In a 62‑year‑old woman with hypertension whose systolic blood pressure remains 140–150 mm Hg despite losartan 50 mg daily, what medication should be added?

Management of Uncontrolled Hypertension on Losartan 50 mg

Add a thiazide or thiazide-like diuretic (hydrochlorothiazide 12.5–25 mg once daily, chlorthalidone 12.5–25 mg once daily, or indapamide 2.5 mg once daily) to the current losartan 50 mg regimen. 1

Rationale for Adding a Diuretic First

Before adding a second agent, verify that the patient is taking losartan consistently, as non-adherence is a common cause of apparent treatment failure. 1 However, in this case with persistent systolic pressures in the 140s–150s, combination therapy is clearly indicated.

The combination of an ARB (losartan) with a thiazide diuretic provides additive blood pressure-lowering effects and is a guideline-endorsed first-line combination strategy. 1 This approach is superior to simply increasing losartan to 100 mg as monotherapy, because combination therapy from different drug classes yields better blood pressure control than dose escalation of a single agent. 2

Specific Diuretic Options

Choose one of the following thiazide or thiazide-like diuretics:

• Hydrochlorothiazide 12.5–25 mg once daily (most commonly used, widely available as fixed-dose combination with losartan) 1, 3
• Chlorthalidone 12.5–25 mg once daily (longer half-life, may provide more consistent 24-hour control) 2
• Indapamide 2.5 mg once daily (thiazide-like diuretic with favorable metabolic profile) 4

Fixed-dose single-pill combinations (losartan/hydrochlorothiazide) are strongly preferred because they markedly improve medication adherence and persistence. 2

Target Blood Pressure and Monitoring

• Aim for blood pressure <130/80 mm Hg to reduce cardiovascular risk in this 62-year-old woman. 1, 2
• Re-evaluate blood pressure every 2–4 weeks after adding the diuretic, with the goal of reaching target within 3 months. 2
• Monitor serum potassium and creatinine within 1–2 weeks after adding the diuretic, especially given the patient's age and concurrent ARB therapy. 1, 2

Escalation Strategy if Dual Therapy Fails

If blood pressure remains ≥140/90 mm Hg after 4–8 weeks on losartan plus a thiazide diuretic at optimal doses:

• Add a dihydropyridine calcium channel blocker (amlodipine 5–10 mg once daily) to create triple therapy: ARB + thiazide diuretic + calcium channel blocker. 1, 2
• This three-drug regimen addresses hypertension through complementary mechanisms and is the standard approach for resistant hypertension. 2

Alternative: Consider Increasing Losartan Dose

While adding a diuretic is the preferred strategy, increasing losartan from 50 mg to 100 mg once daily is also a reasonable option if you prefer to optimize the ARB dose before adding a second agent. 1, 3 The FDA-approved maximum dose for hypertension is 100 mg daily. 3 However, current guidelines favor early combination therapy over monotherapy dose escalation because it achieves better blood pressure control. 2

Critical Safety Considerations

• Never combine losartan with an ACE inhibitor (such as enalapril or lisinopril), as dual renin-angiotensin system blockade increases the risk of hyperkalemia, syncope, and acute kidney injury by 2–3-fold without added cardiovascular benefit. 1, 2, 5
• Watch for hypokalemia and hyponatremia when adding thiazide diuretics, particularly in elderly patients. 1
• Measure blood pressure in both sitting and standing positions to detect orthostatic hypotension, especially in patients over 65 years. 2

Common Pitfalls to Avoid

• Do not rely solely on increasing the losartan dose to 100 mg as monotherapy—combination therapy is more effective. 2
• Do not add a beta-blocker as the second agent unless there are compelling indications (angina, post-MI, heart failure, atrial fibrillation), because beta-blockers are less effective than calcium channel blockers or diuretics for stroke prevention. 2
• Do not delay treatment intensification—persistent systolic pressures in the 140s–150s increase cardiovascular risk and require prompt action. 2