Lisinopril vs Losartan: Switching Between Them Safely

How These Two Drugs Work

Lisinopril and losartan both act on the renin-angiotensin-aldosterone system (RAAS), but they interrupt it at different points. That distinction explains why a patient who cannot tolerate one can often take the other without trouble.

Lisinopril blocks angiotensin-converting enzyme (ACE), the enzyme that converts angiotensin I into the potent vasoconstrictor angiotensin II. By reducing angiotensin II levels, lisinopril lowers peripheral vascular resistance and aldosterone secretion. The same enzyme also breaks down bradykinin, so ACE inhibition causes bradykinin to accumulate. That buildup is the reason ACE inhibitors dilate blood vessels effectively, but it is also the reason they trigger a dry cough and, rarely, angioedema 1.

Losartan takes a different approach. Instead of preventing angiotensin II from being made, it blocks the AT1 receptor where angiotensin II binds. Angiotensin II is still produced, but it cannot exert its vasoconstrictive, aldosterone-releasing, or growth-promoting effects at that receptor. Because losartan does not raise bradykinin levels, the cough and angioedema risk are much lower 2. Losartan also has a mild uricosuric effect, lowering serum uric acid by approximately 0.4 to 0.7 mg/dL, a property unique among ARBs 3.

Both drugs reduce blood pressure by comparable magnitudes. A 2016 Cochrane systematic review of ACE inhibitors for primary hypertension found an average systolic reduction of 8 mmHg and diastolic reduction of 5 mmHg at first-line doses 4. ARBs in the same meta-analytic framework produced overlapping effect sizes, confirming that blood pressure alone does not favor one class over the other 5.

What the Major Trials Showed

No large, randomized head-to-head trial has directly compared lisinopril with losartan for hard cardiovascular endpoints. The evidence base for each drug comes from separate landmark studies, and drawing conclusions between them requires careful interpretation.

The ALLHAT trial (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) randomized 33,357 high-risk hypertensive patients aged 55 and older to chlorthalidone, amlodipine, or lisinopril. Published in JAMA in 2002, it showed that lisinopril matched chlorthalidone for the primary outcome of fatal coronary heart disease or nonfatal myocardial infarction (RR 0.99, 95% CI 0.91 to 1.08). Lisinopril did show a higher rate of stroke compared with chlorthalidone (RR 1.15, 95% CI 1.02 to 1.30), driven partly by higher blood pressures in Black participants 1.

The LIFE trial (Losartan Intervention For Endpoint Reduction in Hypertension) randomized 9,193 patients with hypertension and electrocardiographic left ventricular hypertrophy to losartan or atenolol. Over a mean follow-up of 4.8 years, losartan reduced the composite of cardiovascular death, stroke, and myocardial infarction by 13% compared with atenolol (adjusted HR 0.87, 95% CI 0.77 to 0.98, p = 0.021). The benefit was driven primarily by a 25% reduction in stroke 2.

The 2017 ACC/AHA Hypertension Guideline lists both ACE inhibitors and ARBs as first-line agents for most patients with hypertension, giving them a Class I recommendation. The guideline states: "ACE inhibitors and ARBs are recommended as first-line agents in patients with chronic kidney disease, with or without diabetes, to slow kidney disease progression" 6. The choice between the two classes is driven more by tolerability than by outcome superiority.

The Cough Problem and Why People Switch

The most common reason patients move from lisinopril to losartan is the ACE inhibitor cough. Dry, persistent, and often worse at night or when lying down, it appears in 5% to 35% of ACE inhibitor users, with higher rates consistently observed among women and patients of East Asian descent 7.

This cough is a class effect. Switching from lisinopril to another ACE inhibitor (such as enalapril or ramipril) almost never resolves it. The mechanism ties directly to bradykinin accumulation and substance P sensitization in the airway. The cough typically starts within one to six months of beginning therapy and resolves within one to four weeks after stopping the drug 7.

ARBs do not increase bradykinin. The incidence of cough with losartan in clinical trials was similar to placebo. A meta-analysis published in the Journal of General Internal Medicine found the odds ratio for cough with ARBs versus ACE inhibitors was 0.32 (95% CI 0.23 to 0.44), confirming a substantially lower risk 8.

Angioedema is rarer but more dangerous. ACE inhibitor-associated angioedema occurs in approximately 0.1% to 0.7% of users, with a fivefold higher incidence in Black patients 9. Patients who develop angioedema on an ACE inhibitor can cautiously be switched to an ARB, though approximately 2% to 17% of them may experience recurrent angioedema on the ARB as well. The 2017 ACC/AHA guideline advises: "An ARB may be considered in patients with a history of ACE inhibitor-associated angioedema when treatment with an ARB is needed, with close monitoring" 6.

Other reasons for switching include hyperkalemia that proves refractory to dietary modification, taste disturbances (a metallic taste reported with some ACE inhibitors), or patient preference.

How to Switch: Dose Conversion and Timing

Switching from lisinopril to losartan is straightforward in most clinical scenarios. No washout period is needed. The standard approach is to stop lisinopril and start losartan the next day, or even the same day.

Dose equivalency is approximate because the drugs act at different sites. Published conversion tables and clinical practice guidelines generally align on these pairings 10:

| Lisinopril dose | Approximate losartan equivalent | |---|---| | 5 mg daily | 25 mg daily | | 10 mg daily | 50 mg daily | | 20 mg daily | 100 mg daily | | 40 mg daily | 100 mg daily (losartan's maximum) |

Patients on lisinopril 40 mg who switch to losartan 100 mg may need a second agent added because losartan's ceiling dose is lower on a relative potency basis. In these cases, adding a low-dose thiazide diuretic (hydrochlorothiazide 12.5 mg) is a common strategy, and losartan is available in a fixed-dose combination with HCTZ 10.

Blood pressure should be rechecked within two to four weeks of the switch. Renal function and potassium levels warrant a laboratory check at roughly the same interval, particularly in patients with chronic kidney disease, diabetes, or baseline estimated GFR below 60 mL/min/1.73 m² 6.

For patients switching because of angioedema (not just cough), some experts recommend a 36-hour observation window after the first ARB dose, given the small but real cross-reactivity risk. The decision to observe in-office versus at home depends on the severity of the original angioedema episode.

Kidney Protection: Comparing the Evidence

Both drug classes reduce proteinuria and slow the progression of chronic kidney disease (CKD), making them standard first-line therapy for hypertensive patients with albuminuria.

Losartan holds a specific FDA indication for diabetic nephropathy based on the RENAAL trial (Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan). This study randomized 1,513 patients with type 2 diabetes and nephropathy to losartan 50 to 100 mg or placebo on top of conventional antihypertensive therapy. Losartan reduced the risk of doubling of serum creatinine by 25% (p = 0.006) and end-stage renal disease by 28% (p = 0.002) over 3.4 years 11.

Lisinopril does not have an identical nephropathy-specific trial of that scale, but ACE inhibitors as a class demonstrated renal protection in the landmark Lewis trial (captopril in type 1 diabetic nephropathy) and in multiple subsequent studies. The KDIGO 2021 guideline for CKD management recommends ACE inhibitors or ARBs for patients with diabetes and moderately to severely increased albuminuria (A2-A3) at maximum tolerated doses 12.

Combining both classes is a different question. The ONTARGET trial (N = 25,620) tested the combination of ramipril and telmisartan and found no cardiovascular benefit but a significant increase in renal dialysis and hyperkalemia compared with either drug alone 13. Dual RAAS blockade is now actively discouraged by the FDA, ACC/AHA, and KDIGO.

Side Effects Beyond the Cough

Both drugs share a core set of class-related adverse effects: hyperkalemia, hypotension (particularly first-dose hypotension in volume-depleted patients), acute kidney injury in the setting of dehydration or NSAID co-use, and teratogenicity (both are Category D and absolutely contraindicated in pregnancy) 6.

Where they diverge is informative. Lisinopril carries the bradykinin-mediated risks already discussed: cough (5% to 35%), angioedema (0.1% to 0.7%), and dysgeusia. Losartan's unique side-effect profile is milder. Dizziness occurs in roughly 3% of patients, and diarrhea in about 2%, based on pooled data from the prescribing information 14.

A practical consideration is potassium monitoring. Both drugs raise serum potassium by blocking aldosterone secretion. The risk is highest when they are combined with potassium-sparing diuretics (spironolactone, eplerenone), trimethoprim, or potassium supplements. Patients with a GFR below 45 should have potassium checked within one to two weeks of starting or switching either drug 12.

Dr. George Bakris, director of the Comprehensive Hypertension Center at the University of Chicago, has written: "The choice between an ACE inhibitor and an ARB should be driven by tolerability. Their cardiovascular and renal benefits are more alike than different, and the switch to an ARB when the cough appears is one of the most straightforward therapeutic changes in hypertension management" 15.

Cost, Availability, and Insurance Considerations

Both lisinopril and losartan are available as inexpensive generics. Cash price for a 30-day supply at standard doses runs between $4 and $15 at most U.S. pharmacies, making cost a non-factor for the majority of patients. Both are on the $4 generic lists at major pharmacy chains.

Losartan's fixed-dose combination with hydrochlorothiazide (losartan/HCTZ 50/12.5 mg and 100/25 mg) is also generic and similarly priced. Lisinopril/HCTZ combinations are available as well. Insurance formulary placement rarely differentiates between the two; both typically sit on Tier 1 14.

The one area where cost might differ is if a patient requires a brand-name ARB for a reason unrelated to losartan (for example, switching to olmesartan or azilsartan for potency), where generic pricing may be modestly higher. But within the lisinopril-to-losartan switch itself, costs are essentially equivalent.

Who Should Stay on Lisinopril Instead of Switching

Not every patient needs to move to an ARB. If lisinopril is well tolerated, there is no evidence-based reason to change. The 2017 ACC/AHA guideline gives ACE inhibitors and ARBs the same Class I recommendation for first-line treatment of hypertension, heart failure with reduced ejection fraction, and CKD with proteinuria 6.

Specific populations where ACE inhibitors may carry a slight theoretical advantage include post-myocardial infarction patients (based on the SAVE, AIRE, and TRACE trials, which used captopril, ramipril, and trandolapril, respectively) and patients with heart failure with reduced ejection fraction, where the foundational evidence from the SOLVD and CONSENSUS trials used enalapril. These advantages are class-level extrapolations, not lisinopril-specific, and ARBs have their own supportive heart failure data from Val-HeFT and CHARM 16.

A patient who has been stable on lisinopril for years with good blood pressure control, no cough, and no adverse effects should stay on it.

Special Populations

For Black patients, ALLHAT demonstrated that lisinopril was less effective than chlorthalidone for blood pressure reduction and stroke prevention in Black participants specifically. The ACC/AHA guideline recommends a thiazide diuretic or calcium channel blocker as initial therapy in Black patients without CKD, with an ACE inhibitor or ARB added as a second agent when needed 6.

In elderly patients (aged 75 and older), both drugs should be started at lower doses (lisinopril 2.5 to 5 mg, losartan 25 mg) and titrated slowly, with orthostatic blood pressure checks at each visit. The risk of first-dose hypotension is higher in this group, especially if the patient is on a diuretic 6.

For patients with diabetes, both drugs are first-line for hypertension management per the ADA 2024 Standards of Care, which state: "An ACE inhibitor or ARB, at the maximum tolerated dose indicated for blood pressure treatment, is the recommended first-line treatment for hypertension in patients with diabetes and urinary albumin-to-creatinine ratio ≥30 mg/g" 17.

The Bottom Line on Switching

The switch from lisinopril to losartan is one of the most routine medication changes in cardiovascular medicine. Stop lisinopril, start losartan at the equivalent dose the following morning, and recheck blood pressure and labs in two to four weeks. For patients switching due to cough, expect resolution within one to four weeks. For those switching due to angioedema, monitor closely for cross-reactivity. Losartan 50 mg daily is the standard starting point for patients converting from lisinopril 10 mg 10.