What is the definition of Resistant (treatment-resistant) and Refractory (treatment-unresponsive) Hypertension (High Blood Pressure)?

From the Guidelines

Resistant hypertension is defined as blood pressure that remains above goal (typically >130/80 mmHg) despite concurrent use of three or more antihypertensive medications of different classes, one of which is a diuretic, at optimal doses, as stated in the 2024 ESC guidelines for the management of elevated blood pressure and hypertension 1. The definition of resistant hypertension is crucial in identifying patients who require more aggressive treatment and closer monitoring. According to the 2024 ESC guidelines, the recommended treatment of resistant hypertension includes reinforcement of lifestyle measures, addition of low-dose spironolactone to existing treatment, or the addition of further diuretic therapy if intolerant to spironolactone 1. Some key points to consider in the management of resistant hypertension include:

• Confirming medication adherence and ruling out white coat hypertension with ambulatory monitoring
• Considering secondary causes of hypertension, such as primary aldosteronism, renal artery stenosis, or obstructive sleep apnea
• Optimizing the existing regimen and adding a mineralocorticoid receptor antagonist like spironolactone (25-50 mg daily)
• Considering other agents like beta-blockers, alpha-blockers, or centrally-acting agents
• Refractory hypertension may require specialized interventions such as device-based therapies or clinical trial enrollment, as noted in the 2024 ESC guidelines 1. It is essential to note that the pathophysiology of resistant hypertension often involves volume overload and increased sympathetic nervous system activity, while refractory hypertension appears more strongly linked to sympathetic overdrive rather than volume issues. The 2024 ESC guidelines provide the most recent and highest quality evidence for the management of resistant hypertension, and therefore, its recommendations should be prioritized in clinical practice 1.

From the Research

Definition of Resistant and Refractory Hypertension

• Resistant hypertension (RHT) is defined as blood pressure that remains above guideline-directed targets despite the use of three anti-hypertensives, usually including a diuretic, at optimal or maximally tolerated doses 2, 3, 4, 5, 6.
• Refractory hypertension is defined as uncontrolled blood pressure despite the use of ≥5 antihypertensive agents of different classes, including a long-acting thiazide-like diuretic and an MR (mineralocorticoid receptor) antagonist, at maximal or maximally tolerated doses 3, 5.

Key Considerations

• Pseudoresistance and secondary hypertension must be excluded to make the diagnosis of resistant hypertension 2, 3, 6.
• Non-pharmacologic management should be optimized prior to consideration of fourth-line anti-hypertensive agents or advanced interventions 2.
• Risk factors for the development of resistant hypertension include diabetes, obesity, and other adverse lifestyle factors 2.
• Resistant hypertension is associated with increased cardiovascular morbidity and mortality 2, 3, 4, 5.

Diagnostic Criteria

• Blood pressure should be measured accurately, and out-of-office BP measurement should be used to confirm inadequate BP control 3.
• The diagnosis of resistant hypertension should be made after excluding non-adherence to medication and other causes of pseudo-resistant hypertension 4, 5, 6.