Lisinopril vs Losartan: Switching Between Them Safely

Lisinopril (brand names Zestril and Prinivil) is an angiotensin-converting enzyme (ACE) inhibitor. Losartan (brand name Cozaar) is an angiotensin II receptor blocker (ARB). Both are oral tablets used for hypertension, and both act on the renin-angiotensin-aldosterone system, but they interrupt it at different steps, which is why a patient who cannot tolerate one can often take the other without difficulty.

The switch from lisinopril to losartan is one of the most routine medication changes in primary care, and it is driven almost entirely by tolerability, not by a documented outcome advantage. No large randomized trial has directly compared lisinopril against losartan head-to-head for heart attack, stroke, or death. Both drugs carry a Class I recommendation from the 2017 ACC/AHA hypertension guideline for first-line treatment of hypertension, and clinicians generally switch directly from one to the other, with no washout period required. The most common reason to switch is the dry cough associated with ACE inhibitors, a class effect tied to bradykinin buildup that ARBs do not share.

What is established, what is plausible, and what is not established

Established: Lisinopril and losartan both lower blood pressure and both reduce proteinuria in patients with albuminuric kidney disease. ACE inhibitors cause a dry cough in a meaningful minority of users through a bradykinin-mediated mechanism; ARBs do not share this mechanism and cause cough at rates close to placebo. Combining an ACE inhibitor with an ARB (dual RAAS blockade) is discouraged because trial evidence in this drug class showed increased kidney injury and hyperkalemia without a cardiovascular benefit.

Plausible but not rigorously quantified on this page: The precise magnitude of blood pressure reduction, exact cough incidence, and exact trial hazard ratios reported in older secondary summaries of ALLHAT, LIFE, RENAAL, and ONTARGET are widely cited in cardiology literature, but the specific figures should be checked against the original trial publications before being used in patient counseling or clinical documentation. This draft intentionally avoids repeating exact confidence intervals and percentages that could not be verified against a confirmed primary source during this review.

Not established: Whether losartan produces superior hard cardiovascular outcomes compared with lisinopril specifically. The trials most often cited for each drug (ALLHAT for lisinopril, LIFE for losartan) tested different comparators (chlorthalidone/amlodipine and atenolol, respectively) in different populations, so their results cannot be stacked to declare one drug the winner over the other.

How the two drugs work

Lisinopril blocks the enzyme that converts angiotensin I into angiotensin II. Less angiotensin II means less vasoconstriction and less aldosterone release. The same enzyme that converts angiotensin I also breaks down bradykinin, so ACE inhibition allows bradykinin to accumulate. That accumulation contributes to the vasodilating effect of ACE inhibitors, and it is also the mechanism behind the characteristic dry cough and, rarely, angioedema.

Losartan works downstream of that step. It blocks the AT1 receptor that angiotensin II binds to, so angiotensin II is still produced but cannot act at that receptor. Because losartan does not affect bradykinin metabolism, it does not carry the same cough or angioedema risk. Losartan also has a mild uric-acid-lowering effect that is not shared by other ARBs, which can be relevant for patients who also have gout, though the size of that effect requires confirmation in the primary literature before it is used to guide a specific patient's regimen.

What the landmark trials showed, and why they cannot be stacked against each other

The evidence for lisinopril's cardiovascular effects comes largely from ALLHAT, a large trial that randomized high-risk hypertensive patients aged 55 and older to chlorthalidone, amlodipine, or lisinopril and compared rates of fatal coronary disease, nonfatal heart attack, and stroke. The evidence most often cited for losartan comes from the LIFE trial, which compared losartan with atenolol in patients who had hypertension and electrocardiographic left ventricular hypertrophy, tracking a composite of cardiovascular death, stroke, and heart attack.

These are two separate trials, in two different populations, against two different comparator drugs (a diuretic/calcium channel blocker on one side, a beta-blocker on the other). Neither trial tells you what would happen if lisinopril and losartan were tested directly against each other. The reasonable clinical conclusion, and the one reflected in guideline recommendations, is that both drug classes are appropriate first-line options for most patients with hypertension, and the trial data support using either one rather than favoring one over the other on outcomes alone.

The 2017 ACC/AHA hypertension guideline lists ACE inhibitors and ARBs as first-line, Class I options for most patients with hypertension, including those with chronic kidney disease, with or without diabetes. The guideline's emphasis is on individualizing choice around tolerability and comorbidities rather than declaring superiority of one class.

The cough problem, and why it drives most switches

The most common reason a patient moves from lisinopril to losartan is the ACE inhibitor cough: dry, persistent, often worse at night or when lying flat. It is a recognized class effect of ACE inhibitors tied to bradykinin accumulation and airway sensitization, and switching to a different ACE inhibitor (enalapril, ramipril, and so on) rarely fixes it, because the mechanism is shared across the class. The cough generally develops within the first months of therapy and improves over one to several weeks after the drug is stopped, though the exact timeline varies between patients.

ARBs, including losartan, do not raise bradykinin levels, and cough rates with ARBs in clinical trials have been reported as close to placebo. This is the single strongest, most reproducible reason clinicians switch a coughing patient from an ACE inhibitor to an ARB rather than to a different ACE inhibitor.

Angioedema is rarer and more serious than cough. It involves swelling of the lips, tongue, throat, or face and can affect breathing. Angioedema, or any sudden swelling of the face, lips, tongue, or throat, or difficulty breathing or swallowing, is a medical emergency and requires immediate emergency care, not a routine follow-up appointment. Patients who develop angioedema on an ACE inhibitor are sometimes cautiously switched to an ARB under close medical supervision, because a minority of patients with ACE inhibitor angioedema will also react to an ARB. This decision should be individualized by the prescribing clinician, not made by the patient alone.

Other reasons clinicians switch include hyperkalemia that does not respond to dietary changes, a metallic taste some patients report on ACE inhibitors, or straightforward patient preference once the mechanism is explained.

How the switch is usually done

In most cases, no washout period is used. The typical approach is to stop lisinopril and start losartan the next dose, sometimes the same day. Dose equivalence is approximate, because the two drugs act at different points in the same pathway, and published conversion guidance generally clusters around the following pairings. These figures are commonly cited in clinical dosing references and should be confirmed against current prescribing information and the patient's renal function and blood pressure response, since individual titration always takes priority over a fixed table.

Because losartan's maximum labeled dose is lower on a relative-potency basis than lisinopril 40 mg, a patient switching from the higher lisinopril dose may need a second blood-pressure agent added, commonly a low-dose thiazide diuretic, and losartan is available as a fixed-dose combination with hydrochlorothiazide.

After any switch, blood pressure should be rechecked within a few weeks, and kidney function and potassium should be checked around the same time, especially in patients with chronic kidney disease, diabetes, or reduced kidney function at baseline. For patients switching specifically because of angioedema rather than cough, some clinicians use a period of direct observation after the first ARB dose given the small risk of cross-reactivity; the length and setting of that observation should be decided by the prescriber based on how severe the original reaction was.

Decision framework: which drug fits which situation

This is not a ranking of one drug over the other. It is a map of the specific clinical circumstances that should change the decision, built from the evidence and guideline positions described above. It does not replace an individualized recommendation from the prescribing clinician.

Kidney protection: what each drug's evidence actually supports

Both classes reduce proteinuria and are recommended first-line for hypertensive patients with albuminuria. Losartan carries an FDA-recognized indication specifically for diabetic nephropathy, based on a large placebo-controlled trial in patients with type 2 diabetes and existing nephropathy that reported a reduced risk of doubling of serum creatinine and progression to end-stage kidney disease. Lisinopril does not have an identically scaled nephropathy-specific outcome trial, but ACE inhibitors as a class have renal-protective evidence from other studies, and current KDIGO guidance for chronic kidney disease recommends an ACE inhibitor or an ARB, not a preference for one over the other, in patients with diabetes and significant albuminuria at the maximum tolerated dose.

Combining the two classes is a separate and settled question. A large outcomes trial testing combined ACE inhibitor and ARB therapy found no cardiovascular benefit over either drug alone, with more kidney injury, hyperkalemia, and low blood pressure episodes in the combination arm. Dual RAAS blockade with an ACE inhibitor plus an ARB is discouraged by regulators and by cardiology and nephrology guidelines.

Side effects beyond the cough

Both drugs share a core set of class effects: hyperkalemia, low blood pressure (particularly with the first dose in volume-depleted patients), acute kidney injury during dehydration or with concurrent NSAID use, and harm to a developing fetus, which makes both classes contraindicated in pregnancy.

Where the two diverge is informative for the switching decision. Lisinopril carries the bradykinin-related risks already discussed: cough and, rarely, angioedema. According to losartan's FDA-approved prescribing information, dizziness and diarrhea are among the more commonly reported side effects in clinical trials, at rates in the low single digits, without the cough or angioedema signal seen with ACE inhibitors (FDA label, Cozaar).

Potassium monitoring matters for both drugs, since both reduce aldosterone secretion. The risk rises when either is combined with potassium-sparing diuretics, trimethoprim, or potassium supplements, and patients with reduced kidney function should have potassium checked within one to two weeks of starting or switching either drug.

Cost and access

Both lisinopril and losartan are widely available as low-cost generics, commonly available for a modest monthly cash price at major U.S. pharmacy chains as of this writing; exact pricing varies by pharmacy, insurance formulary, and region, and should be confirmed at the point of purchase since generic drug pricing changes over time. Fixed-dose combinations with hydrochlorothiazide exist for both drugs and are similarly priced as generics. For the specific switch discussed on this page, cost is rarely the deciding factor.

Who should stay on lisinopril rather than switch

A patient who is well controlled on lisinopril, without cough, without angioedema, and without another compelling reason to change, does not need to switch. The 2017 ACC/AHA guideline gives ACE inhibitors and ARBs the same first-line status for hypertension, heart failure with reduced ejection fraction, and CKD with proteinuria. Some of the foundational heart failure trial evidence (for example, the trials underlying ACE inhibitor use after a heart attack and in reduced ejection fraction heart failure) used other ACE inhibitors rather than lisinopril specifically, and ARBs have their own supportive heart failure trial evidence, so neither class should be treated as universally superior for these indications.

Special populations

Black patients: outcome data comparing an ACE inhibitor against a thiazide diuretic have shown less benefit for blood pressure and stroke prevention with the ACE inhibitor in this population specifically. Guidelines generally recommend a thiazide diuretic or calcium channel blocker as initial therapy in Black patients without CKD, adding an ACE inhibitor or ARB as a second agent when needed.

Older adults (75 and older): both drugs should generally be started at lower doses and titrated slowly, with orthostatic blood pressure checks, because the risk of first-dose low blood pressure is higher in this group, especially when combined with a diuretic.

Diabetes with albuminuria: current diabetes care guidelines recommend an ACE inhibitor or an ARB, at the maximum tolerated dose for blood pressure control, as first-line therapy in patients with diabetes and a meaningfully elevated urinary albumin-to-creatinine ratio. Neither class is preferred over the other by these guidelines; the choice again comes down to tolerability.

The bottom line on switching

Moving from lisinopril to losartan is a routine, generally low-risk change when it is done for the right reason, most often the ACE inhibitor cough. The typical approach is to stop lisinopril and start losartan at an approximately equivalent dose without a washout period, then recheck blood pressure and basic labs within a few weeks. Patients switching because of cough can generally expect improvement over the following weeks. Patients switching because of angioedema need closer, clinician-directed monitoring because of a real, if uncommon, cross-reactivity risk. This page describes general patterns; the specific dose, timing, and monitoring plan for any individual patient should come from their prescribing clinician.