Approaches in the Treatment of Uncontrolled Hypertension

Despite the availability of antihypertensive drugs, many patients worldwide have uncontrolled hypertension (1,2). In this regard, the term „resistant hypertension“ was introduced, with a prevalence of 10%-20% in hypertensive patients (3). According to the current guidelines of the European Association of Cardiology, hypertension is defined as resistant when the treatment strategy, which includes appropriate lifestyle measures and treatment with maximum or maximally tolerated doses of diuretics (thiazides and thiazide-like diuretics), blockers of the renin-angiotension-aldosterone system (RAAS) and calcium channel blockers, fails to lower systolic arterial pressure <140 mm Hg and/or diastolic arterial pressure <90 mm Hg (4). Compared to patients who achieve adequate blood pressure control with antihypertensives, patients with resistant hypertension have a worse prognosis and consequently a higher risk of myocardial infarction, stroke and end-stage renal disease, with two to six times higher mortality (5,6). The cause of uncontrolled hypertension is usually identified in secondary hypertension), with a prevalence of up to 30% among patients with resistant hypertension (7,8). In addition to secondary hypertension, it is important to rule out pseudoresistant hypertension, including that caused by non-adherence to treatment (4). In this regard, large observational studies have found that within one year, approximately 50% of patients stop taking antihypertensive medications for various reasons, such as inadequacy, adverse drug reactions, and socioeconomic variables (9). Uncontrolled hypertension is significantly associated with increased sympathetic activity, which can be caused by afferent signals originating from the kidneys and the influence of sympathetic tone by stimulating hypothalamic centers (10). Chronic activation of renal sympathetic nerves is key in the pathogenesis of hypertension through various mechanisms (reabsorption of salt and water in renal tubules, reduction of renal perfusion and consequently glomerular filtration rate, activation of the RAAS cascade) (9). Consequently, renal denervation (RDN) has emerged as a therapeutic option in conditions of overactive central sympathetic nervous system (10). This chapter explores the role of SGLT2i in the treatment of hypertension, with a focus on their mechanisms of action, recent clinical evidence, and future implications. The introduction of this drug class may represent a paradigm shift in the management of UAH, offering new opportunities for more effective and individualized therapeutic strategies.