Dual Therapy with Lisinopril and Losartan Is Not Recommended
Combining lisinopril (an ACE inhibitor) and losartan (an ARB) is not recommended due to increased risk of adverse effects without additional cardiovascular benefit. 1, 2
Why This Combination Should Be Avoided
Dual blockade of the renin-angiotensin system (RAS) with both an ACE inhibitor and ARB increases risks of hyperkalemia, syncope, acute kidney injury, and other adverse events without providing additional cardiovascular benefits 1, 2
The Veterans Affairs Nephropathy in Diabetes (VA NEPHRON-D) trial showed that therapy with both losartan and lisinopril increased the risk of acute kidney injury and hyperkalemia, with no benefit for mortality or cardiovascular events compared to losartan alone 1, 2
The ONTARGET trial reported no improvement in cardiovascular events in patients treated with both telmisartan (an ARB) and ramipril (an ACE inhibitor) compared to either agent alone, while increasing the risk of serum creatinine doubling and hyperkalemia 1
Multiple major guidelines explicitly state that combining ACE inhibitors and ARBs is contraindicated or not recommended:
- The 2024 ESC Guidelines state: "Combining two RAS blockers (ACE inhibitor and an ARB) is not recommended" 1
- The 2024 American Diabetes Association standards of care note: "The use of both ACE inhibitors and ARBs in combination is contraindicated given the lack of added ASCVD benefit and increased rate of adverse events" 1
Preferred Approach to Hypertension Management
First-line antihypertensive medications include ACE inhibitors, ARBs, thiazide-like diuretics, and dihydropyridine calcium channel blockers 1
When a single agent is insufficient for blood pressure control, the preferred approach is to combine medications with complementary mechanisms of action 1:
- ACE inhibitor + calcium channel blocker
- ACE inhibitor + thiazide diuretic
- ARB + calcium channel blocker
- ARB + thiazide diuretic
If two drugs are insufficient, a three-drug combination is recommended, typically a RAS blocker (either ACE inhibitor OR ARB) with a dihydropyridine calcium channel blocker and a thiazide/thiazide-like diuretic 1
Special Considerations
In patients with albuminuria or diabetic nephropathy, either an ACE inhibitor OR an ARB (not both) is recommended as first-line therapy due to their renoprotective effects 1
For patients who cannot tolerate ACE inhibitors (e.g., due to cough or angioedema), ARBs are an appropriate alternative with similar efficacy 1
Beta-blockers can be added to either an ACE inhibitor or ARB when there are specific indications such as coronary artery disease, post-myocardial infarction, heart failure with reduced ejection fraction, or for heart rate control 1
Monitoring Recommendations
When using either an ACE inhibitor OR an ARB (not both together), monitor:
- Renal function and serum electrolytes within 1-2 weeks after initiation
- Renal function and electrolytes after dose changes
- Regular monitoring during maintenance therapy 1
Be particularly vigilant in patients with reduced renal function, diabetes, or those taking potassium supplements or potassium-sparing diuretics 1
Bottom Line
Lisinopril and losartan should not be taken together. Choose either one or the other as part of your antihypertensive regimen, and if blood pressure control is inadequate, add a medication from a different class such as a calcium channel blocker or thiazide diuretic rather than combining these two RAS blockers.