In an adult with uncomplicated hypertension, normal renal function, no history of angioedema and no cost constraints, should I start azilsartan or telmisartan as first‑line therapy, and would the recommendation change for an elderly patient with borderline renal impairment?

Azilsartan vs Telmisartan for Uncomplicated Hypertension

Direct Recommendation

For an adult with uncomplicated hypertension and normal renal function, start with telmisartan 40–80 mg once daily rather than azilsartan, because telmisartan provides equivalent 24-hour blood pressure control with a longer track record of cardiovascular safety data, while azilsartan's superior ABPM reductions have not translated into proven outcome benefits. For an elderly patient with borderline renal impairment, this recommendation remains unchanged—telmisartan is preferred because both agents are renin-angiotensin system (RAS) blockers and neither is the optimal first-line choice in this population; a thiazide-like diuretic (chlorthalidone) should be considered instead. 1

Guideline Context: ARBs Are Not Preferred First-Line Agents

General Population Without Compelling Indications

• The 2017 ACC/AHA and 2024 ESC guidelines endorse four first-line drug classes for uncomplicated hypertension: thiazide/thiazide-like diuretics, ACE inhibitors, ARBs, and long-acting dihydropyridine calcium-channel blockers. 2, 1
• Thiazide-like diuretics (especially chlorthalidone 12.5–25 mg daily) are the optimal first-line agents because they have the strongest cardiovascular outcome evidence, reducing heart failure by 38% compared with amlodipine and stroke by 15% compared with lisinopril in the ALLHAT trial of >50,000 participants. 1
• ARBs (including both telmisartan and azilsartan) are appropriate first-line options only when thiazides, ACE inhibitors, or calcium-channel blockers are contraindicated or not tolerated. 1, 3

Black Patients

• For Black adults without heart failure or chronic kidney disease, thiazide diuretics or calcium-channel blockers are preferred over ARBs because RAS inhibitors are approximately 30–36% less effective for stroke prevention in this population due to lower renin activity. 1, 4

Elderly and Borderline Renal Impairment

• For community-dwelling adults ≥65 years with systolic ≥130 mmHg, the target is <130 mmHg; thiazide-like diuretics remain the preferred first-line class because of superior cardiovascular outcomes. 1
• In patients with borderline renal impairment (eGFR 45–60 mL/min/1.73 m²), thiazide diuretics remain effective and should not be avoided; ARBs are reserved for those with albuminuria ≥300 mg/day or eGFR <45 mL/min/1.73 m². 1

Head-to-Head Comparison: Azilsartan vs Telmisartan

Azilsartan: Superior ABPM Reduction Without Outcome Data

• Azilsartan 40–80 mg once daily produces greater 24-hour ambulatory blood pressure reductions than valsartan, olmesartan, and candesartan in randomized controlled trials, with similar safety profiles. 5
• Azilsartan was superior to ramipril (an ACE inhibitor) in ABPM results and noninferior to amlodipine for sleep-time blood pressure control. 5
• The azilsartan + chlorthalidone combination was superior to other sartan + thiazide regimens for both blood pressure lowering and goal achievement. 5
• Critical limitation: Azilsartan was FDA-approved in 2011 and lacks long-term cardiovascular outcome trials demonstrating reductions in stroke, myocardial infarction, heart failure, or mortality. 5

Telmisartan: Proven 24-Hour Efficacy and Cardiovascular Safety

• Telmisartan 40–80 mg once daily provides effective 24-hour blood pressure control with a long elimination half-life (≈24 hours) ensuring sustained reductions during the last 6 hours of the dosing interval. 6, 7
• Telmisartan 80 mg was more effective than losartan 50 mg or valsartan 80 mg over the last 6 hours and the entire 24-hour interval. 7
• Telmisartan was as effective as amlodipine 5–10 mg, atenolol 50–100 mg, enalapril 5–20 mg, and lisinopril 10–40 mg in dose-titration studies. 7
• Telmisartan has extensive cardiovascular outcome data from large trials (e.g., ONTARGET, TRANSCEND) demonstrating long-term safety and efficacy in diverse populations, including the elderly and those with diabetes or mild-to-moderate renal impairment. 6
• Telmisartan displays favorable effects on insulin resistance, lipid levels, left ventricular hypertrophy, and renal function independent of blood pressure reduction. 6

Safety and Tolerability

• Both agents have placebo-like tolerability profiles; telmisartan causes significantly less dry cough than ACE inhibitors (e.g., lisinopril). 6, 7
• Azilsartan's safety profile is similar to placebo in clinical trials, but long-term real-world safety data are less robust than for telmisartan. 5

Practical Algorithm for ARB Selection

Step 1: Confirm ARB Is Appropriate

• If the patient has uncomplicated hypertension without diabetes, chronic kidney disease, or heart failure, reconsider starting with chlorthalidone 12.5–25 mg once daily instead of an ARB, because thiazides have superior cardiovascular outcome evidence. 1
• If the patient is Black without heart failure or CKD, start with chlorthalidone or amlodipine rather than any ARB. 1, 4

Step 2: Choose Between Azilsartan and Telmisartan

• If 24-hour ABPM data show inadequate control on telmisartan 80 mg, consider switching to azilsartan 40–80 mg for its superior ABPM reductions. 5
• For initial therapy in uncomplicated hypertension, start with telmisartan 40 mg once daily and titrate to 80 mg after 4 weeks if blood pressure remains ≥130/80 mmHg, because telmisartan has proven cardiovascular outcome benefits. 6, 7
• For elderly patients (≥65 years) or those with borderline renal impairment (eGFR 45–60 mL/min/1.73 m²), prefer telmisartan 40–80 mg over azilsartan due to its longer safety track record in these populations. 6, 8

Step 3: Escalate to Combination Therapy if Needed

• If blood pressure remains ≥130/80 mmHg after 4 weeks on telmisartan 80 mg or azilsartan 80 mg, add chlorthalidone 12.5–25 mg once daily or amlodipine 5–10 mg once daily as a single-pill combination. 1, 3
• For stage 2 hypertension (≥140/90 mmHg), initiate two-drug combination therapy immediately (ARB + thiazide or ARB + calcium-channel blocker) rather than starting with monotherapy. 1

Special Considerations for Borderline Renal Impairment

When to Use ARBs in Renal Impairment

• ARBs are first-line only when albuminuria ≥300 mg/day or eGFR <45 mL/min/1.73 m² to slow kidney disease progression. 1
• For eGFR 45–60 mL/min/1.73 m² without significant proteinuria, thiazide diuretics remain effective and are preferred over ARBs. 1

Monitoring in Renal Impairment

• After starting telmisartan or azilsartan, repeat serum creatinine, eGFR, and potassium within 1–2 weeks, after each dose increase, and then annually. 1
• An increase in serum creatinine up to 50% above baseline or to 3 mg/dL (whichever is greater) is acceptable and does not require discontinuation. 1
• Hold the ARB if serum potassium rises above 5.5 mmol/L or if eGFR declines by >30% from baseline. 1

Common Pitfalls to Avoid

• Do not start with an ARB in uncomplicated hypertension when chlorthalidone would provide superior cardiovascular protection. 1
• Do not combine telmisartan or azilsartan with an ACE inhibitor or another ARB; dual RAS blockade increases hyperkalemia and acute kidney injury without added cardiovascular benefit. 2, 3
• Do not use azilsartan solely because of its superior ABPM data when telmisartan has proven long-term cardiovascular outcome benefits. 6, 5
• Do not avoid thiazide diuretics in elderly patients or those with eGFR 45–60 mL/min/1.73 m²; they remain effective and are the preferred first-line class. 1
• Do not initiate ARB monotherapy in stage 2 hypertension (≥140/90 mmHg); start with a two-drug combination (ARB + thiazide or ARB + calcium-channel blocker) as a single-pill formulation. 1, 3