What to do when hypertension persists despite losartan (angiotensin II receptor antagonist) 100mg?

Management of Persistent Hypertension on Losartan 100mg

Add a calcium channel blocker (amlodipine 5mg daily) as the next step, followed by a thiazide-like diuretic (indapamide 2.5mg daily) if blood pressure remains uncontrolled. 1, 2

Step-Wise Treatment Algorithm

Step 1: Add Calcium Channel Blocker

• Start amlodipine 5mg once daily as second-line therapy in combination with your current losartan 100mg 3, 2
• This combination provides complementary mechanisms: losartan blocks the renin-angiotensin system while amlodipine relaxes vascular smooth muscle 2
• Reassess blood pressure after 2-4 weeks with a target of <130/80 mmHg 1
• Monitor for peripheral edema, the most common side effect of amlodipine 2

Step 2: Add Thiazide-Like Diuretic if Needed

• If blood pressure remains uncontrolled after 2-4 weeks, add indapamide 2.5mg daily as third-line therapy 3, 1, 2
• This creates a triple-therapy regimen (ARB + calcium channel blocker + diuretic) that addresses multiple pathways of blood pressure regulation 3
• Recheck renal function and serum electrolytes 1 week after starting the diuretic 3

Step 3: Consider Spironolactone as Fourth-Line

• If blood pressure remains ≥160/100 mmHg on three drugs including a diuretic, add spironolactone 25mg daily 3, 1, 4
• Only add spironolactone if serum potassium is <4.5 mmol/L and eGFR >45 mL/min/1.73m² 1, 2
• The PATHWAY-2 trial demonstrated spironolactone as the most effective fourth-line agent for resistant hypertension 4
• Monitor potassium levels closely: recheck at 1 and 4 weeks after initiation 3
• If potassium rises to >5.5 mmol/L, reduce dose to 25mg on alternate days; if >6.0 mmol/L, stop immediately 3

Important Monitoring Parameters

Blood Pressure Targets

• Target blood pressure is <130/80 mmHg according to current American Heart Association and American College of Cardiology guidelines 1
• Confirm uncontrolled hypertension with out-of-office measurements (home or ambulatory monitoring) before intensifying therapy 4
• If there is a marked difference (>20/10 mmHg) between clinic and home readings, repeat home monitoring with a target of <150/95 mmHg 3

Laboratory Monitoring

• Check renal function and serum electrolytes before adding each new medication 3, 1
• Recheck 1 week after starting any new antihypertensive agent 3
• Monitor at 1,3, and 6 months after achieving maintenance doses, then every 6 months 3

Critical Considerations and Pitfalls

Medication Adherence

• Verify adherence before escalating therapy - pseudo-resistant hypertension due to non-adherence is common 4
• Consider single-pill combination products to improve adherence 1
• Simplify to once-daily dosing whenever possible 1

Secondary Hypertension Screening

• If blood pressure remains uncontrolled on ≥3 drugs including a diuretic, screen for secondary causes 3, 1, 4
• Consider referral to a hypertension specialist at this point 3, 1
• Evaluate for renal artery stenosis, primary aldosteronism, pheochromocytoma, and obstructive sleep apnea 4

Lifestyle Modifications

• Reinforce sodium restriction (<2g/day), weight loss if overweight, regular physical activity, and alcohol moderation 4
• Review all medications for agents that can elevate blood pressure (NSAIDs, decongestants, stimulants, SNRIs) 1, 4
• Avoid NSAIDs as they reduce antihypertensive efficacy 1

Alternative Second-Line Options

When to Consider Alternatives

• Thiazide-like diuretics (indapamide 2.5mg) can be used as second-line instead of amlodipine if cost is a concern or if the patient has isolated systolic hypertension 2
• Beta-blockers are generally not preferred as second-line unless there are specific indications such as coronary artery disease, heart failure, or prior myocardial infarction 2

Special Population Considerations

Diabetes

• The losartan plus calcium channel blocker combination provides additional renoprotection in diabetic patients 2
• Target blood pressure remains <130/80 mmHg 1

Elderly Patients

• More careful dose titration may be required due to increased medication sensitivity 2
• The same blood pressure targets apply unless frailty or limited life expectancy warrant individualized goals 1

Hepatic Impairment

• Losartan dose should not exceed 25mg daily in patients with mild-to-moderate hepatic impairment 5
• Losartan has not been studied in severe hepatic impairment 5