Are Angiotensin Receptor Blockers (ARBs) more effective than Angiotensin-Converting Enzyme (ACE) inhibitors for treating hypertension and heart failure in patients with various medical histories and comorbidities?

Are ARBs Better Than ACE Inhibitors?

No, ARBs are not better than ACE inhibitors—ACE inhibitors remain the first-line therapy for heart failure with reduced ejection fraction, post-myocardial infarction, and hypertension with compelling indications, while ARBs serve as equally effective alternatives primarily for patients who cannot tolerate ACE inhibitors due to cough or angioedema. 1, 2

Evidence-Based Hierarchy

ACE Inhibitors as First-Line Therapy

ACE inhibitors are the preferred initial choice based on extensive clinical trial evidence demonstrating consistent mortality and morbidity reduction across the cardiovascular continuum. 1

• ACE inhibitors have been shown in large randomized controlled trials to reduce morbidity and mortality in patients with heart failure with reduced ejection fraction (HFrEF) with mild, moderate, or severe symptoms, with or without coronary artery disease 1
• Benefits include decreased heart failure progression, reduced hospitalizations, and lower mortality rates consistently demonstrated across the clinical spectrum from asymptomatic to severely symptomatic heart failure 1
• The American College of Cardiology recommends ACE inhibitors as first-line therapy for heart failure with reduced ejection fraction, post-myocardial infarction patients, and patients with diabetic nephropathy 2

ARBs as Equivalent Alternatives (Not Superior)

ARBs produce similar hemodynamic, neurohormonal, and clinical effects to ACE inhibitors but are recommended specifically when ACE inhibitors cannot be tolerated. 1, 2

• ARBs have been shown to reduce mortality and heart failure hospitalizations in patients with HFrEF in large randomized controlled trials 1
• Similar benefits have been shown for ARBs in populations with mild-to-moderate heart failure who are unable to tolerate ACE inhibitors 1
• The ONTARGET trial demonstrated that ARBs are equivalent (non-inferior) to ACE inhibitors in preventing cardiovascular mortality, morbidity, myocardial infarction, and stroke, but not superior 3, 4
• Meta-analysis of hypertensive patients with myocardial infarction or heart failure showed no significant differences between ACE inhibitors and ARBs for recurrence of MI, hospitalization for heart failure, cardiovascular mortality, or cardiovascular events 5

Clinical Decision Algorithm

When to Use ACE Inhibitors (First-Line)

Start with ACE inhibitors in the following scenarios: 1, 2

• All patients with current or prior symptoms of chronic HFrEF (Class I, Level of Evidence A) 1
• Post-myocardial infarction patients with left ventricular ejection fraction ≤40% (Class I, Level of Evidence A) 1, 2
• Patients with hypertension and diabetes 2
• Patients with albuminuria (UACR ≥30 mg/g) to reduce progressive kidney disease 2
• Patients with structural cardiac abnormalities including left ventricular hypertrophy 1

When to Switch to ARBs

ARBs are recommended as alternatives in these specific situations: 1

• Patients intolerant to ACE inhibitors because of cough (occurs in up to 20% of patients) 1, 2
• Patients who develop angioedema with ACE inhibitors (occurs in <1% but more frequently in Black patients and women) 1, 2
• Patients already tolerating ARBs for other indications who subsequently develop heart failure 1

Critical caveat: Although ARBs are alternatives for ACE inhibitor-induced angioedema, caution is advised because some patients have also developed angioedema with ARBs 1

Side Effect Profile Differences

ACE Inhibitor Side Effects

• Dry cough: Up to 20% of patients due to kininase inhibition and increased bradykinin levels 1, 2
• Angioedema: <1% of patients, but more frequent in Black patients and women 1, 2
• Potential benefit: Kininase inhibition may produce beneficial vasodilatory effects 1

ARB Side Effects

• Significantly lower incidence of cough and angioedema compared to ACE inhibitors 1, 2, 6
• Study discontinuation due to adverse events was significantly more common with ACE inhibitors than ARBs 5
• ARBs do not inhibit kininase, eliminating the bradykinin-mediated cough 1

Shared Considerations for Both Classes

Monitoring Requirements

Both ACE inhibitors and ARBs require identical monitoring: 1, 2

• Check blood pressure, renal function (serum creatinine/eGFR), and serum potassium at baseline 2
• Recheck 1-2 weeks after each dose increment 1
• Monitor at 3 months, then at 6-month intervals 1
• Both should be given with caution to patients with low systemic blood pressure, renal insufficiency, or elevated serum potassium (>5.0 mEq/L) 1

Dosing Strategy

Start low and titrate upward for both classes: 1

• Begin at low doses and titrate upward with an attempt to use doses shown to reduce cardiovascular events in clinical trials 1
• If maximal doses are not tolerated, intermediate doses should be tried 1
• Abrupt withdrawal of ACE inhibition can lead to clinical deterioration and should be avoided 1

Common Pitfalls to Avoid

Combination Therapy Not Recommended

Do not routinely combine ACE inhibitors and ARBs: 2, 3

• The ONTARGET trial showed that combined RAS blockade achieved no further benefits in vascular high-risk patients and was associated with more adverse events 3
• The VALIANT trial demonstrated that dual RAS blockade did not further reduce events compared to monotherapy in post-MI patients 3
• Combination therapy increases risk of hypotension, renal insufficiency, and hyperkalemia without significant additional mortality benefit 3, 4

Timing When Switching

Allow adequate washout period when switching from ACE inhibitor to ARB: 2

• ARBs should not be initiated within 36 hours of discontinuing an ACE inhibitor due to risk of overlapping effects 2

Contraindications Apply to Both Classes

Both ACE inhibitors and ARBs are contraindicated in: 1, 7

• Pregnancy or patients planning to become pregnant 1
• Bilateral renal artery stenosis 7
• History of angioedema (use ARBs with extreme caution even if angioedema occurred with ACE inhibitor) 1

The Bottom Line

ACE inhibitors remain the evidence-based first choice for renin-angiotensin system blockade in heart failure, post-MI, and high-risk cardiovascular patients. 1, 2 ARBs are not superior but represent equally effective alternatives with better tolerability, specifically indicated when ACE inhibitors cause intolerable cough or angioedema. 1, 5 The choice should prioritize ACE inhibitors first unless specific intolerance develops, at which point ARBs provide equivalent cardiovascular protection with fewer side effects. 2, 5