What is the best Angiotensin Receptor Blocker (ARB) for a patient with hypertension, possibly with comorbidities such as diabetes or kidney disease?

Best ARB Selection for Hypertension

For patients with diabetic nephropathy and macroalbuminuria, losartan or irbesartan are the preferred ARBs, with losartan being the only ARB with FDA-approved indication specifically for reducing hard renal endpoints in type 2 diabetic nephropathy. 1

Evidence-Based Selection Algorithm

For Diabetic Kidney Disease with Macroalbuminuria (≥300 mg/g)

• Losartan is the first-choice ARB based on the landmark RENAAL trial, which demonstrated a 16% reduction in the composite endpoint of doubling serum creatinine, ESRD, or death, with 25% reduction in sustained doubling of serum creatinine and 29% reduction in ESRD 1

• Irbesartan is equally effective based on the IDNT trial, showing similar renoprotective efficacy in type 2 diabetic nephropathy with macroalbuminuria 1, 2

• Both losartan and irbesartan demonstrated superiority over other antihypertensive classes in slowing GFR decline and preventing kidney failure 1, 2

For Diabetic Kidney Disease with Microalbuminuria (30-299 mg/g)

• Either ACE inhibitor or ARB is recommended as first-line therapy 3

• If ACE inhibitor is not tolerated (typically due to cough), substitute with an ARB 3

• Irbesartan has specific evidence for preventing progression from microalbuminuria to macroalbuminuria in the IRMA study 2

For Hypertension WITHOUT Albuminuria

• ARBs are NOT superior to other first-line agents (thiazide-like diuretics or dihydropyridine calcium channel blockers) in the absence of albuminuria 3

• Consider usual first-line drugs (thiazide-like diuretics, dihydropyridine calcium channel blockers) as they provide equivalent cardiovascular protection 3

For Specific Comorbidities

• Atrial fibrillation: ARBs may reduce AF recurrence 3

• Heart failure (preserved EF): Add ARB for incremental BP control after diuretics 3

• Stable ischemic heart disease: ACE inhibitor or ARB recommended 3

• Post-MI: ACE inhibitor or ARB recommended 3

• Cardiovascular risk reduction in patients ≥55 years unable to take ACE inhibitors: Telmisartan 80 mg daily is FDA-approved for reducing risk of MI, stroke, or cardiovascular death 4

Practical Dosing Strategy

• Losartan: Start 50 mg daily, titrate to 100 mg daily if BP goal not achieved and medication tolerated 1

• Irbesartan: Dosing should be maximized for renoprotection, as the effect is dose-dependent 1, 5

• Telmisartan: 80 mg once daily for cardiovascular risk reduction 4

• The renoprotective effect is dose-dependent; higher doses provide greater protection against CKD progression 1

Combination Therapy Considerations

• Enhance efficacy with thiazide or loop diuretics, as 60-90% of patients in major ARB trials used concomitant diuretics 1

• Multiple-drug therapy is generally required to achieve BP targets, particularly in diabetic kidney disease 3

• NEVER combine ARB + ACE inhibitor, as this increases adverse events (hyperkalemia, syncope, AKI) without mortality benefit 3, 1, 6

• NEVER combine ARB + direct renin inhibitor due to lack of added benefit and increased adverse events 3

Critical Monitoring Requirements

• Monitor serum creatinine/eGFR and potassium within 7-14 days after initiation or dose change 3

• Continue monitoring at least annually for patients on ARB therapy 3

• In patients receiving ARB therapy, continuation as kidney function declines to eGFR <30 mL/min/1.73 m² may provide cardiovascular benefit without significantly increasing risk of end-stage kidney disease 3

Absolute Contraindications

• Do not use ARBs in pregnancy 1

• Avoid in symptomatic hypotension 1

• Avoid in uncontrolled hyperkalemia 1

• Avoid in bilateral renal artery stenosis 1

Common Pitfalls to Avoid

• Do not prescribe ARBs to normotensive patients without albuminuria to prevent CKD development, as trials showed no benefit in preventing diabetic glomerulopathy in this population 1, 6

• Do not substitute other ARBs for losartan or irbesartan in diabetic nephropathy without recognizing that only these two have proven hard renal endpoint data 1, 2

• Telmisartan provides superior reductions in proteinuria compared to losartan when blood pressures are equalized, likely due to higher receptor affinity, longer plasma half-life, and higher lipophilicity 7

• Losartan has unique uricosuric effects not seen in other ARBs, which may be beneficial in patients with hyperuricemia 8