Is a combination of an Angiotensin-Converting Enzyme (ACE) inhibitor and an Angiotensin Receptor Blocker (ARB) recommended as a first-line treatment?

Combination of ACE Inhibitor and ARB is Not Recommended as First-Line Treatment

The combination of an ACE inhibitor and an ARB is not recommended for the treatment of hypertension due to increased risks of hyperkalemia and acute kidney injury without additional cardiovascular benefits. 1, 2

First-Line Treatment Options for Hypertension

The recommended first-line agents for hypertension include:

• ACE inhibitors OR ARBs (not both together)
• Thiazide/thiazide-like diuretics
• Calcium channel blockers (CCBs)

These recommendations are consistent across major guidelines 1, 2. For patients with specific comorbidities, the choice of first-line agent may be tailored:

• For patients with albuminuria or CKD: ACE inhibitor OR ARB is preferred 1
• For patients with established coronary artery disease: ACE inhibitor OR ARB is recommended 1

Evidence Against ACE Inhibitor + ARB Combination

Multiple guidelines and drug labels explicitly warn against dual RAAS blockade:

1. Increased adverse effects without additional benefits:

   • The FDA drug labels for both lisinopril and losartan specifically warn against dual blockade 3, 4
   • The VA NEPHRON-D trial showed no additional benefit but increased hyperkalemia and acute kidney injury when combining lisinopril with losartan 3

2. Specific risks of combination therapy include:

   • Hyperkalemia (4.8-24.5 times higher odds compared to monotherapy) 2, 5
   • Acute kidney injury 1, 3
   • Hypotension 5
   • Increased medication discontinuation due to adverse effects (RR 1.38,95% CI 1.22-1.55) 5

Appropriate Use of RAAS Blockers

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

• Titrate to maximally tolerated doses for patients with albuminuria 2
• Monitor serum creatinine/eGFR and potassium levels at least annually 1
• For patients requiring multiple antihypertensive medications, preferred combinations include:
  • RAAS blocker + dihydropyridine CCB
  • RAAS blocker + thiazide/thiazide-like diuretic 2

Alternative to Dual RAAS Blockade

If additional RAAS blockade is needed beyond an ACE inhibitor or ARB monotherapy:

• Consider adding a mineralocorticoid receptor antagonist (such as spironolactone or eplerenone) instead of combining ACE inhibitor and ARB 2
• Monitor potassium levels closely when using mineralocorticoid receptor antagonists

Special Considerations

For patients with diabetes and kidney disease:

• ACE inhibitors or ARBs are particularly beneficial for preventing progression of kidney disease 1
• Even in this high-risk population, the combination of ACE inhibitor and ARB is not recommended due to increased risk of adverse events 1

In summary, while both ACE inhibitors and ARBs are effective first-line agents for hypertension, their combination should be avoided due to increased risks without additional benefits. Instead, if blood pressure remains uncontrolled on monotherapy, adding a CCB or thiazide diuretic is the preferred approach.