Can Angiotensin-Converting Enzyme (ACE) inhibitors and Angiotensin Receptor Blockers (ARBs) be used together?

ACE Inhibitors and ARBs Should Not Be Used Together

The combined use of ACE inhibitors and ARBs should be avoided as clinical trials have found no benefits on cardiovascular disease or chronic kidney disease outcomes, while showing higher adverse event rates including hyperkalemia and acute kidney injury. 1

Evidence Against Dual RAAS Blockade

The evidence against combining these medication classes is strong and consistent across multiple guidelines:

• The American Diabetes Association's Standards of Medical Care clearly states that "the combined use of ACE inhibitors and ARBs should be avoided" due to lack of benefit and increased risk of adverse events 1

• The ACC/AHA hypertension guidelines explicitly warn against simultaneous administration of renin-angiotensin system blockers, noting that it "increases cardiovascular and renal risk" 1

• The FDA drug labels for both ARBs (losartan) and ACE inhibitors (lisinopril) contain specific warnings against dual blockade of the renin-angiotensin system, stating it is "associated with increased risks of hypotension, hyperkalemia, and changes in renal function (including acute renal failure)" 2, 3

• The European Society of Cardiology/European Society of Hypertension guidelines similarly recommend that "the combination of 2 renin-angiotensin system blockers is not recommended" 1

Specific Risks of Dual Therapy

When ACE inhibitors and ARBs are used together, patients face several significant risks:

• Hyperkalemia: Both drug classes can increase serum potassium levels, and this effect is amplified when used together 2, 3

• Acute kidney injury: The Veterans Affairs Nephropathy in Diabetes (VA NEPHRON-D) trial demonstrated increased incidence of acute kidney injury with combination therapy 2

• Hypotension: The combined effect can lead to excessive blood pressure reduction 2, 3

Alternative Approaches

Instead of combining ACE inhibitors and ARBs, guidelines recommend:

1. Choose one RAAS blocker: Either an ACE inhibitor OR an ARB as the foundation of therapy, particularly for patients with:

   • Diabetes with albuminuria
   • Chronic kidney disease
   • Heart failure
   • High cardiovascular risk

2. Add complementary agents if blood pressure remains uncontrolled:

   • Dihydropyridine calcium channel blockers
   • Thiazide/thiazide-like diuretics
   • If additional RAAS blockade is needed, consider a mineralocorticoid receptor antagonist (spironolactone, eplerenone) 4

3. For resistant hypertension: Consider adding a mineralocorticoid receptor antagonist rather than combining ACE inhibitors and ARBs 1

Monitoring Recommendations

When using a single RAAS blocker (either ACE inhibitor OR ARB):

• Monitor serum creatinine/eGFR and potassium levels at initiation and at least annually
• Titrate to maximally tolerated doses for patients with albuminuria
• Be vigilant for side effects specific to each class (e.g., cough with ACE inhibitors)

Clinical Bottom Line

Despite theoretical advantages of dual RAAS blockade, the evidence clearly demonstrates that combining ACE inhibitors and ARBs increases harm without providing additional benefit for cardiovascular or renal outcomes. Clinicians should select either an ACE inhibitor OR an ARB based on patient-specific factors, but never use both simultaneously.