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Primary Aldosteronism and the Role of Mineralocorticoid Receptor Antagonists for the Heart and Kidneys.

ABSTRACT: Primary aldosteronism (PA) is the most common cause of secondary hypertension but is frequently underrecognized and undertreated. Patients with PA are at a markedly increased risk for target organ damage to the heart and kidneys. While patients with unilateral PA can be treated surgically, many patients with PA are not eligible or willing to undergo surgery. Steroidal mineralocorticoid receptor antagonists (MRAs) are highly effective for treating PA and reducing the risk of target organ damage. However, steroidal MRAs are often underprescribed and can be poorly tolerated by some patients due to side effects. Nonsteroidal MRAs reduce adverse renal and cardiovascular outcomes among patients with diabetic kidney disease and are bettertolerated than steroidal MRAs. While their blood pressure-lowering effects remain unclear, these agents may have a potential role in reducing target organ damage in patients with PA.

SUBMITTER: Cohen JB

PROVIDER: S-EPMC9892285 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Primary Aldosteronism and the Role of Mineralocorticoid Receptor Antagonists for the Heart and Kidneys.

Cohen Jordana B JB Bancos Irina I Brown Jenifer M JM Sarathy Harini H Turcu Adina F AF Cohen Debbie L DL

Annual review of medicine 20221114

Primary aldosteronism (PA) is the most common cause of secondary hypertension but is frequently underrecognized and undertreated. Patients with PA are at a markedly increased risk for target organ damage to the heart and kidneys. While patients with unilateral PA can be treated surgically, many patients with PA are not eligible or willing to undergo surgery. Steroidal mineralocorticoid receptor antagonists (MRAs) are highly effective for treating PA and reducing the risk of target organ damage. ...[more]

PMID: 36375469

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Project description:AimsTo determine the incidence of hyperkalaemia in patients with heart failure with reduced ejection fraction (HFrEF) during up-titration of guideline-directed medical therapy (GDMT) in real-world settings.MethodsA retrospective review of medical records of all patients hospitalized for newly onset HFrEF at Sahlgrenska University Hospital, Sweden, between 1 January 2016 and 31 December 2019. Based on mineralocorticoid receptor antagonist (MRA) treatment within the first 6 months, patients were divided into four groups: (i) never received MRA, (ii) needed MRA dose reduction, (iii) needed discontinuation of MRA, and (iv) stable MRA treatment. Potassium levels were assessed at baseline and has the highest potassium level during the 6 months of up-titration.ResultsOf 3456 patients hospitalized for heart failure, 630 (18%) were eligible (68.4% men, 66.8 years, mean EF of 29.4%). After up-titration of GDMT 48.4% of patients received MRAs. Patients without MRA treatment were older (P < 0.0001), had lower EF (P = 0.022), had higher NTproBNP (P = 0.017), had lower eGFR (P = 0.001), and were more often treated with angiotensin receptor inhibitors/angiotensin receptor blockers/angiotensin receptor neprilysin inhibitors (all P < 0.0001). In overall study population, hyperkalaemia increased from 5.9 to 24.4% after 6 months of up-titration of GDMT (P < 0.0001). Among four groups, the incidence of hyperkalaemia throughout up-titration of GDMT increased from 6.8 to 54.5% in patients with dose reduction of MRA, from 8.8 to 50.9% in those with discontinuation of MRA, from 5 to 10% in patients with stable MRA treatment, and from 6 to 28% in patients who were MRA naive (all P < 0.0001). In the MRA-naive group, normokalaemia/hypokalaemia occurred in 87.5% at baseline, and after 6 months of up-titration of GDMT, normokalaemia/hypokalaemia remained in 47.8%, whereas mild, moderate, and severe hyperkalaemia occurred in 22.4%, 5.7%, and 0.9%, respectively.ConclusionsHyperkalaemia increased significantly during up-titration of GDMT but with varying magnitudes in different clinical phenotypes, which might explain why physicians refrain from prescribing MRAs to patients with HFrEF.

Project description:BackgroundPrimary aldosteronism is a common cause of treatment-resistant hypertension. However, evidence from local health systems suggests low rates of testing for primary aldosteronism.ObjectiveTo evaluate testing rates for primary aldosteronism and evidence-based hypertension management in patients with treatment-resistant hypertension.DesignRetrospective cohort study.SettingU.S. Veterans Health Administration.ParticipantsVeterans with apparent treatment-resistant hypertension (n = 269 010) from 2000 to 2017, defined as either 2 blood pressures (BPs) of at least 140 mm Hg (systolic) or 90 mm Hg (diastolic) at least 1 month apart during use of 3 antihypertensive agents (including a diuretic), or hypertension requiring 4 antihypertensive classes.MeasurementsRates of primary aldosteronism testing (plasma aldosterone-renin) and the association of testing with evidence-based treatment using a mineralocorticoid receptor antagonist (MRA) and with longitudinal systolic BP.Results4277 (1.6%) patients who were tested for primary aldosteronism were identified. An index visit with a nephrologist (hazard ratio [HR], 2.05 [95% CI, 1.66 to 2.52]) or an endocrinologist (HR, 2.48 [CI, 1.69 to 3.63]) was associated with a higher likelihood of testing compared with primary care. Testing was associated with a 4-fold higher likelihood of initiating MRA therapy (HR, 4.10 [CI, 3.68 to 4.55]) and with better BP control over time.LimitationsPredominantly male cohort, retrospective design, susceptibility of office BPs to misclassification, and lack of confirmatory testing for primary aldosteronism.ConclusionIn a nationally distributed cohort of veterans with apparent treatment-resistant hypertension, testing for primary aldosteronism was rare and was associated with higher rates of evidence-based treatment with MRAs and better longitudinal BP control. The findings reinforce prior observations of low adherence to guideline-recommended practices in smaller health systems and underscore the urgent need for improved management of patients with treatment-resistant hypertension.Primary funding sourceNational Institutes of Health.

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Primary Aldosteronism and the Role of Mineralocorticoid Receptor Antagonists for the Heart and Kidneys.

Publications

Primary Aldosteronism and the Role of Mineralocorticoid Receptor Antagonists for the Heart and Kidneys.

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