What are alternative medications to Edarbi (azilsartan) for a patient with hypertension?

Alternative Medications to Edarbi (Azilsartan) for Hypertension

For patients requiring an alternative to Edarbi (azilsartan), other angiotensin receptor blockers (ARBs) such as olmesartan, valsartan, or candesartan are the most direct substitutes, though current guidelines recommend any of the four first-line drug classes—ARBs, ACE inhibitors, thiazide/thiazide-like diuretics, or long-acting dihydropyridine calcium channel blockers—as equally appropriate initial therapy. 1

Direct ARB Alternatives (Same Drug Class)

Since Edarbi is an ARB, the most pharmacologically similar alternatives include:

• Olmesartan 40 mg once daily - This was directly compared to azilsartan 80 mg in clinical trials, showing slightly less blood pressure reduction (approximately 3-4 mmHg less systolic BP lowering) but still effective antihypertensive efficacy 2, 3

• Valsartan 320 mg once daily - Also compared head-to-head with azilsartan, demonstrating approximately 5-6 mmHg less systolic BP reduction than azilsartan 80 mg, but proven cardiovascular outcome benefits in heart failure trials 2, 3

• Candesartan - Studies show azilsartan provides 2.6 mmHg greater diastolic BP reduction and 4.4 mmHg greater systolic BP reduction compared to candesartan, though both are effective 4

• Other ARBs including losartan, irbesartan, and telmisartan are also appropriate alternatives, with candesartan and valsartan having specific evidence for equivalence to ACE inhibitors in heart failure 1

First-Line Alternatives from Different Drug Classes

The WHO and ESC guidelines strongly recommend that any of the following three drug classes can serve as first-line therapy, making them appropriate alternatives: 1

ACE Inhibitors

• These are equally effective as ARBs for blood pressure control and cardiovascular outcomes 1
• Particularly useful in patients with heart failure, post-myocardial infarction, or diabetic nephropathy 1
• Common options include lisinopril, enalapril, or ramipril 5
• Main advantage over ARBs: lower cost and extensive cardiovascular outcomes data 1
• Main disadvantage: dry cough occurs in up to 10-20% of patients, which is why ARBs like azilsartan are often prescribed as alternatives 6

Long-Acting Dihydropyridine Calcium Channel Blockers

• Amlodipine is the most commonly used and has proven cardiovascular outcomes 1
• Particularly effective in black patients, who tend to have lower renin levels and respond less robustly to ARBs and ACE inhibitors as monotherapy 2
• Can be combined with azilsartan or used as an alternative 2
• Other options include felodipine and nifedipine extended-release 1

Thiazide or Thiazide-Like Diuretics

• Chlorthalidone and hydrochlorothiazide are both effective, with chlorthalidone having longer duration of action 1
• Chlorthalidone is available in fixed-dose combination with azilsartan (Edarbyclor), but can also be used as monotherapy or with other agents 7
• Thiazide-like diuretics (chlorthalidone, indapamide) may be preferred over hydrochlorothiazide for cardiovascular outcomes 1

Combination Therapy Considerations

If blood pressure is >20/10 mmHg above goal, combination therapy is recommended from the start, preferably as a single-pill combination to improve adherence: 1

• Azilsartan/chlorthalidone combination showed superior blood pressure reduction compared to olmesartan/hydrochlorothiazide 7
• If switching from azilsartan, consider ARB + thiazide-like diuretic, ARB + calcium channel blocker, or ACE inhibitor + calcium channel blocker combinations 1
• Avoid combining ACE inhibitors with ARBs—this increases adverse events without additional benefit 8

Special Population Considerations

Black Patients

• ARBs (including azilsartan) have approximately half the blood pressure-lowering effect as monotherapy in black patients compared to non-black patients 2
• Initial therapy should be a calcium channel blocker or thiazide-like diuretic, or combination of ARB + calcium channel blocker or ARB + diuretic 1

Patients with Heart Failure

• ARBs (candesartan, valsartan) and ACE inhibitors are equally effective and should be combined with beta-blockers (carvedilol, metoprolol succinate, bisoprolol) and diuretics 1, 8
• Loop diuretics preferred over thiazides in severe heart failure or renal impairment 1, 8
• Avoid non-dihydropyridine calcium channel blockers (verapamil, diltiazem) due to negative inotropic effects 1, 8

Patients with Chronic Kidney Disease

• ACE inhibitors and ARBs are preferred for renoprotection 1
• Azilsartan has been shown safe in patients with renal impairment 5
• Monitor renal function and potassium closely when initiating or switching therapy 1

Common Pitfalls to Avoid

• Do not use alpha-blockers (doxazosin) as alternatives—they increase heart failure risk and were stopped early in the ALLHAT trial 1, 8
• Avoid clonidine and moxonidine in patients with heart failure due to increased mortality risk 1, 8
• Do not combine ACE inhibitors with ARBs—this strategy increases adverse events without improving outcomes 8
• When switching from azilsartan to another ARB, expect slightly less blood pressure reduction (3-6 mmHg) based on comparative trials, and monitor accordingly 2, 3, 4

Target Blood Pressure Goals

• Standard target: <140/90 mmHg for most patients 1
• Lower target of <130/80 mmHg for patients with cardiovascular disease, diabetes, or chronic kidney disease 1
• Achieve target within 3 months of initiating or switching therapy 1