Do Not Take Lisinopril and Losartan Together
You should not take lisinopril (an ACE inhibitor) and losartan (an ARB) at the same time—this combination is explicitly contraindicated by all major guidelines and the FDA drug label due to increased risks of kidney failure, stroke, and hyperkalemia without additional cardiovascular or renal benefits. 1, 2
Why This Combination Is Harmful
Evidence from Major Clinical Trials
The prohibition against combining ACE inhibitors with ARBs is based on strong evidence from two landmark trials:
ONTARGET trial: Demonstrated that dual blockade of the renin-angiotensin system with an ACE inhibitor plus ARB resulted in significantly increased rates of end-stage renal disease and stroke compared to monotherapy 1
VA NEPHRON-D trial: Specifically tested the combination of lisinopril plus losartan in diabetic patients with kidney disease and was stopped early because patients receiving both drugs experienced increased hyperkalemia and acute kidney injury without any additional benefit for preventing kidney disease progression or death 2
ALTITUDE trial: Confirmed these harms when testing dual renin-angiotensin system blockade, showing excess cases of end-stage renal disease and stroke 1
Specific Risks You Face
Hyperkalemia (dangerously high potassium): The combination dramatically increases your risk of life-threatening potassium elevations, particularly if you have diabetes or existing kidney disease 1, 3, 2
Acute kidney injury: Dual blockade causes more frequent and severe deterioration in kidney function compared to using either drug alone 3, 2
Hypotension and syncope: The combination causes excessive blood pressure lowering that can lead to dizziness, falls, and fainting 2
No added benefit: Despite these serious risks, the combination provides no improvement in cardiovascular outcomes or kidney disease progression beyond what a single agent achieves 3
What You Should Do Instead
Use Only One RAAS Blocker
Choose either lisinopril OR losartan—never both together. 1, 3
If you need better blood pressure control on a single agent, first optimize the dose of whichever drug you're taking (e.g., increase lisinopril up to 40 mg daily or losartan up to 100 mg daily) 4
Studies show that increasing the dose of a single ARB or ACE inhibitor is safer and nearly as effective as combining two RAAS blockers 4
Add Different Drug Classes for Better Control
If your blood pressure remains uncontrolled on an optimized dose of lisinopril or losartan, the preferred strategy is adding medications from different classes: 1, 3
- Calcium channel blockers (like amlodipine)—this is the most preferred combination 1
- Thiazide or thiazide-like diuretics (like chlorthalidone or hydrochlorothiazide) 1
- Loop diuretics if you have fluid retention 3
These combinations are proven safe and effective, unlike the ACE inhibitor + ARB combination.
Critical Warnings
If You're Already Taking Both
Stop one of these medications immediately and contact your prescribing physician. Do not stop both at once without medical guidance, as abrupt withdrawal can cause rebound hypertension. 2
Special High-Risk Situations
The combination is particularly dangerous if you have: 3, 2
- Chronic kidney disease (especially stage 4 with GFR <30 mL/min)
- Diabetes
- Heart failure
- Volume depletion or dehydration
Monitor Carefully If Switching
When transitioning from one RAAS blocker to another (not combining them), check your kidney function and potassium levels within 1-2 weeks 3
Why Some Doctors Might Have Considered This
Older research from the early 2000s suggested the combination might reduce proteinuria more than monotherapy 5, 6, 7, 4. However, subsequent large-scale trials definitively proved that any modest reduction in protein in the urine does not translate to better kidney or heart outcomes and comes at the cost of serious adverse events 1, 3, 2. This is outdated practice that has been abandoned based on current evidence.