Why shouldn't you take an Angiotensin Receptor Blocker (ARB) and an Angiotensin-Converting Enzyme inhibitor (ACE) together?

Why You Should Not Take an ACE Inhibitor and ARB Together

The combination of ACE inhibitors and ARBs should be avoided due to increased risk of adverse events such as hyperkalemia and acute kidney injury (AKI) without providing additional clinical benefits beyond single-agent therapy. 1

Risks of Combination Therapy

• Dual blockade of the renin-angiotensin system with both an ACE inhibitor and ARB significantly increases the risk of hyperkalemia (elevated potassium levels) and acute kidney injury compared to using either agent alone 1
• Clinical trials including ONTARGET (Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial) and VA NEPHRON-D (Veterans Affairs Nephropathy in Diabetes) have demonstrated increased harm from combination treatment 1
• The combination therapy leads to higher rates of medication discontinuation due to adverse effects in patients with heart failure (RR, 1.38 [95% CI, 1.22-1.55]) and in patients with acute myocardial infarction with left ventricular dysfunction (RR, 1.17 [95% CI, 1.03-1.34]) 2
• Symptomatic hypotension occurs more frequently with dual therapy compared to single-agent therapy 2

Lack of Additional Benefits

• Despite the theoretical advantage that combination therapy might provide more complete blockade of the renin-angiotensin system, clinical trials have not demonstrated improved cardiovascular or renal outcomes with dual therapy 1
• While the combination may lower proteinuria more than single agents, this has not translated to improved clinical outcomes in terms of mortality or progression to end-stage renal disease 1
• Two major clinical trials studying the combinations of ACE inhibitors and ARBs found no benefits on cardiovascular disease or chronic kidney disease outcomes 1

Guideline Recommendations

• The European Society of Cardiology (ESC) guidelines explicitly state that "the addition of an ARB (or renin inhibitor) to the combination of an ACE inhibitor AND a mineralocorticoid antagonist is NOT recommended because of the risk of renal dysfunction and hyperkalaemia" 1
• The Canadian Society of Nephrology recommends "not using ACE inhibitors with ARBs in primary care" 1
• The American Diabetes Association states that "the combined use of ACE inhibitors and ARBs should be avoided" 1
• The ACC/AHA hypertension guideline states that "simultaneous use of an ACE inhibitor, ARB, and/or renin inhibitor is potentially harmful and is not recommended to treat adults with hypertension" 1

Appropriate Use of Single Agents

• Both ACE inhibitors and ARBs are effective as monotherapy for hypertension, heart failure, and diabetic nephropathy 3, 4
• For patients who cannot tolerate ACE inhibitors (commonly due to cough), ARBs provide an effective alternative with similar clinical benefits but fewer adverse effects 3, 4
• In patients with albuminuria or proteinuria, either an ACE inhibitor or ARB alone is recommended as first-line therapy 1
• For patients with hypertension and chronic kidney disease, either an ACE inhibitor or ARB should be used, but not both together 1

Clinical Implications

• If a patient is already on dual therapy with both an ACE inhibitor and ARB, consider transitioning to a single agent with close monitoring 1
• When maximum blockade of the renin-angiotensin system is desired, optimize the dose of a single agent (either ACE inhibitor or ARB) rather than adding a second agent 1
• For resistant hypertension, consider adding other classes of antihypertensive medications (such as thiazide diuretics, calcium channel blockers, or mineralocorticoid receptor antagonists) rather than combining ACE inhibitors and ARBs 1
• Monitor serum creatinine, estimated glomerular filtration rate, and potassium levels at least annually in patients taking either an ACE inhibitor or ARB 1