RESISTANT HYPERTENSION: EFFICACY OF SPIRONOLACTONE AND EMERGING PHARMACOLOGICAL THERAPIES IN CURRENT MANAGEMENT

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Abstract
Resistant hypertension (RH) is a multifactorial condition associated with high cardiovascular morbidity and mortality and remains a major therapeutic challenge. This study aimed to critically review the available scientific evidence on the efficacy of spironolactone and the role of emerging pharmacological therapies in the management of RH. An integrative literature review was conducted, including publications indexed in PubMed, Scopus, Web of Science, SciELO, and the Cochrane Library between 2015 and 2025. Randomized clinical trials, systematic reviews, meta-analyses, and clinical guidelines evaluating pharmacological interventions for RH were included. The final sample comprised 27 high-quality studies. The findings demonstrated that spironolactone remains the most effective fourth-line drug, achieving an average systolic blood pressure reduction of 8 to 13 mmHg and significant improvement in resistant blood pressure control. Nonsteroidal mineralocorticoid receptor antagonists, such as finerenone and eplerenone, showed comparable efficacy with fewer adverse effects. Moreover, emerging therapies—including SGLT2 inhibitors, angiotensin receptor–neprilysin inhibitors (ARNIs), and renal denervation—showed complementary potential in blood pressure control and cardiovascular protection. It is concluded that spironolactone remains the gold-standard pharmacological treatment for RH, while novel therapies broaden the possibilities for personalized and integrated management, reinforcing the importance of multidisciplinary approaches and long-term comparative studies.