Irbesartan and Lisinopril Should Not Be Used Together
Simultaneous use of an ACE inhibitor (lisinopril) and an ARB (irbesartan) is potentially harmful and is not recommended for treating hypertension. 1
Rationale Against Dual RAS Blockade
Dual blockade of the renin-angiotensin system (RAS) with an ARB and ACE inhibitor is associated with increased risks of adverse events compared to monotherapy: 2, 3
- Hyperkalemia (elevated potassium levels)
- Hypotension (dangerously low blood pressure)
- Acute renal failure/impaired kidney function
- No additional benefit in most patients compared to single agent therapy
The 2017 ACC/AHA hypertension guidelines explicitly state that simultaneous use of an ACE inhibitor, ARB, and/or renin inhibitor is potentially harmful (Class III: Harm; Level of Evidence: A) 1
Clinical trials have shown an increase in adverse events with combination therapy despite potential reductions in proteinuria 1, 4
Individual Uses of These Medications
Lisinopril (ACE Inhibitor)
- Effective first-line agent for hypertension 1
- Usual dosage range: 10-40 mg once daily 1
- Do not use in combination with ARBs or direct renin inhibitors 1
Irbesartan (ARB)
- Effective alternative for hypertension, especially in patients who cannot tolerate ACE inhibitors 5, 6
- Usual dosage range: 150-300 mg once daily 1
- Provides 24-hour blood pressure control with once-daily dosing 7, 8
- Has demonstrated renoprotective effects in diabetic nephropathy 5, 6
Appropriate Alternative Approaches
Use either an ACE inhibitor OR an ARB as monotherapy, not both together 1
If blood pressure control is inadequate with a single agent at maximum dose, consider adding:
For patients who cannot tolerate ACE inhibitors due to cough or angioedema, ARBs are the recommended alternative 1
Monitoring Recommendations
- When using either medication alone, monitor:
Special Considerations
Patients with diabetes are at particularly high risk of adverse events with dual RAS blockade 1, 2, 3
The FDA has issued specific contraindications against using aliskiren (direct renin inhibitor) with either ACE inhibitors or ARBs in patients with diabetes or renal impairment 1
Patients with bilateral renal artery stenosis are at increased risk of acute renal failure with either ACE inhibitors or ARBs 1
Conclusion
The evidence clearly demonstrates that combining irbesartan and lisinopril is not recommended due to increased risk of adverse events without additional clinical benefit. Either agent alone is effective for hypertension management, but they should not be used together.