What is the next step in managing a 66-year-old patient with essential hypertension (HTN) who remains hypertensive despite taking idapamide (diuretic) 2.5mg once daily and losartan (angiotensin II receptor blocker (ARB)) 25mg in the morning and 50mg in the evening?

Management of Uncontrolled Hypertension on Current Dual Therapy

Add a calcium channel blocker (amlodipine 5-10 mg once daily) as your next step, as this patient requires triple therapy with an ARB, thiazide-like diuretic, and calcium channel blocker to achieve blood pressure control. 1, 2

Current Medication Assessment

Your patient is on:

• Indapamide 2.5 mg once daily (thiazide-like diuretic) 3
• Losartan 75 mg total daily (25 mg morning + 50 mg evening = ARB) 4

Critical Issue with Current Regimen

• The losartan dosing is suboptimal and unconventional - the total daily dose of 75 mg is split unnecessarily, when losartan should be given as a single daily dose 4
• Before adding a third agent, optimize the losartan to 100 mg once daily (the maximum recommended dose for hypertension) 4
• The indapamide dose of 2.5 mg is appropriate and can be increased to 5 mg if needed, though adding another drug class is preferred over increasing to higher diuretic doses 3

Recommended Treatment Algorithm

Step 1: Optimize Current Medications

• Consolidate losartan to 100 mg once daily (taken in the morning) rather than the current split dosing of 75 mg total 4
• Continue indapamide 2.5 mg once daily 3
• Reassess blood pressure in 2-4 weeks 2

Step 2: Add Third Agent if BP Remains Elevated

• Add amlodipine 5 mg once daily (or another dihydropyridine calcium channel blocker) 1, 2
• This follows the International Society of Hypertension 2020 guidelines for non-Black patients: ARB → increase to full dose → add thiazide-like diuretic → add calcium channel blocker 1
• The combination of ARB + thiazide-like diuretic + calcium channel blocker is the standard triple therapy approach 1

Step 3: If Still Uncontrolled After Triple Therapy

• Add spironolactone 25 mg once daily as the fourth agent 1
• Alternative fourth-line agents if spironolactone is contraindicated or not tolerated: amiloride, doxazosin, eplerenone, clonidine, or beta-blocker 1

Target Blood Pressure

• Aim for BP <140/90 mmHg for this 66-year-old patient 1
• More aggressive targets of <130/80 mmHg may be considered based on cardiovascular risk, but the minimum acceptable target is <140/90 mmHg 1
• Achieve target within 3 months of treatment adjustments 1

Important Considerations Before Escalating Therapy

Check Medication Adherence

• Verify the patient is actually taking medications as prescribed - non-adherence is a common cause of apparent treatment resistance 2
• Consider once-daily dosing and single-pill combinations to improve adherence 1

Exclude Secondary Hypertension

• Evaluate for secondary causes if BP remains uncontrolled on triple therapy: 2
  • Primary aldosteronism (check aldosterone-to-renin ratio)
  • Renal artery stenosis
  • Obstructive sleep apnea
  • Pheochromocytoma

Reinforce Lifestyle Modifications

• Sodium restriction (<2 g/day) 2
• Weight loss if overweight 2
• Regular physical activity 2
• Limit alcohol consumption 2

Monitoring Parameters

• Recheck BP within 2-4 weeks after each medication adjustment 2
• Monitor serum potassium and creatinine when adding or increasing diuretics or ARBs 1
• Check for orthostatic hypotension, especially in this 66-year-old patient 5, 2

When to Refer to Specialist

• If BP remains uncontrolled despite optimized four-drug therapy (ARB + diuretic + calcium channel blocker + spironolactone/fourth agent) 2
• If secondary hypertension is suspected 2

Common Pitfalls to Avoid

• Don't increase indapamide beyond 2.5 mg without first optimizing losartan and adding a calcium channel blocker - doses of 5 mg indapamide provide minimal additional BP reduction but increase risk of hypokalemia 3, 6
• Don't use split dosing for losartan - it should be given once daily 4
• Don't add multiple medications simultaneously - titrate one agent at a time to assess response and tolerability 1