Can a patient with a history of hypertension or heart failure take lisinopril (Angiotensin-Converting Enzyme inhibitor) and irbesartan (Angiotensin II Receptor Blocker) together?

No, Lisinopril and Irbesartan Should Not Be Taken Together

Combining lisinopril (an ACE inhibitor) and irbesartan (an ARB) is explicitly contraindicated and not recommended by all major guidelines and FDA labeling. This combination increases serious risks without providing additional therapeutic benefit.

Why This Combination Is Contraindicated

Guideline Consensus Against Dual RAS Blockade

• All major hypertension guidelines unanimously advise against combining an ACE inhibitor with an ARB 1.
• The 2024 ESC Guidelines explicitly state: "Combining two RAS blockers (ACE inhibitor and an ARB) is not recommended" 1.
• The 2014 international guidelines review confirms this is "the only drug combination that is advised against by all guidelines" 1.

FDA Drug Label Warnings

• The FDA label for lisinopril warns that "dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy" 2.
• The irbesartan FDA label contains identical warnings about dual RAS blockade 3.
• Both labels state: "In most patients no benefit has been associated with using two RAS inhibitors concomitantly" and recommend to "in general, avoid combined use of RAS inhibitors" 2, 3.

Specific Risks of This Combination

Increased Adverse Events Without Benefit

• Combining lisinopril and irbesartan increases the risk of hypotension (dangerously low blood pressure) 4, 2, 3.
• Hyperkalemia (elevated potassium levels) risk is significantly increased, which can cause life-threatening cardiac arrhythmias 2, 3.
• Acute renal failure and progressive renal dysfunction are more common with dual RAS blockade 4, 2, 3.

Evidence from Clinical Trials

• The ONTARGET trial demonstrated that combining an ACE inhibitor with an ARB resulted in excess cases of end-stage renal disease compared to monotherapy 1.
• The ALTITUDE trial was prematurely terminated due to excess cases of end-stage renal disease and stroke when dual RAS blockade was used 1.
• No additional therapeutic benefit is gained from combining two RAS blockers compared to optimal dosing of a single agent 4.

What to Do Instead

Optimize Single Agent Therapy First

• If blood pressure is inadequately controlled on one RAS blocker, optimize the dose of that single agent before considering additional medications 4.
• For lisinopril: titrate up to maximum doses (up to 40mg daily for hypertension, up to 35mg daily for heart failure) 5.
• For irbesartan: optimize to 150-300mg daily 4, 6, 7.

Add Medications from Different Classes

• The preferred approach is to combine a single RAS blocker (either lisinopril OR irbesartan, not both) with a calcium channel blocker or thiazide diuretic 1, 4.
• The 2024 ESC Guidelines recommend: "Preferred combinations are a RAS blocker (either an ACE inhibitor or an ARB) with a dihydropyridine CCB or diuretic" 1.
• For three-drug therapy, use a RAS blocker + calcium channel blocker + thiazide diuretic 1.

For Resistant Hypertension

• Consider adding an aldosterone antagonist (spironolactone) rather than a second RAS blocker 4.
• This approach provides additional blood pressure reduction without the risks of dual RAS blockade 4.

Clinical Monitoring If Patient Is Already on Both

If a patient presents already taking both medications:

• Discontinue one of the two agents immediately (typically continue whichever was started first or better tolerated).
• Monitor serum creatinine and potassium within 2-4 weeks after discontinuing one agent 8.
• Check blood pressure closely to ensure adequate control remains with monotherapy, adding agents from different classes if needed 4.
• Watch for signs of hyperkalemia (muscle weakness, palpitations, ECG changes) during the transition period 2, 3.

Special Considerations

Heart Failure Context

• Even in heart failure, where RAS blockade is beneficial, dual ACE inhibitor/ARB therapy is not recommended 1.
• The VAL-HeFT trial showed no mortality benefit from adding an ARB to an ACE inhibitor in heart failure patients 1.
• A single optimally-dosed RAS blocker combined with beta-blockers, diuretics, and mineralocorticoid receptor antagonists is the evidence-based approach 1.