Which is more potent as an antihypertensive medication, Azilsartan (angiotensin II receptor antagonist) or Olmesartan (angiotensin II receptor antagonist), for a general adult population with hypertension and no underlying medical conditions such as impaired renal function or hyperkalemia?

Azilsartan is More Potent Than Olmesartan

Azilsartan medoxomil provides superior blood pressure reduction compared to olmesartan medoxomil, with an additional 4-8 mm Hg reduction in systolic blood pressure at maximum approved doses. 1

Evidence from Head-to-Head Trials

The most definitive evidence comes from a large randomized controlled trial using 24-hour ambulatory blood pressure monitoring (ABPM), which is the gold standard for assessing antihypertensive efficacy:

• Azilsartan 80 mg once daily reduced 24-hour mean systolic BP by 14.3 mm Hg (placebo-adjusted), compared to olmesartan 40 mg which reduced it by 11.7 mm Hg (P=0.009 for superiority) 2
• This represents a 2.6 mm Hg greater reduction with azilsartan at maximum approved doses 2
• For clinic systolic BP measurements, azilsartan 80 mg was also superior to olmesartan 40 mg across all measured timepoints 2

Meta-Analysis Confirmation

A 2019 meta-analysis of five trials including 1,402 patients confirmed these findings:

• Azilsartan reduced office systolic BP by an additional 2.15 mm Hg compared to olmesartan (95% CI: -3.78 to -0.53 mm Hg, P<0.01) 3
• When comparing equivalent doses (e.g., azilsartan 40 mg vs olmesartan 40 mg), azilsartan still provided 2.24 mm Hg greater systolic BP reduction (P<0.05) 3
• No significant difference was found in diastolic BP reduction between the two agents 3

Clinical Context from Guidelines

The American Heart Association's 2018 statement on resistant hypertension specifically highlights this difference:

• 24-hour ABPM studies demonstrate that azilsartan medoxomil provides on average an additional 4-8 mm Hg further systolic BP reduction over other ARBs including olmesartan 1
• This makes azilsartan particularly valuable when optimizing therapy in patients with resistant hypertension or those requiring maximal BP reduction 1

Real-World Comparative Study

A 2017 multicenter randomized trial (MUSCAT-4) comparing olmesartan 20 mg with azilsartan 20 mg showed:

• Both agents reduced BP effectively with similar tolerability 4
• No statistically significant differences were found between groups at this lower dose range 4
• This suggests the superiority of azilsartan is most pronounced at maximum approved doses (azilsartan 80 mg vs olmesartan 40 mg) 4

Safety Profile

Both agents demonstrated similar safety and tolerability profiles across all major trials, with no increase in adverse events despite azilsartan's greater BP-lowering efficacy 2. The most common side effects for both drugs include headache and dizziness, with low discontinuation rates 5, 6.

Practical Implications

• For patients requiring maximal ARB efficacy, azilsartan 80 mg is the superior choice over olmesartan 40 mg 1, 2
• The difference is clinically meaningful (2-8 mm Hg systolic BP reduction), as even small BP reductions translate to cardiovascular risk reduction 2, 3
• At lower doses (20-40 mg range), the difference between agents may be less pronounced 4
• Cost and availability may be practical considerations, but efficacy data clearly favor azilsartan at maximum doses 5, 2