Efficacy of Spironolactone Combined With Antihypertensive Drugs in Patients With Primary Aldosteronism

Primary aldosteronism (PA) is one of the most common causes of endocrine and treatment-resistant hypertension. Current guidelines suggest that surgery and aldosterone receptor antagonists (MRAs), such as spironolactone, are the main treatment for PA. Patients with aldosterone-producing adenoma who decline surgery, as well as those with idiopathic hyperaldosteronism, are usually treated with spironolactone. However, there is a lack of large-scale, long-term, prospective, randomized controlled trials on spironolactone. In a retrospective cohort of 602 PA patients treated with long-term spironolactone therapy, Hundemer et al. found that the 10-year risk of major cardiovascular events and all-cause mortality was increased, compared with that in patients with essential hypertension. In contrast, PA patients who underwent adrenalectomy had a lower risk of cardiorenal vascular events than that in the spironolactone-treated patients, which was comparable to that of patients with essential hypertension. Further analysis revealed that if PA patients remained in a low-renin state after drug therapy, their risk of myocardial infarction, stroke, and heart-failure hospitalization was almost three-fold higher than that in patients with essential hypertension. Therefore, high doses of spironolactone (60\~100 mg/d) were recommended to relieve renin suppression. However, prolonged high-dose spironolactone is associated with numerous side effects, including hyperkalaemia, gynaecomastia and sexual dysfunction in men, menstrual irregularities in women, and central-nervous-system symptoms. Moreover, MRAs only block the effect of aldosterone at the receptor level, failing to suppress aldosterone synthesis. In addition, aldosterone exhibits receptor-independent actions. Consequently, whether spironolactone mitigates aldosterone-mediated cardiovascular and cerebrovascular events remains uncertain, and the optimal dose with fewer adverse effects needs to be defined. To clarify the optimal dose of spironolactone treatment and the long-term outcomes on cardiovascular and cerebrovascular events, the researchers conducted a long-term study involving patients with lateralized PA who are unwilling to undergo surgery. When the blood pressure fails to meet the criteria, antihypertensive drugs such as amlodipine and irbesartan, are combined. the PA patients will be confirmed as unilateral PA based on the results of adrenal venous sampling and different doses of spironolactone. The PA patients will take spironolactone treatment as part of their regular medical care for more than 12 months. The blood pressures, biochemical remission, cardiovascular and renal damage, and cardiovascular and cerebrovascular events will be analyzed after the spironolactone treatment. The antihypertensive efficacy and adverse reactions will be studied.