Resistant hypertension in a woman with type 2 diabetes — case discussion

Presentation

Practice case (not a real patient). A 59-year-old woman is referred by her general practitioner in Australia because her automated office BP (AOBP) stays at 156/94 mmHg despite irbesartan, amlodipine and hydrochlorothiazide, each at the maximum dose she tolerates.^[4][1] She has type 2 diabetes. Her eGFR is 64 mL/min/1.73 m² and her potassium 3.9 mmol/L.^[1][2]

Step 1 — Is this resistant hypertension yet?

Discussion:

• Not yet. ESC 2024 requires the uncontrolled office values to be confirmed by out-of-office BP measurement (HBPM or ABPM), and pseudo-resistance, including non-adherence, must be excluded.^[1]
• The Australian position statement makes AOBP the recommended measurement standard, with an AOBP hypertension threshold of 135/85 mmHg; the NHFA 2016 summary says ambulatory and/or home BP monitoring should be offered if clinic BP is ≥140/90 mmHg.^[4][3]
• Her home BP averages 149/91 mmHg, above the ESC 2024 Table 5 home threshold of ≥135/85 mmHg.^[1]
• Detection of her prescribed drugs in urine confirms she takes them; ESC 2024 says objective adherence evaluation should be considered in apparent resistant hypertension if resources allow (Class IIa, Level B).^[1]

Step 2 — Optimise the first three drugs

• ESC 2024 says BP control may be improved by switching hydrochlorothiazide to a long-acting thiazide-like diuretic such as chlorthalidone, and recommends single-pill combinations in resistant hypertension to reduce pill burden.^[1]
• Hydrochlorothiazide is replaced with chlorthalidone at the maximum dose she tolerates; her home BP stays at 147/90 mmHg.^[1]

Step 3 — Look for a cause

• AHA/ACC 2025 recommends screening for primary aldosteronism in resistant hypertension regardless of whether hypokalaemia is present (COR 1, LOE B-NR), and continuing most antihypertensive drugs other than MRAs before initial screening (COR 1, LOE C-EO).^[2]
• Her aldosterone-to-renin ratio, drawn on irbesartan, amlodipine and chlorthalidone, is negative; ESC 2024 says a ratio taken on current drugs needs to be interpreted in the context of the specific medications the patient is taking.^[1]
• ESC 2024 Table 12 lists ARBs as lowering the ratio (false negative), and AHA/ACC 2025 says thiazide-type diuretics, its term for hydrochlorothiazide, chlorthalidone and indapamide, can stimulate both renin and aldosterone.^[1][2]
• AHA/ACC 2025 says that if screening results are negative or borderline in a patient with a high level of suspicion for primary aldosteronism, and confirmation will change management, potentially interfering drugs may be temporarily replaced with noninterfering ones (nondihydropyridine CCBs, vasodilators, peripheral alpha-blockers and potentially dihydropyridine CCBs) for at least 2 to 4 weeks before repeat testing; ESC 2024 says long-acting CCBs and alpha-receptor antagonists do not interfere with the ARR.^[2][1]
• Her clinicians judge suspicion to be high and a diagnosis would change her treatment, so irbesartan and chlorthalidone are replaced with a peripheral alpha-blocker for 4 weeks while amlodipine continues; the repeat ratio is again negative, and she goes back to irbesartan and chlorthalidone.^[2][1]
• She has no symptoms of sleep apnoea, but ESC 2024 says it should be suspected in all patients with resistant hypertension and lack of symptoms does not rule it out, so overnight polysomnography is arranged and is normal.^[1]
• ESC 2024 Table 13 renal screening (creatinine, electrolytes, eGFR, urine dipstick, albumin-to-creatinine ratio, renal ultrasound) and renal Doppler ultrasound are unremarkable.^[1]
• ESC 2024 says patients with resistant hypertension should be considered for referral to clinical centres with expertise in hypertension management for further testing (Class IIa, Level B), and she is seen in a hypertension clinic.^[1]

Step 4 — The fourth drug

• ESC 2024: in resistant hypertension uncontrolled despite first-line therapies, adding spironolactone should be considered (Class IIa, Level B); she meets the eGFR ≥30 mL/min/1.73 m² and potassium ≤4.5 mmol/L limits.^[1]
• AHA/ACC 2025: in adults with uncontrolled resistant hypertension despite optimal first-line therapy (ACEi or ARB plus CCB and thiazide-like diuretic [chlorthalidone or indapamide]) and an eGFR of ≥45 mL/min/1.73 m², addition of an MRA is recommended to control BP (COR 1, LOE B-R).^[2]
• ESC 2024 reports that in resistant hypertension with type 2 diabetes, spironolactone (25–50 mg daily) reduced BP and albuminuria.^[1]
• Spironolactone 25 mg daily is started, with electrolytes and kidney function checked soon after initiation and frequently thereafter (ESC 2024).^[1]

Step 5 — She asks about renal denervation

• Four weeks after starting spironolactone her home BP averages 128/78 mmHg, below the ESC 2024 home threshold of ≥135/85 mmHg, so the ESC 2024 RDN row for resistant hypertension uncontrolled despite a three-drug combination does not apply to her.^[1]
• AHA/ACC 2025 says RDN should not be considered a curative therapy or a full replacement for antihypertensive drugs, and ESC 2024 says many adults undergoing RDN will likely need ongoing BP-lowering drugs.^[2][1]

Learning points

• Confirm resistance out of office and exclude pseudo-resistance, including non-adherence, before calling it resistant (ESC 2024).^[1]
• Screen for primary aldosteronism in resistant hypertension regardless of potassium (AHA/ACC 2025, COR 1, LOE B-NR), and suspect sleep apnoea in all patients with resistant hypertension (ESC 2024).^[2][1]
• ESC 2024: in resistant hypertension with BP uncontrolled despite first-line BP-lowering therapies, adding spironolactone should be considered (Class IIa, Level B), restricted to an eGFR of ≥30 mL/min/1.73 m² and potassium ≤4.5 mmol/L. AHA/ACC 2025: in uncontrolled resistant hypertension despite optimal ACEi or ARB, CCB and thiazide-like diuretic, with an eGFR of ≥45 mL/min/1.73 m², adding an MRA is recommended to control BP (COR 1, LOE B-R).^[1][2]
• In Australia, AOBP is the recommended measurement standard, with a hypertension threshold of 135/85 mmHg.^[4]