A 62-year-old woman with hypertension on losartan 50 mg daily has uncontrolled blood pressure; which additional antihypertensive medication should be added?

Management of Uncontrolled Hypertension on Losartan 50 mg Daily

Add a calcium channel blocker (amlodipine 5–10 mg daily) or a thiazide-like diuretic (chlorthalidone 12.5–25 mg daily) as the second antihypertensive agent to achieve guideline-recommended dual therapy. 1

Preferred Second-Line Options

Option 1: Calcium Channel Blocker (Preferred for Most Patients)

• Adding amlodipine 5–10 mg once daily provides complementary vasodilation through calcium channel blockade combined with renin-angiotensin system inhibition from losartan, demonstrating superior blood pressure control compared to either agent alone. 1
• This combination is particularly beneficial for patients with diabetes, chronic kidney disease, heart failure, or coronary artery disease. 1
• Amlodipine may attenuate peripheral edema when combined with an ARB like losartan. 1

Option 2: Thiazide-Like Diuretic

• Adding chlorthalidone 12.5–25 mg once daily (preferred over hydrochlorothiazide due to longer duration of action and superior cardiovascular outcomes) creates an ARB + diuretic regimen that addresses volume-dependent hypertension. 2, 3
• This combination is particularly effective in elderly patients, Black patients, and those with volume-dependent hypertension. 2
• Chlorthalidone provides superior 24-hour blood pressure control compared to hydrochlorothiazide. 2

Dose Optimization Before Adding Third Agent

• Before adding a third medication, consider increasing losartan from 50 mg to 100 mg daily, as the HEAAL trial demonstrated that losartan 150 mg daily was superior to 50 mg daily for cardiovascular outcomes with a 10% relative risk reduction. 1
• For hypertension management specifically, 100 mg is considered the maximum effective dose. 1
• Losartan 50–100 mg once daily as monotherapy lowers blood pressure to a similar degree as enalapril, atenolol, and felodipine. 4

Progression to Triple Therapy

• If blood pressure remains uncontrolled after optimizing dual therapy (losartan 100 mg + amlodipine 10 mg OR losartan 100 mg + chlorthalidone 25 mg), add the third agent from the remaining class to create guideline-recommended triple therapy: ARB + calcium channel blocker + thiazide diuretic. 1
• This triple combination targets three complementary mechanisms: renin-angiotensin system blockade, vasodilation, and volume reduction. 2

Blood Pressure Targets and Monitoring

• Target blood pressure is <140/90 mmHg minimum, ideally <130/80 mmHg. 1
• Reassess blood pressure within 2–4 weeks after any medication adjustment. 1
• Aim to achieve target blood pressure within 3 months of treatment modification. 1
• Check serum potassium and creatinine 2–4 weeks after adding or uptitrating the ARB or adding a diuretic. 1

Special Population Considerations

• For Black patients specifically, the combination of calcium channel blocker + thiazide diuretic may be more effective than calcium channel blocker + ARB. 1

Lifestyle Modifications (Adjunctive)

• Reinforce sodium restriction to <2 g/day, which can provide additive blood pressure reductions of 5–10 mmHg. 1
• Weight management, regular aerobic exercise (≥30 minutes most days), and alcohol limitation to <100 g/week are recommended. 1

Critical Pitfalls to Avoid

• Do not combine losartan with an ACE inhibitor, as dual renin-angiotensin system blockade increases adverse events (hyperkalemia, acute kidney injury) without additional cardiovascular benefit. 2
• Do not add a beta-blocker as the second agent unless there are compelling indications (angina, post-myocardial infarction, heart failure with reduced ejection fraction, or atrial fibrillation requiring rate control). 2
• Do not delay treatment intensification—uncontrolled hypertension requires prompt action within 2–4 weeks to reduce cardiovascular risk. 2
• Verify medication adherence before escalating therapy, as non-adherence is the most common cause of apparent treatment resistance. 2

Tolerability Profile

• Losartan is very well tolerated, with dizziness being the only drug-related event reported more frequently than placebo. 4
• First-dose hypotension is uncommon with losartan. 4
• Cough occurs significantly less often with losartan than with ACE inhibitors, making it an excellent alternative for patients with ACE inhibitor-related cough. 4, 5
• The overall rate of patient withdrawal from losartan therapy due to adverse experiences is lower (2.3%) than placebo (3.7%). 6