What is the appropriate next step in managing a 52-year-old man with hypertension whose blood pressure remains elevated at 168/92 mmHg while taking losartan 50 mg daily?

Management of Uncontrolled Hypertension on Losartan 50 mg

Increase losartan to 100 mg once daily as the immediate next step, then reassess blood pressure in 2–4 weeks before adding a second agent. 1, 2, 3, 4

Rationale for Dose Escalation First

• The FDA-approved dosing for hypertension allows titration from the starting dose of 50 mg up to a maximum of 100 mg once daily based on blood pressure response. 4
• The 2024 ESC guidelines and current best practice recommend maximizing the first-line agent before adding combination therapy in patients with grade 1 hypertension (systolic 140–159 mmHg). 1, 3
• Clinical trial data demonstrate that losartan 100 mg once daily produces significantly greater blood pressure reduction than 50 mg once daily, with ambulatory monitoring showing mean reductions of 9.9/6.4 mmHg versus 9.2/6.9 mmHg respectively. 5
• At 168/92 mmHg, this patient has grade 1 hypertension and does not require immediate dual therapy, which is reserved for grade 2 hypertension (≥160/100 mmHg). 1, 2

Step-by-Step Management Algorithm

Step 1: Verify Adherence and Exclude Secondary Causes

• Before dose escalation, confirm medication adherence through direct questioning, as non-adherence is the most common cause of apparent treatment failure. 1, 3
• Rule out white-coat hypertension with home blood pressure monitoring (target <135/85 mmHg at home corresponds to <140/90 mmHg in office). 1, 2
• Screen for secondary causes if resistant hypertension develops: obstructive sleep apnea, excessive alcohol intake, renal artery stenosis, primary aldosteronism, and inadequate sodium restriction. 1

Step 2: Increase Losartan to 100 mg Once Daily

• Titrate losartan from 50 mg to 100 mg once daily immediately if adherence is confirmed. 1, 2, 3, 4
• Reassess blood pressure every 2–4 weeks during titration, aiming for a target of <130/80 mmHg within 3 months. 1, 2
• Monitor serum creatinine and potassium within 1–2 weeks after dose increase, especially given the patient's hypertension (which suggests possible underlying renal involvement). 1, 2

Step 3: Add Combination Therapy if BP Remains ≥140/90 mmHg

• If blood pressure remains uncontrolled after 4–8 weeks on losartan 100 mg daily, add hydrochlorothiazide 12.5–25 mg once daily as the preferred second agent. 1, 2, 6, 3, 4
• Alternative second-line options include a dihydropyridine calcium channel blocker (e.g., amlodipine 5–10 mg daily) or indapamide 2.5 mg daily. 1, 6
• Strongly prefer single-pill fixed-dose combinations (losartan/HCTZ) to improve adherence, which is markedly better than separate pills. 1, 2
• The addition of HCTZ 12.5 mg to losartan 50 mg produces an additional placebo-adjusted reduction of approximately 15.5/9.2 mmHg. 2, 5

Step 4: Escalate to Triple Therapy if Needed

• If BP remains ≥140/90 mmHg on dual therapy (losartan 100 mg + HCTZ 25 mg), add a dihydropyridine calcium channel blocker to create triple therapy (ARB + thiazide + CCB). 1, 2
• For resistant hypertension (uncontrolled on triple therapy), add spironolactone 25 mg daily as the fourth agent, which is the most effective add-on in this setting. 1

Target Blood Pressure Goals

• Aim for <130/80 mmHg in this 52-year-old man to reduce cardiovascular risk, which is the 2024 ESC guideline target for most adults. 1, 2
• The minimum acceptable target is <140/90 mmHg, but lower targets provide greater cardiovascular protection if well tolerated. 1, 3

Critical Safety Considerations

• Never combine losartan with an ACE inhibitor or direct renin inhibitor (aliskiren), as dual renin-angiotensin system blockade increases the risk of hyperkalemia, syncope, and acute kidney injury by 2–3-fold without cardiovascular benefit. 1, 2, 4
• Monitor for hyperkalemia, especially if the patient has diabetes, chronic kidney disease, or is taking potassium-sparing agents or NSAIDs. 2, 4
• Losartan is absolutely contraindicated in pregnancy due to serious fetal toxicity; ensure contraception counseling if applicable. 2, 4

Common Pitfalls to Avoid

• Do not add a second agent before maximizing losartan to 100 mg daily in grade 1 hypertension, as this represents suboptimal monotherapy dosing. 3
• Do not rely solely on office blood pressure measurements; use home monitoring to exclude white-coat hypertension and confirm true uncontrolled hypertension. 1
• Do not add a beta-blocker as second-line therapy unless there is a compelling indication (heart failure, post-MI, angina, atrial fibrillation), as beta-blockers are less effective than CCBs or diuretics for stroke prevention. 1, 2
• Avoid premature discontinuation for mild creatinine elevations (0.1–0.3 mg/dL increase is expected hemodynamic effect, not tubular injury). 2

Monitoring Schedule

• Recheck blood pressure in 2–4 weeks after increasing to losartan 100 mg. 1, 2, 3
• Measure serum creatinine and potassium within 1–2 weeks of dose escalation. 1, 2
• Once at target BP, monitor blood pressure at least every 3–6 months and renal function/electrolytes annually. 2