Resistant hypertension and renal denervation — viva

Stem

Practice viva. The examiner describes a patient whose office BP stays high on three drugs and works through definition and confirmation, secondary causes, the fourth drug and its alternatives, and renal denervation.^[1][2]

Branch A — Is it really resistant?

Examiner: How do ESC 2024 and AHA/ACC 2025 define resistant hypertension?^[1][2]

Strong answer:

• ESC 2024: hypertension is resistant when appropriate lifestyle measures and maximum or maximally tolerated doses of a thiazide or thiazide-like diuretic, a RAS blocker and a CCB fail to lower office systolic and diastolic BP to <140 mmHg and/or <90 mmHg, respectively, confirmed by HBPM or ABPM.^[1]
• AHA/ACC 2025: BP above goal despite 3 antihypertensive medications with complementary mechanisms, including a diuretic, at maximally tolerated doses, or BP at goal but requiring ≥4 medications.^[2]
• ESC 2024 does not use "controlled resistant hypertension" or "refractory hypertension", and with eGFR <30 mL/min/1.73 m² it requires an adequately up-titrated loop diuretic to define resistant hypertension.^[1]

Follow-up: What must you exclude first, and how?^[1]

• Pseudo-resistance, including non-adherence (ESC 2024); its Table 11 causes are poor adherence and persistence, white-coat phenomenon, poor BP measurement method, Osler phenomenon, clinician inertia and, rarely, Munchausen syndrome.^[1]
• Out-of-office BP: AHA/ACC 2025 says it is reasonable to exclude white-coat effect with out-of-office BP monitoring in apparent treatment-resistant hypertension (COR 2a, LOE C-LD) and prefers HBPM for this in people taking antihypertensive medication.^[2]
• Adherence: ESC 2024 says objective evaluation (directly observed treatment or detecting prescribed drugs in blood or urine) should be considered if resources allow (Class IIa, Level B), and that most apparent treatment-resistant hypertension is accounted for by non-adherence.^[1]

Branch B — Secondary causes

Examiner: Which secondary causes do you look for, and how?^[2]

Strong answer:

• AHA/ACC 2025 says secondary hypertension is more common in resistant hypertension, particularly primary aldosteronism, OSA, renal parenchymal disease and renovascular disease, and a detailed evaluation including medication review is beneficial (COR 1, LOE B-NR).^[2]
• Primary aldosteronism: AHA/ACC 2025 recommends screening in resistant hypertension regardless of hypokalaemia (COR 1, LOE B-NR) with plasma aldosterone, renin activity and their ratio (COR 1, LOE C-LD), continuing most drugs other than MRAs (COR 1, LOE C-EO).^[2]
• ESC 2024 Table 13 (optional tests to screen for secondary hypertension in the presence of suggestive signs, symptoms or medical history) includes: aldosterone-to-renin ratio for primary aldosteronism; renal Doppler ultrasound or abdominal CT angiogram or MRI for renovascular hypertension; 24 h urinary and/or plasma metanephrine and normetanephrine for phaeochromocytoma/paraganglioma; overnight ambulatory polysomnography for obstructive sleep apnoea syndrome; and plasma creatinine, sodium and potassium, eGFR, urine dipstick for blood and protein, urinary albumin-to-creatinine ratio and renal ultrasound for renal parenchymal disease.^[1]
• ESC 2024 says sleep apnoea should be suspected in all patients with resistant hypertension.^[1]

Follow-up: He is on a beta-blocker. Does that matter for the ratio?^[1]

• ESC 2024 Table 12 lists beta-adrenergic blockers as raising the ARR, a false-positive effect; ESC 2024 allows testing on current drugs with interpretation in their context, or stopping interfering drugs whenever feasible for a clean screen.^[1]

Branch C — The fourth drug

Examiner: Resistance is confirmed and no secondary cause found. What next?^[1][2]

Strong answer:

• ESC 2024: in resistant hypertension with BP uncontrolled despite first-line BP-lowering therapies, adding spironolactone to existing treatment should be considered (Class IIa, Level B), at 25–50 mg daily, restricted to eGFR ≥30 mL/min/1.73 m² and potassium ≤4.5 mmol/L, with electrolytes and kidney function monitored soon after initiation and frequently thereafter.^[1]
• AHA/ACC 2025: in uncontrolled resistant hypertension despite optimal first-line therapy (ACEi or ARB plus CCB and thiazide-like diuretic [chlorthalidone or indapamide]) and with an eGFR of ≥45 mL/min/1.73 m², adding an MRA is recommended to control BP (COR 1, LOE B-R).^[2]
• AHA/ACC 2025 reports that RCTs in patients with resistant hypertension and an eGFR of ≥45 mL/min/1.73 m² showed that adding spironolactone 25-50 mg/day as the fourth drug reduced home and 24-hour SBP by 6.6 to 8.7 mm Hg compared with placebo; the reduction was greater than with added doxazosin or bisoprolol.^[2]

Follow-up: And if spironolactone is not tolerated?^[1]

• ESC 2024: when spironolactone is not effective or tolerated, eplerenone instead, or a beta-blocker if not already indicated and, next, a centrally acting drug, an alpha-blocker, hydralazine or a potassium-sparing diuretic should be considered (Class IIa, Level B); if eplerenone is used, higher doses (50–200 mg daily) and twice-daily dosing may be necessary to achieve a BP-lowering effect.^[1]
• AHA/ACC 2025: in uncontrolled resistant hypertension when an MRA cannot be tolerated or is contraindicated, adding amiloride, a beta-blocker, an alpha-blocker, a central sympatholytic, a dual endothelin receptor antagonist or a direct vasodilator is reasonable to control BP (COR 2a, LOE B-NR); direct vasodilators should be combined with a beta-blocker and a loop diuretic.^[2]

Branch D — Renal denervation

Examiner: Where does renal denervation fit?^[1][2]

Strong answer:

• ESC 2024: to reduce BP, and if performed at a medium-to-high volume centre, it may be considered for resistant hypertension uncontrolled on three drugs including a thiazide or thiazide-like diuretic, when the patient expresses a preference after shared risk-benefit discussion and multidisciplinary assessment (Class IIb, Level B); it is not recommended as a first-line BP-lowering intervention for hypertension (Class III, Level C), and it is not recommended in patients with moderate-to-severely impaired renal function (eGFR <40 mL/min/1.73 m²) or secondary causes of hypertension, until further evidence becomes available (Class III, Level C).^[1]
• AHA/ACC 2025: it may be reasonable as an adjunct in carefully selected patients with office SBP 140-180 mm Hg and DBP ≥90 mm Hg and eGFR ≥40 mL/min/1.73 m² who are resistant despite optimal treatment or intolerant of additional drugs (COR 2b, LOE B-R), after multidisciplinary team evaluation (COR 1, LOE B-NR) and shared decision-making (COR 1, LOE C-EO).^[2]
• ESC 2024 reports that, for current RDN catheter technologies, meta-analyses show placebo-corrected systolic BP lowering of approximately 6 mmHg on office BP and 4 mmHg on 24 h ABPM; the average BP-lowering effect appears no more than for one standard BP-lowering medication.^[1]

Follow-up: Why not Class I?^[1]

• ESC 2024 says that, without outcomes trials, RDN cannot reach its Class I threshold; there are no adequately powered outcomes trials showing that it reduces CVD events and is safe long term.^[1]
• AHA/ACC 2025 says RDN should not be considered curative or a full replacement for antihypertensive drugs.^[2]