Paulina Połetek

Arterial hypertension remains one of the leading modifiable risk factors for cardiovascular and renal morbidity and mortality worldwide, while resistant hypertension continues to represent a major therapeutic challenge despite the widespread use of conventional antihypertensive agents. Recent advances in the understanding of hypertension pathophysiology have enabled the development of novel pharmacological strategies targeting previously unexplored mechanisms. This review summarizes recently approved and emerging drugs for hypertension, with particular emphasis on agents acting on the renin–angiotensin–aldosterone system (RAAS), endothelin pathway, aldosterone synthesis, and RNA interference technology. Novel approaches include modulation of the ACE2/angiotensin-(1–7)/Mas receptor axis, inhibition of aminopeptidase A, and targeting tissue-specific RAAS activity, aiming to counteract the deleterious effects of classical RAAS activation. Dual endothelin receptor antagonists, particularly aprocitentan, have demonstrated significant and sustained blood pressure reduction in resistant hypertension with improved tolerability compared with earlier endothelin receptor antagonists. Highly selective aldosterone synthase inhibitors, including baxdrostat, lorundrostat, vicadrostat, and dexfadrostat, provide effective blood pressure lowering while minimizing cortisol suppression associated with previous agents, although hyperkalemia remains an important adverse effect. Small interfering RNA (siRNA)-based therapies represent an innovative therapeutic class, with zilebesiran producing prolonged suppression of angiotensinogen synthesis and sustained antihypertensive effects after infrequent subcutaneous administration. Collectively, these therapies offer promising alternatives for patients with uncontrolled or resistant hypertension and may provide additional cardiovascular and renal protection beyond blood pressure reduction. Nevertheless, many of these agents remain under clinical investigation, and further large-scale, long-term studies are required to establish their safety, cost-effectiveness, and impact on cardiovascular outcomes before their routine incorporation into clinical practice.

The aging of the population and the increasing prevalence of multimorbidity contribute to the widespread use of polypharmacotherapy, which in turn elevates the risk of adverse drug reactions and clinically significant drug–drug interactions. One of the key yet frequently underestimated issues in clinical practice is the prescribing cascade, which occurs when an adverse drug reaction is misinterpreted as a new medical condition, leading to the initiation of an additional medication. This phenomenon is particularly relevant in the elderly population, in whom altered pharmacokinetics and pharmacodynamics, together with reduced organ reserve, increase susceptibility to adverse drug events, including nephrotoxicity. The objective of this paper is to review current evidence on the mechanisms and clinical consequences of the prescribing cascade-with particular emphasis on renal function deterioration—as well as strategies for its prevention in the geriatric population. Analysis of the literature indicates that prescribing cascades remain insufficiently recognized in clinical practice, despite the availability of pharmacotherapy assessment tools such as the Beers Criteria and the STOPP/START criteria. Documented prescribing cascades have been shown to contribute to deterioration in health status and quality of life, an increased frequency of hospitalizations, and a greater burden on healthcare systems. Particularly concerning are cascades involving cardiovascular, neurological, and analgesic medications, which may induce or exacerbate renal injury, ultimately leading to chronic kidney disease and organ failure. Prescribing cascades represent a significant yet frequently underestimated threat to the efficacy and safety of pharmacotherapy in older adults. Their consequences may extend beyond reduced quality of life and increased treatment costs to include serious complications such as the development of renal failure. Enhancing clinicians’ awareness, conducting systematic medication reviews, and employing validated assessment tools are essential for the identification and prevention of prescribing cascades, thereby reducing the risk of renal injury and improving clinical outcomes.