The Role of β-Blockers in the Evolving Treatment Landscape of Resistant Hypertension.

Resistant hypertension (RHTN) is estimated to affect approximately 15% of all patients with hypertension, although its reported prevalence varies according to the blood pressure (BP) thresholds used for diagnosis, the criteria applied to exclude secondary or pseudoresistant hypertension, and the characteristics of the study populations. Regardless of its current prevalence, RHTN is expected to be encountered with increasing frequency in routine clinical practice, driven by the rising prevalence of conditions that are directly or indirectly linked with its increased risk, such as obesity, diabetes mellitus, and chronic kidney disease (CKD). Consequently, recent clinical trials and hypertension guidelines have devoted substantial attention to RHTN, also considering its association with an increased risk of cardiovascular events and renal failure. In this narrative review, we summarize mechanistic insights and evidence from randomized clinical trials and real-world studies, as well as recommendations from current international guidelines, to provide an updated perspective on the management of RHTN. Among multiple systems, activation of the sympathetic nervous system (SNS) and the renin-angiotensin-aldosterone system represents a central pathophysiological mechanism in RHTN, promoting sodium retention and vascular dysfunction. β-blockers counteract SNS overactivity, a target mechanism not addressed by other first-line therapies, and have compelling indications in most comorbidities associated with RHTN, including coronary artery disease, heart failure, and atrial fibrillation. They can be used across diverse patient populations, including those with advanced CKD, and their side effects can be readily monitored and managed. Evidence from randomized trials and real-world studies supports their efficacy, tolerability, and safety even in high-risk populations. Emerging strategies, including a quadruple single-pill combination containing a β-blocker, may enhance adherence, optimize BP control, and simplify RHTN management.