Is Losartan Better Than Lisinopril? A Comparison

Neither losartan nor lisinopril is categorically better than the other for every patient. Both lower blood pressure to a similar degree, but they belong to different drug classes and diverge in side-effect profiles, tolerability, and some harder-to-see long-term outcomes. Losartan rarely causes cough and has a unique ability to lower uric acid, while lisinopril belongs to a class with stronger evidence for reducing overall mortality. Which one suits you depends on your health history, your tolerance for specific side effects, and what else is going on in your body besides high blood pressure.

How They Lower Blood Pressure Differently

Lisinopril is an ACE inhibitor. It blocks an enzyme that produces angiotensin II, a hormone that tightens blood vessels and tells the kidneys to hold onto salt. By shutting down that enzyme, lisinopril lets blood vessels relax and encourages the body to shed some sodium and water. A side effect of this blockade is that it also raises levels of bradykinin, a substance that widens blood vessels on its own but can irritate the airways.¹

Losartan is an angiotensin II receptor blocker, or ARB. Rather than preventing angiotensin II from being made, it blocks the receptor that angiotensin II plugs into. The end result on blood pressure is similar, but because losartan does not raise bradykinin levels, the cough and swelling issues that plague ACE inhibitors are far less common.

In head-to-head trials measuring actual blood pressure numbers, the two drugs perform about the same. One study of hypertensive patients found lisinopril lowered systolic pressure by about 20 points and diastolic by about 15, while losartan lowered systolic by about 17 and diastolic by about 12, with no statistically significant difference between them.² A separate randomized trial comparing losartan, lisinopril, and a calcium channel blocker found that roughly the same proportion of patients in each group hit their target blood pressure after 12 weeks.³ If your only goal is bringing the numbers down, either drug can do the job.

The Cough Problem

The most common reason people switch from lisinopril to losartan is a persistent, dry, hacking cough. It affects anywhere from 5% to 35% of people taking ACE inhibitors, depending on the population studied, and it is driven by that buildup of bradykinin in the lungs. It is annoying enough to make some patients stop their medication entirely.

Losartan largely avoids this. A double-blind trial specifically recruited elderly patients who had already developed a cough on an ACE inhibitor and then randomized them to losartan, lisinopril, or a diuretic. Cough came back in 97% of the lisinopril group but only 18% of the losartan group, a rate similar to the diuretic.⁴ Across ten separate comparative trials reviewed together, every single one reported less cough with ARBs than with ACE inhibitors.⁵ A pharmacovigilance analysis that excluded the first week of use (to filter out coincidental coughs) found that rates of cough were significantly higher for three different ACE inhibitors compared to losartan.⁶

A rarer but more dangerous cousin of the cough is angioedema, a sudden swelling of the face, lips, tongue, or throat that can threaten the airway. A large observational study tracking thousands of angioedema events found that the risk was highest with ACE inhibitors and much lower with ARBs, where it was roughly comparable to the risk seen with ordinary beta-blockers. Among ARBs, losartan had a slightly higher angioedema rate than other drugs in that class, though still far below ACE inhibitors.⁷ If you have ever experienced angioedema on lisinopril, the standard move is to switch to an ARB, though careful monitoring is still advised.

A Mortality Edge for ACE Inhibitors

Here is where the comparison gets uncomfortable for losartan advocates. A large meta-analysis pooling data from randomized trials involving nearly 160,000 patients examined whether drugs that target the renin-angiotensin system actually reduce the risk of dying. ACE inhibitors as a class showed a significant 10% reduction in all-cause mortality. ARBs, by contrast, showed no significant mortality benefit at all. The difference between the two classes was itself statistically significant.⁸

This does not necessarily mean losartan is dangerous or useless. The meta-analysis compared drug classes against various controls, not always directly against each other. And many of the ACE inhibitor trials studied patients with heart failure or post-heart-attack populations where ACE inhibitors have decades of outcome data. Still, the finding matters. If all else is equal and you tolerate both drugs without problems, ACE inhibitors carry a stronger track record for keeping people alive. That is one reason lisinopril and similar drugs remain first-line choices in many treatment guidelines, with ARBs positioned as alternatives when ACE inhibitors are not tolerated.

Losartan’s Unique Effect on Uric Acid

Losartan has a property that no other ARB and no ACE inhibitor shares: it lowers uric acid. High uric acid can lead to gout, a painful form of arthritis, and is also linked to kidney stones and cardiovascular risk. Losartan promotes uric acid excretion through the kidneys, acting as a mild uricosuric agent. A review of all available studies found that losartan consistently produced statistically significant reductions in uric acid levels, while no other ARB reached that benchmark.⁹

Clinical guidelines now recommend adding or switching to losartan for hypertensive patients who also have gout, specifically because of this uric acid benefit.¹⁰ One study found that uric acid dropped from about 7.0 to 5.9 mg/dL in hypertensive patients given losartan, regardless of whether they took a lower or higher dose.¹¹ If you have both high blood pressure and elevated uric acid, this is a real, practical reason to prefer losartan over lisinopril.

Kidney Protection in Diabetes

Both drugs are used to protect the kidneys in people with diabetes, because blocking the renin-angiotensin system reduces the pressure inside the kidney’s filtering units and slows the leak of protein into the urine. A year-long trial comparing losartan to enalapril (an ACE inhibitor closely related to lisinopril) in people with type 2 diabetes and early kidney disease found that both drugs significantly reduced the amount of albumin leaking into the urine, and both stabilized the rate at which the kidneys’ filtering capacity was declining. There was no difference between the two.¹²

The practical takeaway is straightforward: for protecting kidneys in diabetes, the two classes appear interchangeable. The choice between them comes down to side effects and individual patient factors rather than one drug’s superiority at preserving kidney function.

Potassium and Kidney Function Risks

Both losartan and lisinopril can raise potassium levels, because blocking the renin-angiotensin system reduces aldosterone, which normally helps the kidneys flush potassium out. For most people with healthy kidneys, this is a minor and manageable effect. But in people whose kidney function is already reduced, the risk gets more meaningful.

A study looking at patients with lower kidney filtration rates found that lisinopril raised potassium by about 0.28 mEq/L on average, while the ARB tested (valsartan, which works similarly to losartan) raised it by about 0.12 mEq/L, roughly 43% less.¹³ That difference may matter in someone already teetering near the upper limit of safe potassium levels. If your doctor monitors your potassium closely because of kidney disease, this is a point in losartan’s favor, though potassium monitoring is standard practice with either drug class.

Stroke Prevention and Heart Remodeling

The LIFE trial is the single most cited study in losartan’s favor for hard cardiovascular outcomes. It enrolled patients with high blood pressure and thickening of the heart’s main pumping chamber, then compared losartan-based treatment to atenolol-based treatment (a beta-blocker) over several years. Losartan outperformed atenolol on a composite of cardiovascular death, stroke, and heart attack. The stroke results were particularly striking: a 40% reduction in any stroke, a 70% reduction in fatal stroke, and a 45% reduction in the type of stroke caused by blood clots blocking brain arteries.¹⁴

Among patients in LIFE with isolated systolic hypertension and heart thickening, losartan reduced cardiovascular mortality by roughly half and total mortality by about 28% compared to atenolol. Losartan also reduced the incidence of new-onset diabetes.¹⁵ A separate analysis from the same trial confirmed that losartan reversed the thickening of the heart wall more effectively than atenolol, even after accounting for how much each drug lowered blood pressure.¹⁶

These are impressive results, but an important caveat applies: LIFE compared losartan to a beta-blocker, not to an ACE inhibitor. You cannot conclude from this trial that losartan beats lisinopril for stroke prevention. What you can conclude is that losartan has strong evidence against at least one comparator for reducing strokes and reversing heart thickening in high-risk patients. Head-to-head outcome trials between losartan and lisinopril specifically are thin on the ground, which is why the comparison often relies on class-level data and indirect reasoning.

Heart Failure and Cardiomyopathy

In heart failure, ACE inhibitors have historically been the standard of care, with ARBs reserved for patients who cannot tolerate them. A randomized, double-blind trial tested lisinopril against losartan in patients with cardiomyopathy related to Duchenne muscular dystrophy. Both groups started with similar heart function, and after a year both showed a significant and nearly identical improvement in ejection fraction, climbing from about 47.5% to roughly 55%. There was no difference between the two drugs.¹⁷

This was a small, disease-specific trial, so it does not settle the broader question. But it aligns with the general pattern: when you measure what the drugs do to heart structure and function directly, they tend to look equivalent. The mortality advantage seen with ACE inhibitors in the meta-analysis described earlier may reflect mechanisms beyond simple blood-pressure or heart-function effects, or it may reflect the fact that ACE inhibitors have simply been studied in more and larger outcome trials.

Why Race Can Affect the Choice

Drug response varies by ancestry, and this is one area where the data have real clinical implications. Several monotherapy trials have shown that Black patients tend to have a smaller blood-pressure response to both ACE inhibitors and ARBs compared to white patients, though this difference largely disappears when either drug is combined with a diuretic.¹⁸

A more surprising finding came out of the LIFE trial. While losartan beat atenolol in the overall study population, the opposite was true for Black participants: in that subgroup, atenolol-treated patients actually fared better on the primary composite outcome of cardiovascular death, stroke, and heart attack.¹⁹ This interaction was statistically significant, and it has influenced treatment guidelines that recommend thiazide diuretics or calcium channel blockers as preferred first-line agents for Black patients with hypertension, rather than ACE inhibitors or ARBs as monotherapy.²⁰ When ACE inhibitors or ARBs are used in this population, they are typically paired with a diuretic.

Dosing and How Long People Stick With Treatment

Both lisinopril and losartan are typically taken once a day, but their blood-pressure coverage across a full 24-hour period is not identical. At the time of their FDA approvals, the agency evaluated how well each drug’s effect lasted from one dose to the next. Losartan’s trough-to-peak ratio was about 70%, meaning the drug still had 70% of its peak effect right before the next dose. Lisinopril’s ratio ranged more widely, from 30% to 70%.²¹ For some patients on lisinopril, blood pressure may creep up toward the end of the dosing interval, which is why some clinicians prescribe it twice daily.

Adherence also favors ARBs. A large retrospective study of over 7,000 patients starting blood pressure medication for the first time found that persistence with treatment was highest among people prescribed an ARB, and progressively lower with ACE inhibitors, beta-blockers, calcium channel blockers, and diuretics. The better tolerability of ARBs, especially the absence of cough, likely drives this pattern. A drug that works perfectly in theory does nothing for you if you stop taking it because of side effects.

Why You Should Never Take Both Together

It might seem logical that hitting the renin-angiotensin system from two angles at once would offer extra protection, but trials have consistently shown that combining an ACE inhibitor with an ARB does more harm than good. Adding lisinopril to losartan in patients with type 2 diabetes and protein in the urine increased the rates of dangerously high potassium and acute kidney injury without delivering better outcomes.²² A separate randomized trial found no trend suggesting that dual therapy with an ACE inhibitor and an ARB improved survival or kidney outcomes compared to either drug alone in patients with albumin in the urine and diabetes or other cardiovascular risk factors.²³ Current guidelines are unambiguous: pick one or the other, not both.

Cost and Practical Prescribing

Both lisinopril and losartan are available as inexpensive generics, and for most patients in the United States either drug costs only a few dollars a month. That said, a systematic review of cost-effectiveness analyses found that ARBs as a class were generally more cost-effective than ACE inhibitors when quality-adjusted life years were factored in, largely because their better tolerability meant fewer medication switches, fewer office visits for cough complaints, and better adherence over time. The actual drug price difference is negligible in the generic era; the cost savings come from downstream healthcare use.

If you are prescribed lisinopril and tolerate it well, there is no cost-based reason to switch. If you develop a cough and your doctor moves you to losartan, you will not pay more, and you may save money overall by avoiding the cycle of complaints, dose adjustments, and follow-up appointments that an intolerable medication creates.

When Each Drug Has the Edge

Rather than a single winner, the comparison shakes out to a set of clinical scenarios where one drug makes more sense than the other:

Cough or angioedema history: Losartan is the clear choice. Lisinopril will almost certainly bring the cough back, and angioedema risk is meaningfully higher with ACE inhibitors.
Gout or high uric acid: Losartan’s uricosuric effect is unique and guideline-supported. Lisinopril does nothing for uric acid.
Post-heart-attack or heart failure: Lisinopril and other ACE inhibitors have the deeper evidence base for reducing mortality. Losartan is a reasonable backup if ACE inhibitors are not tolerated.
Left ventricular thickening: Losartan has strong evidence from the LIFE trial for reversing heart wall thickening and reducing stroke risk in this population.
Reduced kidney function with borderline potassium: ARBs may cause a smaller potassium rise, giving losartan a slight safety advantage, though monitoring is essential with either drug.

Your doctor’s choice between these two drugs is rarely arbitrary. It reflects a weighing of your specific medical history, your tolerance for side effects, what other medications you take, and which outcomes matter most in your situation. If you are doing well on one, switching to the other for its own sake is unlikely to help and might introduce problems you did not have before.