Risks and Recommendations for ACE Inhibitors and ARBs

Introduction to Risks

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, 2

Dual blockade of the renin-angiotensin system with both an ACE inhibitor and ARB significantly increases the risk of hyperkalemia and acute kidney injury compared to using either agent alone 1, 2
Clinical trials including ONTARGET and VA NEPHRON-D have demonstrated increased harm from combination treatment 1

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 2, 3
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

The European Society of Cardiology guidelines explicitly state that the addition of an ARB to the combination of an ACE inhibitor and a mineralocorticoid antagonist is not recommended due to the risk of renal dysfunction and hyperkalaemia 4, 5
The Canadian Society of Nephrology recommends not using ACE inhibitors with ARBs in primary care 1, 6
The American Diabetes Association states that the combined use of ACE inhibitors and ARBs should be avoided 7, 8
The American College of Cardiology/American Heart Association 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 9, 10

In patients with albuminuria or proteinuria, either an ACE inhibitor or ARB alone is recommended as first-line therapy 7, 3
For patients with hypertension and chronic kidney disease, either an ACE inhibitor or ARB should be used, but not both together 10

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 rather than adding a second agent 2
For resistant hypertension, consider adding other classes of antihypertensive medications rather than combining ACE inhibitors and ARBs 9
Monitor serum creatinine, estimated glomerular filtration rate, and potassium levels at least annually in patients taking either an ACE inhibitor or ARB 2