From the Guidelines
Resistant hypertension should be managed by reinforcing lifestyle measures, especially sodium restriction, and adding low-dose spironolactone to existing treatment, as recommended by the 2024 ESC guidelines for the management of elevated blood pressure and hypertension 1. The causes of resistant hypertension are multifactorial, including nonadherence to medication, white coat hypertension, and secondary causes such as obstructive sleep apnea, primary aldosteronism, renal artery stenosis, and chronic kidney disease. Key management strategies include:
- Optimizing the current regimen with a thiazide diuretic, an ACE inhibitor or ARB, and a calcium channel blocker
- Adding spironolactone or eplerenone as a fourth agent if blood pressure remains uncontrolled
- Considering beta-blockers, alpha-blockers, or centrally acting agents for patients who remain hypertensive
- Investigating secondary causes of hypertension and addressing contributing lifestyle factors
- Referring patients to a hypertension specialist if blood pressure remains uncontrolled despite optimal treatment. Lifestyle modifications, such as sodium restriction, weight loss, regular physical activity, limited alcohol consumption, and the DASH diet, are also crucial in managing resistant hypertension, as they target different physiological mechanisms of blood pressure regulation, including volume control, sympathetic nervous system activity, and the renin-angiotensin-aldosterone system 1. In patients with resistant hypertension, catheter-based renal denervation may be considered as an additional treatment option if performed at a medium-to-high volume center, and after a shared risk-benefit discussion and multidisciplinary assessment 1. Overall, a comprehensive approach that incorporates lifestyle modifications, optimal medication management, and investigation of secondary causes is essential for effectively managing resistant hypertension and improving patient outcomes.
From the Research
Definition and Diagnosis of Resistant and Refractory Hypertension
- Resistant hypertension is defined as blood pressure levels remaining elevated above target despite changes in lifestyle and concurrent use of at least three antihypertensive agents, including a long-acting calcium channel blocker, a blocker of the renin-angiotensin system, and a diuretic 2, 3.
- 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 a mineralocorticoid receptor antagonist, at maximal or maximally tolerated doses 3, 4.
- Diagnosis of resistant hypertension requires confirmation of blood pressure levels above target by out-of-office blood pressure measurements and exclusion of secondary causes of hypertension 2.
Causes of Resistant and Refractory Hypertension
- Fluid retention, mediated largely by aldosterone excess, is the predominant mechanism underlying resistant hypertension 3.
- Patients with refractory hypertension typically exhibit increased sympathetic nervous system activity 3.
- Secondary causes of hypertension, including obstructive sleep apnea, primary aldosteronism, and renovascular disease, are common in patients with resistant hypertension and often coexist in the same patient 5.
Management of Resistant and Refractory Hypertension
- Lifestyle changes, such as reduced sodium and alcohol intake, regular physical activity, weight loss, and discontinuation of substances that can interfere with blood pressure control, are recommended 2.
- Pharmacological treatment should be tailored to each patient's specific phenotype, and current treatment should be rationalized, including single pill combination treatment where antihypertensive drugs should be provided at the maximum tolerated dose 2, 6.
- The fourth line of treatment for patients with resistant hypertension should include mineralocorticoid receptor antagonists, such as spironolactone, as demonstrated in the PATHWAY-2 trial and meta-analyses 2.
- Alternatives to spironolactone include amiloride, doxazosin, eplerenone, clonidine, and beta-blockers, as well as any other antihypertensive drugs not already in use 2.
- Novel interventional therapies, including baroreflex activation and renal denervation, have shown promise in lowering blood pressure safely in patients with resistant hypertension 5, 4.