Switching from Maximum Dose Losartan to Another ARB
For patients on maximum losartan (100 mg daily for hypertension, or 150 mg daily for heart failure), switching to candesartan or valsartan can provide superior efficacy, with valsartan 160 mg twice daily (320 mg total) being the preferred choice based on the most robust clinical trial evidence. 1, 2
Evidence for Switching ARBs
Losartan's Limitations at Maximum Dose
The HEAAL trial demonstrated that even at 150 mg daily (higher than the standard 100 mg maximum for hypertension), losartan showed a 10% relative risk reduction in death or heart failure hospitalization compared to 50 mg daily, suggesting dose-dependent benefits but still leaving room for improvement with more potent ARBs. 3, 4
For heart failure specifically, the European Society of Cardiology recommends losartan 150 mg as the target dose, acknowledging that the standard 50-100 mg doses appear inferior to ACE inhibitors for mortality reduction. 4
Superior ARB Options
Valsartan is the strongest alternative:
- Target dose: 160 mg twice daily (320 mg total daily) 1, 2
- The Val-HeFT trial showed a 13.2% reduction in cardiovascular mortality and morbidity at doses up to 320 mg/day 2
- VALIANT trial demonstrated valsartan 160 mg twice daily was noninferior to captopril for mortality outcomes post-MI 2
- Provides sustained AT1-receptor blockade over 24 hours at the 160 mg dose 2
Candesartan is the second choice:
- Target dose: 32 mg once daily 1
- CHARM Alternative trial showed improved outcomes in patients intolerant to ACE inhibitors 1
- Reduced hospitalizations by 3 per 100 patients per year in heart failure patients 5
Dosing Strategy When Switching
Do NOT start at the highest dose. 1, 2
For Valsartan:
- Start at 40-80 mg once or twice daily (not 320 mg) 1, 6
- Titrate every 2 weeks, doubling the dose 1, 2
- Target: 160 mg twice daily (320 mg total) 1, 2
- Monitor blood pressure (including postural), renal function, and potassium within 1-2 weeks after each dose change 1, 2
For Candesartan:
Critical Safety Monitoring
Check within 1-2 weeks after initiation or dose increases: 1, 2
- Serum creatinine/eGFR (acceptable if creatinine increases up to 50% above baseline or to 3 mg/dL) 2
- Serum potassium (caution if K+ >5.0 mmol/L) 2
- Blood pressure in sitting and standing positions 4
High-risk patients requiring closer surveillance: 1
- Systolic BP <80 mm Hg
- Low serum sodium
- Diabetes mellitus
- Impaired renal function (creatinine >2.5 mg/dL or eGFR <30 mL/min/1.73 m²) 2
Absolute Contraindications to Combination Therapy
Never combine ARBs with ACE inhibitors - this increases hyperkalemia and renal dysfunction risk without mortality benefit, as demonstrated in the VALIANT trial. 1, 2
Avoid triple combination of ARB + ACE inhibitor + aldosterone antagonist - this is potentially harmful. 1
When Switching May NOT Be Beneficial
If the patient has preserved ejection fraction (diastolic heart failure), the evidence for ARB superiority is less robust, and switching may not provide additional benefit. 5, 7
If blood pressure remains uncontrolled on maximum losartan, consider adding hydrochlorothiazide 12.5-25 mg daily rather than switching ARBs, as combination therapy provides additive effects. 4
Common Pitfall to Avoid
Underdosing is widespread - less than 25% of patients are ever titrated to target ARB doses in clinical practice. 4, 2 The benefit of switching ARBs is only realized if you actually titrate to the evidence-based target doses (valsartan 320 mg daily or candesartan 32 mg daily), not if you switch and remain at subtherapeutic doses.