Mineralocorticoid receptor antagonists in adults with resistant hypertension and obstructive sleep apnoea

Letter

I thank Hynes and Mansfield for their review article addressing the diagnosis and management of obstructive sleep apnoea (OSA) in adults.¹

OSA is associated with increased risk of resistant hypertension (odds ratio 3.34) and adverse cardiovascular outcomes.² Higher urine and plasma aldosterone concentrations are associated with increased apnoea-hypopnoea index.³ In a recent study, 27% of individuals with OSA and resistant hypertension were shown to have primary aldosteronism.⁴ Treatment with continuous positive airway pressure alone is associated with modest reductions in 24-hour systolic (−5.92 mmHg) and diastolic (−4.44 mmHg) blood pressure in individuals with resistant hypertension and OSA.⁵

Studies of mineralocorticoid receptor antagonists have demonstrated significant effects on blood pressure and sleep apnoea symptoms in people with OSA associated with resistant hypertension.^6,7

A 3-month randomised open-label study (n=30 participants) evaluated spironolactone 20 to 40 mg daily in addition to existing antihypertensive therapy, compared with usual care, in patients with OSA and resistant hypertension.⁶ Significant reductions were demonstrated in the apnoea-hypopnoea index (−21.8 versus −1.8), hypopnoea index (−9.8 versus +2.7), oxygenation desaturation index (−20.8 versus −0.3) and plasma aldosterone concentration (−9.8 versus −2.9 ng/dL) in the spironolactone group compared with the control group. There was also a significant reduction in clinic blood pressure (−19.9/−5.7 mmHg versus −10.9/−2.4 mmHg) and 24-hour ambulatory blood pressure (−16.3/−14.9 mmHg versus −5.3/−2.9 mmHg) in the spironolactone group compared with the control group.⁶

A 3-month uncontrolled prospective observational trial of eplerenone 50 mg daily in 31 individuals with OSA and resistant hypertension (average 3.93 antihypertensive medications) demonstrated significant reduction in apnoea-hypopnoea index, blood pressure and arterial stiffness at 12 weeks.⁷

There are no published data regarding the use of finerenone in OSA and resistant hypertension to date.

Mineralocorticoid receptor antagonists may have specific benefits in the management of resistant hypertension and OSA. Monitoring of serum potassium is important in the setting of co-therapy with angiotensin converting enzyme inhibitors and angiotensin II receptor blockers because of the increased risk of hyperkalaemia.

Adam Morton
Senior Staff Specialist in Endocrinology and Obstetric Medicine, Mater Hospital, Brisbane

Conflicts of interest: none declared

 

References

1. Hynes D, Mansfield D. Diagnosis and management of obstructive sleep apnoea in adults. Aust Prescr 2024;47:52-6.
2. Ahmed AM, Nur SM, Xiaochen Y. Association between obstructive sleep apnea and resistant hypertension: systematic review and meta-analysis. Front Med 2023;10:1200952.
3. Ke X, Guo W, Peng H, Hu C, Zhang H, Peng C, et al. Association of aldosterone excess and apnea-hypopnea index in patients with resistant hypertension. Sci Rep 2017;7:45241.
4. Yan D, Zou X, Li X, Zeng Q, He H, Guo J, et al. Screening parameters for diagnosing primary aldosteronism in patients with moderate to severe obstructive sleep apnea hypopnea syndrome and resistant hypertension. Front Cardiovasc Med 2024;11:1383567.
5. Sun L, Chang YF, Wang YF, Xie QX, Ran XZ, Hu CY, et al. Effect of Continuous Positive Airway Pressure on Blood Pressure in Patients with Resistant Hypertension and Obstructive Sleep Apnea: An Updated Meta-analysis. Curr Hypertens Rep 2024;26:201-11.
6. Yang L, Zhang H, Cai M, Zou Y, Jiang X, Song L, et al. Effect of spironolactone on patients with resistant hypertension and obstructive sleep apnea. Clin Exp Hypertens 2016;38:464-8.
7. Krasińska B, Miazga A, Cofta S, Szczepaniak-Chichel L, Trafas T, Krasinski Z, et al. Effect of eplerenone on the severity of obstructive sleep apnea and arterial stiffness in patients with resistant arterial hypertension. Pol Arch Med Wewn 2016;126:330-9.

 

Authors’ response

Daniel Hynes and Darren Mansfield, the authors of the article, comment:

We thank Morton for their comments on our review. The bidirectional association between obstructive sleep apnoea (OSA) and hypertension is well described. Intermittent hypoxaemia from upper airway occlusion induces overactivation of the renin–angiotensin–aldosterone system. In turn, fluid and salt retention can increase rostral fluid shifts that may worsen underlying OSA severity.¹ Treatment of OSA has generally been shown to reduce aldosterone levels,² with blood pressure improvements as Morton highlighted. These links between resistant hypertension, aldosteronism and OSA highlight the importance of OSA screening in people with resistant hypertension.

Data supporting both a reduction of the apnoea-hypopnoea index and improved oxygen saturation using mineralocorticoid receptor antagonists in people with OSA and resistant hypertension are promising; however, this research remains limited to relatively small sample sizes. Yang’s study of spironolactone included 30 participants,³ and 31 were recruited in Krasińska’s study of eplerenone.⁴ Improvement in OSA symptoms has not been a commonly measured outcome in studies of mineralocorticoid receptor antagonists in people with OSA and resistant hypertension.

Alternative treatment options for OSA remain desirable, considering that long-term adherence with positive airway pressure is challenging for some individuals.⁵ We will await further research into the role of mineralocorticoid receptor antagonists, in the hope that these findings may be incorporated into future clinical practice.

 

References 2

1. Lombardi C, Pengo MF, Parati G. Systemic hypertension in obstructive sleep apnea. J Thorac Dis 2018;10:S4231-S43.
2. Wang Y, Li CX, Lin YN, Zhang LY, Li SQ, Zhang L, et al. The Role of Aldosterone in OSA and OSA-Related Hypertension. Front Endocrinol 2021;12:801689.
3. Yang L, Zhang H, Cai M, Zou Y, Jiang X, Song L, et al. Effect of spironolactone on patients with resistant hypertension and obstructive sleep apnea. Clin Exp Hypertens 2016;38:464-8.
4. Krasińska B, Miazga A, Cofta S, Szczepaniak-Chichel L, Trafas T, Krasinski Z, et al. Effect of eplerenone on the severity of obstructive sleep apnea and arterial stiffness in patients with resistant arterial hypertension. Pol Arch Med Wewn 2016;126:330-9.
5. Sawyer AM, Gooneratne NS, Marcus CL, Ofer D, Richards KC, Weaver TE. A systematic review of CPAP adherence across age groups: clinical and empiric insights for developing CPAP adherence interventions. Sleep Med Rev 2011;15:343-56.

 

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