA, as well as those who were already receiving treatment with an MRA.
For 88% of the patients, the main physician overseeing care was a PCP. A cardiologist was the main physician for 10%; a nephrologist, for 1%; and an endocrinologist, for fewer than 1%.
The rate of testing for PA varied across the 130 VHA centers that contributed data, ranging from 0% to 6%. The testing data showed that endocrinologists were most likely to order PA testing, doing it 2.48-fold more often than PCPs. Nephrologists were roughly twice as likely to order PA testing than PCPs, and cardiologists ordered testing at about the same rate as PCPs.
Patients managed at VHA centers in rural locations were nearly half as likely to undergo testing as patients managed at nonrural centers. The number of patients with treatment-resistant hypertension seen by a physician or at a center had no significant relationship to PA testing frequency.
The study received no commercial funding. Dr. Cohen has disclosed no relevant financial relationships.
A version of this story first appeared on Medscape.com.