Lisinopril vs Losartan

An ACE inhibitor vs an ARB — both lower blood pressure through the renin-angiotensin system but at different points, producing similar efficacy with a key difference in side effects.

Overview

Lisinopril and losartan are both medications that lower blood pressure by interfering with the renin-angiotensin-aldosterone system (RAAS), one of the body's key hormonal systems for regulating blood pressure and fluid balance. Despite targeting the same system, they do so at different points in the cascade — lisinopril is an ACE inhibitor, while losartan is an angiotensin receptor blocker (ARB). Both are among the most prescribed medications in the United States, available as inexpensive generics, and supported by extensive clinical evidence.

They are frequently considered interchangeable for hypertension and related conditions, and the practical choice between them often comes down to a single, notable side effect difference. Understanding the mechanistic distinction helps explain why that side effect occurs with one but not the other.

How Each Works

The RAAS begins when the kidney releases renin in response to low blood pressure or low salt. Renin converts angiotensinogen (produced by the liver) to angiotensin I, which is then converted by angiotensin-converting enzyme (ACE) to angiotensin II. Angiotensin II is a potent vasoconstrictor — it narrows blood vessels, raises blood pressure, and stimulates aldosterone release (which causes the kidneys to retain sodium and water, further raising blood pressure).

Lisinopril blocks ACE — the enzyme that converts angiotensin I to angiotensin II. By doing so, it reduces the production of angiotensin II. However, ACE also breaks down bradykinin, a peptide that causes vasodilation. When ACE is inhibited by lisinopril, bradykinin levels rise. Elevated bradykinin in the respiratory tract causes the hallmark ACE inhibitor side effect: a persistent, dry, tickling cough that affects approximately 10–15% of patients (higher rates in certain populations).

Losartan does not affect the ACE enzyme at all. Instead, it directly blocks the angiotensin II receptor (specifically the AT1 subtype) — the receptor angiotensin II needs to bind to in order to cause vasoconstriction. Importantly, this means angiotensin II is still produced; it just cannot act on AT1 receptors. Because ACE is not inhibited, bradykinin is still metabolized normally, and the cough does not occur.

The Cough — The Key Clinical Difference

The ACE inhibitor cough is the most common reason physicians switch patients from lisinopril to losartan. It is not an allergic reaction but a pharmacological effect of bradykinin accumulation. The cough is dry, persistent, often described as a tickle or irritation in the throat, and does not resolve until the medication is stopped. It can begin weeks to months after starting the drug. Switching to an ARB like losartan typically resolves the cough within days to weeks.

Angioedema — a rare but potentially serious swelling of the face, lips, tongue, or throat — is another ACE inhibitor class effect linked to bradykinin. While rare (affecting less than 1% of users), it is a contraindication to further ACE inhibitor use. Losartan carries a much lower risk of angioedema, though it is not entirely zero.

Efficacy and Organ Protection

Both drug classes are considered roughly equivalent in their antihypertensive efficacy. Both are also recommended for patients with diabetes and chronic kidney disease because of their kidney-protective effects — they reduce intraglomerular pressure and slow the progression of diabetic nephropathy. The evidence base for ACE inhibitors in this context is somewhat older and more extensive, but ARBs have robust trial data as well (including the landmark RENAAL trial for losartan).

For heart failure and post-heart attack (myocardial infarction) protection, ACE inhibitors like lisinopril have historically been the standard first choice, with ARBs used as alternatives for those who cannot tolerate ACE inhibitors. Losartan has a specific FDA approval for reducing stroke risk in hypertensive patients with left ventricular hypertrophy.

Side Effects

Both classes share some side effects: elevated potassium (hyperkalemia) — because reducing angiotensin II activity means less aldosterone, causing the kidneys to retain potassium — and potential impacts on kidney function, particularly in patients with pre-existing kidney disease or those taking NSAIDs or diuretics. Blood pressure may drop significantly (hypotension), especially in volume-depleted patients. Both are contraindicated in pregnancy due to risks to the developing fetus.

Which Is Right for You?

For most patients with uncomplicated hypertension, either medication is a reasonable choice. Lisinopril is often chosen first given its lower cost and extensive evidence base. Losartan becomes the preferred option when a patient cannot tolerate the ACE cough, has a history of ACE inhibitor-related angioedema, or when certain co-existing conditions favor ARBs. Your doctor evaluates your full clinical picture — including kidney function, potassium levels, co-existing conditions, and medication history — to determine which is appropriate.

Frequently Asked Questions