Maximum Dose of ARBs
The maximum doses of ARBs vary by specific agent: candesartan 32 mg once daily, valsartan 160 mg twice daily (320 mg total daily), losartan 100-150 mg once daily, olmesartan 40 mg once daily, and telmisartan 40-80 mg once daily, with these target doses established in landmark trials for heart failure and hypertension. 1
Evidence-Based Maximum Doses by Specific ARB
The maximum doses are derived from major clinical trials and vary significantly between agents:
Heart Failure Target Doses
- Candesartan: 32 mg once daily 1
- Valsartan: 160 mg twice daily (320 mg total daily dose) 1
- Losartan: 150 mg once daily (though 50-100 mg is more commonly used) 1
Hypertension Maximum Doses
- Valsartan: 320 mg once daily for hypertension (compared to 160 mg twice daily for heart failure) 2
- Losartan: 50-100 mg once daily, with some evidence supporting up to 150 mg 1, 3, 4
- Candesartan: 32 mg once daily 1
- Olmesartan: 40 mg once daily 5
Clinical Context for Dosing
Heart Failure Considerations
In heart failure with reduced ejection fraction, uptitration to target doses shown in clinical trials is critical for mortality and morbidity benefit. 1 The EMPHASIS-HF and other landmark trials established these specific doses as targets, with gradual uptitration recommended starting from lower initial doses (candesartan 4-8 mg, valsartan 40 mg twice daily). 1
Hypertension Considerations
For hypertension management, doses above 50-100 mg of losartan or 160 mg of valsartan once daily provide diminishing additional blood pressure reduction. 4 The addition of hydrochlorothiazide 12.5-25 mg produces greater antihypertensive effect than dose escalation beyond mid-range ARB doses. 1, 4
Post-Myocardial Infarction
Valsartan target dose is 160 mg twice daily when initiated as early as 12 hours post-MI, starting at 20 mg twice daily and uptitrating within 7 days as tolerated. 2
Duration of Action Differences
Not all ARBs maintain 24-hour efficacy at lower doses. 6 Losartan 25 mg once daily shows insufficient duration of action with morning-to-evening effect ratios of only 0.49/0.16 for systolic/diastolic blood pressure, while telmisartan, valsartan, and candesartan demonstrate more sustained 24-hour control. 6
Important Caveats
Combining ARBs with ACE inhibitors or direct renin inhibitors is contraindicated due to increased risk of hyperkalemia, syncope, and acute kidney injury without additional cardiovascular benefit. 1
Monitor serum creatinine, eGFR, and potassium at least annually when using ARBs, particularly at higher doses or in combination with diuretics or mineralocorticoid receptor antagonists. 1
Dose reduction is necessary for symptomatic hypotension or renal dysfunction, particularly in volume-depleted patients or those with bilateral renal artery stenosis. 2
Olmesartan maximum dose of 80 mg has been studied for sustained 24-hour renin-angiotensin system blockade in research settings, providing 76% blockade at trough, though 40 mg remains the FDA-approved maximum for clinical use. 5, 7