Can I get refills for propranolol extended‑release 120 mg, valsartan‑hydrochlorothiazide 320/25 mg, and nifedipine extended‑release 60 mg despite having resistant hypertension with systolic 170‑190 mm Hg and diastolic 80‑95 mm Hg?

Do Not Refill These Medications Without Urgent Intervention

You should NOT simply refill these medications as currently prescribed, because this patient has uncontrolled resistant hypertension (systolic 170-190 mmHg) despite being on three antihypertensive agents, which places them at 2- to 6-fold higher risk of myocardial infarction, stroke, end-stage renal disease, and death. 1, 2 The current regimen requires immediate optimization before any refills are issued.

Immediate Actions Required Before Refilling

Confirm True Resistant Hypertension

• Perform ambulatory blood pressure monitoring (ABPM) or home blood pressure monitoring to exclude white-coat hypertension, which accounts for approximately 50% of apparent resistant hypertension cases. 1, 2, 3
• Verify medication adherence through direct questioning, pill counts, or pharmacy records—nonadherence is responsible for roughly half of treatment resistance. 2, 3
• Ensure proper BP measurement technique using an appropriately sized cuff for the patient's arm circumference, as improper technique leads to falsely elevated readings. 2, 3

Optimize the Current Three-Drug Regimen FIRST

• Replace valsartan-hydrochlorothiazide 320/25 mg with valsartan-chlorthalidone 320/12.5-25 mg (or add chlorthalidone 12.5-25 mg separately if the combination is unavailable), because thiazide-like diuretics (chlorthalidone, indapamide) are significantly more effective than hydrochlorothiazide for resistant hypertension. 1, 2, 3 This is the single most important medication change.
• Verify that all three agents are at maximal tolerated doses before adding a fourth drug—inadequate dosing is a common cause of treatment failure. 2, 3
• Intensify lifestyle modifications: sodium restriction to <2400 mg/day, weight loss if overweight, limit alcohol to ≤2 drinks/day for men or ≤1 drink/day for women, and implement regular aerobic exercise. 2, 3

Screen for Secondary Causes and Interfering Substances

• Screen for primary aldosteronism by checking morning plasma aldosterone-to-renin ratio, even if serum potassium is normal. 1, 2, 3
• Screen for obstructive sleep apnea using validated questionnaires and refer for sleep study if indicated. 2, 3
• Check baseline eGFR, serum potassium, and TSH to assess for chronic kidney disease and thyroid dysfunction. 2
• Discontinue or minimize interfering substances: NSAIDs, stimulants, oral contraceptives, certain antidepressants, and excessive alcohol intake. 2

Adding a Fourth-Line Agent

Spironolactone as First Choice

• Add spironolactone 25 mg once daily as the fourth-line agent, provided serum potassium is <4.5 mEq/L and eGFR is >45 mL/min/1.73m². 1, 2, 3 This was the most effective fourth-line option in the PATHWAY-2 randomized controlled trial.
• Increase to 50 mg daily if BP remains uncontrolled after 4 weeks and the medication is well-tolerated. 2
• Monitor serum potassium and creatinine within 1-2 weeks after initiation, especially since the patient is on valsartan (a RAS blocker). 2, 3

Alternative Fourth-Line Agents (If Spironolactone Contraindicated)

• Eplerenone 50-200 mg daily (potentially divided twice daily) if the patient cannot reliably monitor potassium levels or develops gynecomastia on spironolactone. 2
• Doxazosin (alpha-blocker) may be used when mineralocorticoid receptor antagonists are contraindicated due to hyperkalemia or reduced renal function. 2
• Vasodilating beta-blockers (labetalol, carvedilol, or nebivolol) represent the safest fourth-line option for patients who cannot undergo regular laboratory monitoring, as they do not require potassium checks—but they are less potent than spironolactone. 2

Target Blood Pressure and Monitoring

• Target BP <130/80 mmHg per ACC/AHA guidelines. 1, 2, 3
• Reassess BP response within 2-4 weeks of any medication adjustment. 2
• Use home BP monitoring to guide medication titration and improve adherence. 2, 3

When to Refer to a Specialist

• Refer to a hypertension specialist if BP remains uncontrolled (>130/80 mmHg) after optimizing the four-drug regimen with lifestyle modifications, or if complications arise such as severe hyperkalemia, progressive renal dysfunction, or difficulty managing the regimen. 1, 2, 3

Common Pitfalls to Avoid

• Do not continue hydrochlorothiazide—switching to chlorthalidone or indapamide provides superior efficacy and is the most critical optimization step. 1, 2, 3
• Do not add a fourth agent before maximizing doses of the first three agents and switching to a thiazide-like diuretic. 2, 3
• Do not use beta-blockers as first, second, or third-line agents in uncomplicated resistant hypertension—they are explicitly fourth-line only. 2
• Never abruptly discontinue propranolol—taper to avoid rebound hypertension or exacerbation of angina. 2