Second-Line Antihypertensive Therapy After Losartan
Add a calcium channel blocker (CCB), specifically amlodipine 5 mg once daily, as your second-line agent for this patient already on losartan 100 mg. 1
Rationale for CCB as Second-Line
The most recent 2024 ESC guidelines explicitly recommend combination therapy including a CCB combined with a RAS blocker (like losartan) for patients requiring additional blood pressure control. 1 This represents the current standard of care based on the highest quality guideline evidence.
The 2017 ACC/AHA guidelines similarly classify CCBs as primary agents alongside ARBs, making them the logical next step when monotherapy with an ARB fails to achieve blood pressure targets. 1
Specific Drug and Dosing
- Start amlodipine 2.5-5 mg once daily 1
- Amlodipine is preferred among dihydropyridine CCBs due to its once-daily dosing, proven cardiovascular outcomes, and extensive safety data 1
- The combination of losartan plus amlodipine provides complementary mechanisms: ARB blocks the renin-angiotensin system while CCB provides direct vasodilation 2
Alternative Second-Line Options (If CCB Not Suitable)
If the patient cannot tolerate a CCB (due to pedal edema, which occurs more commonly in women), consider:
- Thiazide or thiazide-like diuretic: Chlorthalidone 12.5-25 mg once daily is preferred over hydrochlorothiazide due to its longer half-life and proven cardiovascular risk reduction 1
- The combination of losartan plus hydrochlorothiazide has been extensively studied and shows additive blood pressure lowering effects 3, 4, 5
Why Not Other Options
- ACE inhibitors should NOT be added to losartan, as combining two RAS blockers (ARB + ACE inhibitor) increases the risk of hyperkalemia and acute renal failure without additional benefit 1
- Beta-blockers are not recommended as first-line or routine second-line agents unless the patient has specific indications like ischemic heart disease or heart failure 1
- Spironolactone is reserved for resistant hypertension (failure of three-drug therapy including a diuretic) 1
Monitoring After Initiation
- Reassess blood pressure after 2-4 weeks of adding the CCB 6
- Target blood pressure is <130/80 mmHg 6, 7
- Monitor for CCB-related pedal edema, which is dose-dependent and more common in women 1
- If using a thiazide instead, monitor electrolytes (sodium, potassium), uric acid, and calcium levels 1
Common Pitfalls to Avoid
- Do not combine losartan with an ACE inhibitor or direct renin inhibitor - this increases adverse effects without improving outcomes 1
- Avoid non-dihydropyridine CCBs (diltiazem, verapamil) as initial CCB choice, as these have more drug interactions and are contraindicated in heart failure with reduced ejection fraction 1
- Do not use hydrochlorothiazide doses >25-50 mg daily - higher doses increase metabolic side effects without additional blood pressure benefit 1
If Blood Pressure Remains Uncontrolled
If blood pressure remains elevated after optimizing the two-drug combination (losartan + CCB), add a thiazide diuretic as the third agent, creating the preferred triple therapy combination recommended by guidelines. 1, 6