Resistant hypertension: Epidemiology, mechanisms and contemporary therapeutic strategies

Resistant hypertension (RH), defined as uncontrolled blood pressure on three or more antihypertensive agents (including a diuretic) or controlled blood pressure on four or more, poses a major clinical challenge. It disproportionately drives adverse cardiovascular outcomes, including stroke, heart failure and chronic kidney disease. Accurate diagnosis first requires distinguishing true RH from pseudo-resistance, which stems from inaccurate measurement, poor medication adherence and clinical inertia. The pathophysiology is multifactorial, driven by mechanisms such as sympathetic nervous system overactivity, renin-angiotensin-aldosterone system dysregulation, obesity and obstructive sleep apnoea. Consequently, effective management extends beyond mere drug intensification. It demands a comprehensive strategy that addresses lifestyle factors, ensures therapeutic adherence and treats secondary causes. For eligible patients, device-based therapies, such as renal denervation, are emerging as valuable adjuncts to pharmacological treatment. This article synthesizes the current understanding of RH's epidemiology, pathophysiology and diagnostic workup. It also critically examines the evolving landscape of integrated therapeutic strategies, discussing on-going controversies and future research directions to improve patient outcomes.