No, ACE Inhibitors and ARBs Should Not Be Given Together
The simultaneous use of an ACE inhibitor and ARB is potentially harmful and is not recommended for treating hypertension or any other cardiovascular condition. 1
Why Combination Therapy Is Harmful
The combination of ACE inhibitors and ARBs significantly increases serious adverse events without providing additional clinical benefits:
Increased Risk of Adverse Events
Hyperkalemia risk is substantially elevated when both agents are used together, as both classes raise serum potassium levels through different mechanisms of renin-angiotensin system blockade 1, 2, 3
Acute kidney injury (AKI) occurs more frequently with dual therapy compared to either agent alone 1, 2, 3
Hypotension and syncope are more common with combination therapy 2, 3
Lack of Additional Clinical Benefits
The VA NEPHRON-D trial enrolled 1,448 patients with type 2 diabetes and found that combining losartan with lisinopril provided no additional benefit for the combined endpoint of GFR decline, end-stage renal disease, or death, but increased the incidence of hyperkalemia and acute kidney injury 2
The ONTARGET trial in high-risk vascular patients demonstrated that dual blockade increased harm without reducing cardiovascular events in any CKD subgroup, despite lowering proteinuria more than single agents 1
FDA drug labels explicitly warn against dual blockade of the renin-angiotensin system, stating that in most patients no benefit has been associated with using two RAS inhibitors concomitantly 2, 3
What About Proteinuria Reduction?
While combination therapy may reduce proteinuria more than single agents, this surrogate marker has not translated into improved clinical outcomes regarding mortality or progression to end-stage renal disease 1, 4
The reduction in albuminuria does not justify the increased risks of hyperkalemia and AKI 1
Guideline Consensus Across Organizations
Multiple major guidelines uniformly recommend against combination therapy:
ACC/AHA Hypertension Guideline (2017): Class III Harm recommendation with Level A evidence against simultaneous use 1, 4
KDOQI/KDIGO: Specifically notes the combination should be avoided to treat hypertension due to increased risks 1
Canadian Society of Nephrology: Recommends not using ACE inhibitors with ARBs in primary care 1, 4
American Diabetes Association: States the combined use should be avoided 4
What to Do Instead
For Hypertension Management
Use either an ACE inhibitor OR an ARB as monotherapy, not both 1, 4
If blood pressure remains uncontrolled, add a different class such as a calcium channel blocker or thiazide diuretic rather than combining ACE inhibitor with ARB 1, 4
For Proteinuric Kidney Disease
Optimize the dose of a single RAS blocker (either ACE inhibitor or ARB) to the maximum approved dose for hypertension treatment, rather than adding a second RAS blocker 1, 4
In stages 1-3 CKD with severely increased albuminuria, use either an ACE inhibitor or ARB as first-line therapy 1
If Patient Is Already on Dual Therapy
Transition to a single agent with close monitoring of blood pressure, renal function, and electrolytes 4
Monitor serum creatinine, estimated glomerular filtration rate, and potassium levels closely during the transition 4, 2, 3
Critical Monitoring Parameters
When using any single RAS blocker:
Check serum potassium and creatinine before initiation and within 1-2 weeks after starting therapy 2, 3
Monitor renal function periodically, especially in elderly patients, those on diuretics, or with compromised baseline renal function 2, 3
Avoid concomitant use with aliskiren (direct renin inhibitor) in patients with diabetes or GFR <60 mL/min, as this also constitutes harmful dual RAS blockade 2, 3
Common Clinical Pitfall
The most common error is assuming that "more blockade is better" for the renin-angiotensin system. Clinical trial evidence definitively shows this is not true - dual therapy increases harm without improving outcomes 1, 4, 2