When is an Angiotensin Receptor Blocker (ARB) a better option than an Angiotensin-Converting Enzyme Inhibitor (ACEI) for a patient with hypertension or heart failure?

When ARBs Are Better Than ACEIs

ARBs are definitively better than ACEIs when patients develop intolerable cough or angioedema from ACE inhibitor therapy, as ARBs provide equivalent cardiovascular outcomes with significantly fewer adverse effects. 1, 2

Primary Indication: ACEI Intolerance

ARBs should be prescribed as first-line therapy in the following situations:

• Patients who develop cough on ACEIs (occurs in up to 20% of patients due to bradykinin accumulation) 1, 3
• Patients with prior ACE inhibitor-induced angioedema (though caution is warranted as some patients develop angioedema with ARBs as well) 1, 4
• Patients already taking ARBs for other indications (e.g., hypertension, diabetic nephropathy) who subsequently develop heart failure 1

The evidence is clear: ARBs are associated with a much lower incidence of cough and angioedema compared to ACEIs, while maintaining equivalent efficacy for mortality and morbidity reduction in heart failure and post-MI patients. 1, 5, 2

Clinical Context: Heart Failure and Post-MI

When ARBs Are Reasonable Alternatives

For patients with heart failure and reduced ejection fraction (HFrEF):

• ARBs are reasonable as first-line alternatives to ACEIs, particularly for mild to moderate heart failure (NYHA class II-III) 1
• The CHARM-Alternative trial demonstrated that candesartan significantly reduced cardiovascular death and heart failure hospitalization in ACEI-intolerant patients 1

For post-MI patients:

• ARBs should be administered to patients without heart failure who are intolerant of ACEIs and have low left ventricular ejection fraction 1
• The VALIANT trial showed valsartan was noninferior to captopril for mortality outcomes in post-MI patients with LV dysfunction 1, 6

Important Caveat: ACEIs Remain First Choice

Despite equivalent outcomes in head-to-head comparisons, ACEIs remain the preferred first-line therapy for most patients with heart failure or post-MI with LV dysfunction, unless contraindicated or not tolerated. 1, 3 This recommendation persists in guidelines because:

• ACEIs have more extensive long-term outcome data across diverse populations 3, 7
• Meta-analyses suggest ACEIs (but not ARBs) significantly reduce all-cause mortality by 11% and cardiovascular mortality by 14% in heart failure patients 7
• ARBs do not inhibit kininase, potentially missing beneficial vasodilatory effects from bradykinin 1

Special Population: Women

Emerging evidence suggests ARBs may be preferentially beneficial in women:

• A large population-based study (19,698 patients ≥65 years) found women on ARBs had better survival than those on ACEIs, while men showed no survival difference between the two drug classes 1
• Women appeared more persistent with ARB therapy, likely due to fewer adverse effects 1
• The CHARM program showed women obtained significantly greater benefit from candesartan than men in reducing all-cause mortality, sudden death, and heart failure hospitalization 1

However, this finding has not been reproduced in prospective randomized trials, and current guidelines make no sex-specific recommendations. 1 Until confirmatory evidence emerges, this should inform but not dictate therapy selection in women with ACEI intolerance.

Practical Algorithm for Drug Selection

Step 1: Assess for absolute contraindications to both drug classes:

• Pregnancy or planned pregnancy 3
• Bilateral renal artery stenosis 3
• History of angioedema with both ACEIs and ARBs 1

Step 2: If no contraindications, start with ACEI:

• Initiate low-dose ACEI (captopril, enalapril, lisinopril, ramipril, or trandolapril) 3
• Monitor for cough, angioedema, hypotension, renal dysfunction, and hyperkalemia 3

Step 3: Switch to ARB if:

• Intolerable cough develops (most common reason) 1, 5, 2
• Angioedema occurs (permanently discontinue ACEI; use ARB with caution) 1, 4
• Patient already tolerating ARB for another indication 1

Step 4: Consider ARB as first-line in:

• Women with heart failure (based on observational data suggesting potential survival benefit) 1
• Patients with strong preference to avoid cough (ARBs have lower cough incidence) 2

Critical Warnings and Monitoring

Both ACEIs and ARBs share serious adverse effects requiring identical monitoring:

• Hyperkalemia (especially with concurrent potassium-sparing diuretics or aldosterone antagonists) 1
• Renal dysfunction (monitor creatinine within 1-2 weeks of initiation) 3
• Hypotension (particularly in volume-depleted patients) 1, 3

Angioedema risk with ARBs after ACEI-induced angioedema:

• Cross-reactivity occurs in 2-17% of patients 4
• Never restart the same ACEI after angioedema 4
• Use ARBs cautiously with close monitoring if switching after ACEI-induced angioedema 1, 4

Combination Therapy: Generally Not Recommended

Adding an ARB to ongoing ACEI therapy:

• Does not reduce mortality compared to ACEI alone 1, 8
• Increases risk of hyperkalemia, renal failure, and hypotension 8
• The VALIANT trial showed combination valsartan plus captopril had higher discontinuation rates due to adverse effects without mortality benefit 1

Exception: The CHARM-Added trial showed modest benefit in stable heart failure patients already on established ACEI therapy, reducing heart failure hospitalization by 1-3 per 100 patients per year, but with increased adverse effects. 1 This strategy is not routinely recommended given the availability of other evidence-based therapies (beta-blockers, mineralocorticoid receptor antagonists, SGLT2 inhibitors).

Bottom Line for Clinical Practice

Use ACEIs first unless the patient has already developed cough or angioedema, is already taking an ARB, or is a woman where observational data suggest potential ARB superiority. 1, 3, 2 ARBs provide equivalent cardiovascular protection with better tolerability, making them the clear choice when ACEI adverse effects occur. 2, 7