Will increasing olmesartan (angiotensin II receptor antagonist) from 20 to 25 mg be sufficient to reduce hypertension from 150/80 to 130/70?

Olmesartan Dose Increase: Insufficient for Target Blood Pressure

Increasing olmesartan from 20 mg to 25 mg will not help achieve the target blood pressure of 130/70 mmHg because 25 mg is not a standard dose—olmesartan is only available in 20 mg and 40 mg tablets, and the appropriate next step is to increase to 40 mg, which provides significantly greater blood pressure reduction than 20 mg. 1

Understanding Olmesartan Dosing

The FDA-approved dosing for olmesartan demonstrates a clear dose-response relationship:

• Starting dose: 20 mg once daily produces approximately 10/6 mmHg reduction over placebo 1
• Maximum dose: 40 mg once daily produces approximately 12/7 mmHg reduction over placebo 1
• Doses above 40 mg: Show little additional effect 1

There is no 25 mg dose of olmesartan available—the medication comes in 5 mg, 20 mg, and 40 mg tablets only. 1

Expected Blood Pressure Reduction

Your patient needs to reduce blood pressure from 150/80 mmHg to 130/70 mmHg, requiring a reduction of 20/10 mmHg.

Increasing to Olmesartan 40 mg:

• The increase from 20 mg to 40 mg provides an additional 2/1 mmHg reduction beyond the 20 mg dose 1
• This modest increase alone will not achieve the target of 130/70 mmHg 2
• Clinical studies show that uptitration from 20 mg to 40 mg results in additional mean reductions, but these are insufficient for a 20/10 mmHg drop 2

Recommended Treatment Strategy

The most effective approach is to add hydrochlorothiazide (HCTZ) to olmesartan rather than simply increasing the olmesartan dose. 3

Step-by-Step Algorithm:

1. Increase olmesartan to 40 mg once daily as the first step 1, 2

2. Add HCTZ 12.5-25 mg once daily if blood pressure remains above target after 2-4 weeks 3, 4

   • The combination of olmesartan 20 mg/HCTZ 12.5 mg reduces 24-hour DBP by an additional 1.9 mmHg and SBP by 3.9 mmHg compared to olmesartan alone 4
   • The combination of olmesartan 20 mg/HCTZ 25 mg reduces 24-hour DBP by 3.7 mmHg and SBP by 7.4 mmHg compared to olmesartan alone 4
   • Olmesartan 40 mg/HCTZ 12.5 mg reduces SeDBP by 18.9 mmHg and SeSBP significantly more than olmesartan 40 mg alone 5

3. Target blood pressure: <130/80 mmHg per current guidelines 3

4. Reassess within 2-4 weeks after medication changes 6, 7

Why Combination Therapy is Superior

Adding a thiazide diuretic to an ARB provides complementary mechanisms of action—the ARB blocks the renin-angiotensin system while the diuretic reduces volume, resulting in synergistic blood pressure lowering. 3

• Response rates (achieving target BP) approximately doubled when HCTZ was added to olmesartan 20 mg (57.6% with 12.5 mg HCTZ and 69.5% with 25 mg HCTZ) 4
• BP goal rates at 8 weeks were 58.5% with olmesartan 40 mg/HCTZ 12.5 mg versus 44.3% with olmesartan 40 mg alone 5
• Patients inadequately controlled on olmesartan 40 mg who had HCTZ 25 mg added achieved additional reductions of 5.3/7.4 mmHg (DBP/SBP) 8

Critical Clinical Considerations

Monitoring Requirements:

• Check serum potassium and creatinine 2-4 weeks after adding HCTZ to detect hypokalemia 3
• Monitor for hyperuricemia in patients with gout history 3

If Triple Therapy Needed:

• If olmesartan 40 mg/HCTZ 25 mg fails to achieve target, add a calcium channel blocker (amlodipine 5-10 mg) as the third agent 3, 6, 7
• This represents guideline-recommended triple therapy: ARB + thiazide + calcium channel blocker 3

Common Pitfall to Avoid:

Do not assume that simply doubling the ARB dose will achieve target blood pressure—the dose-response curve for ARBs flattens at higher doses, and combination therapy is more effective than monotherapy dose escalation for achieving significant blood pressure reductions. 2, 8