Lisinopril: Independent Evidence on Cough, Pregnancy & Funding

Table of contents

• Evidence summary
• What lisinopril is
• How it works
• What it is prescribed for
• What works and what does not
• Benefits by claim
• Risks and all side effects
• All interactions
• Who should avoid lisinopril
• Dosage and how to take it
• Follow the money: who makes it and who funded the evidence
• Related research
• Frequently asked questions
• Sources and funding notes

Evidence summary

Independent evidence and credibility scorecard

Independence tiers: 1 = regulator, government body or publicly funded research with no commercial stake; 2 = academic or Cochrane team with no declared commercial funding for the work; 3 = independent authors analysing mostly manufacturer-run trials, or minor declared industry ties; 4 = manufacturer-funded or manufacturer-authored. Credibility runs from A (highest) to D.

Eight of the thirteen sources are from the United States or the United Kingdom, so the verdict reflects Anglo-American practice. Two of the thirteen were paid for by makers, and both are labelled as such throughout.

What lisinopril is

Lisinopril is an angiotensin-converting enzyme (ACE) inhibitor taken by mouth. It is excreted unchanged in the urine and is not metabolised by the liver (FDA label, section 12.3).

• Brand names: Zestril (Prinivil was a second brand, but a DailyMed search finds no current label for it). A lisinopril oral solution (Qbrelis) and a lisinopril and hydrochlorothiazide tablet (Zestoretic) also exist (openFDA query).
• Generics: The same FDA database lists 16 generic (ANDA) applications (openFDA query). Most prescriptions today are for the generic.
• Perindopril: A second ACE inhibitor, sold under the brand Coversyl and as generics. It is licensed in Europe for hypertension, symptomatic heart failure and risk reduction in stable coronary artery disease (Coversyl SmPC, Irish copy, 2010).
• Prescription status: Prescription-only. Both drugs are in the ACE-inhibitor class that NICE names in its hypertension guideline (NICE NG136).

How it works

ACE converts angiotensin I into angiotensin II, which narrows blood vessels and triggers aldosterone release. Lisinopril blocks that step, so blood vessels relax and aldosterone falls (FDA label, section 12.1). The label says the benefits in hypertension and heart failure appear to result mainly from suppressing this system. The fall in aldosterone can raise potassium slightly: in one label study the mean rise was about 0.1 mEq/L, but about 15% of patients rose by more than 0.5 mEq/L.

That is the proven human mechanism. The label does not explain cough. The usual explanation, that ACE inhibitors also reduce the breakdown of bradykinin, is not stated on the labels we read, so we do not rely on it.

What it is prescribed for

• High blood pressure in adults and in children aged 6 years and over (FDA label, section 1).
• Heart failure as add-on treatment, and the first six weeks after a heart attack (same label).
• Renal complications of diabetes in hypertensive people with type 2 diabetes and early kidney disease, among the harmonised European indications for Zestril (EMA referral).
• Perindopril adds stable coronary artery disease (SmPC 4.1).

What works and what does not

Benefits by claim

Is lisinopril a good first-choice blood-pressure drug?

It depends on who you are. ALLHAT, the largest publicly funded trial, found lisinopril equal to chlorthalidone for heart attacks and coronary deaths but behind it on heart failure and stroke (ALLHAT). The Cochrane update of 45 trials found overall survival the same across drug classes, with differences in individual outcomes (Chen 2018). NICE offers an ACE inhibitor or an ARB first to people with type 2 diabetes, or under 55 and not of Black African or African-Caribbean family origin. It suggests an ARB in preference for people of Black African or African-Caribbean family origin, and a calcium-channel blocker for most others aged 55 or over (NICE NG136 1.4.30 to 1.4.35). See our guide to blood-pressure medicines and hypertension.

Lisinopril versus ARBs such as losartan

Head-to-head trials of at least one year found no difference in death or cardiovascular events (Li 2014). The practical difference is tolerability: about 1.8 percentage points fewer people stopped an ARB, an absolute gain that means treating about 55 people for 4 years to spare one a stop. The Cochrane authors stress that ARBs have not been tested against placebo for blood pressure, so the ACE inhibitor case rests on older evidence (Li 2014). See losartan and ramipril.

Heart failure

This is where ACE inhibitors have their clearest survival benefit. Across placebo-controlled trials the odds of death fell by about a quarter (OR 0.77, 95% CI 0.67 to 0.88), and of death or hospital admission by about a third (OR 0.65) (Garg and Yusuf). The label's ATLAS trial (over 3,000 patients) found that 35 mg was at least as good as 2.5 mg of lisinopril (FDA label, section 14.2). See heart failure with reduced ejection fraction.

After a heart attack

In GISSI-3, six weeks of lisinopril cut six-week death from 7.2% to 6.4% (FDA label, section 14.3). The label says the longer-term heart-failure result could not be interpreted because the trial was unblinded and many patients stayed on the drug.

Kidney protection

The Cochrane review in diabetic kidney disease found that ACE inhibitors may prevent kidney failure (RR 0.61) but the evidence is low certainty and risk of bias is high (Natale 2024). An older Cochrane review in people with diabetes and normal urine albumin found ACE inhibitors reduced new albuminuria (RR 0.71, 0.56 to 0.89) and death (RR 0.84, 0.73 to 0.97); some of its authors declared industry speaker fees and grants, including from Servier (Lv 2012). See chronic kidney disease and the heart.

Perindopril

EUROPA, run by the maker, found a 20% relative reduction in cardiovascular events over 4.2 years in people with stable coronary disease and no heart failure, with about 50 people treated for 4 years to prevent one event (EUROPA). The PROGRESS trial found a 28% lower stroke risk (95% CI 17 to 38) with a perindopril-based regimen after stroke, but the benefit came mainly from adding indapamide: perindopril alone produced no discernible reduction (PROGRESS). We did not retrieve PROGRESS's funding statement.

Risks and all side effects

Common side effects

In hypertension trials, 5.7% stopped because of adverse reactions. Events at least 2 percentage points more frequent than with placebo were headache (3.8%), dizziness (3.5%) and cough (2.5%). In heart failure the extra events were low blood pressure (3.8%) and chest pain (2.1%) (FDA label, 6.1).

How kidney function and potassium should be monitored

For adults with CKD, NICE says to measure potassium and eGFR before starting an ACE inhibitor or ARB, and repeat both 1 to 2 weeks after starting and after each dose increase. It says not to modify the dose if eGFR falls by less than 25% or creatinine rises by less than 30% from baseline, and to look for other causes such as dehydration or NSAIDs if the change is larger. It advises against starting if potassium is above 5.0 mmol/litre (NICE NG203 1.6.15 to 1.6.23). The label says to monitor renal function and potassium "periodically" in all patients (FDA label). In advanced CKD (eGFR below 30), stopping the drug did not clearly slow kidney decline (STOP-ACEi), so a stop decision belongs to the kidney team.

All interactions

Perindopril carries the same interaction warnings, including lithium and potassium-sparing diuretics (SmPC 4.4 and 4.5). For herbal and supplement overlaps see supplements and heart medicines.

Who should avoid lisinopril

• Pregnancy and planned pregnancy: boxed warning; stop as soon as pregnancy is detected (FDA label). A Tennessee cohort found first-trimester exposure alone carried a risk ratio of 2.71 for major malformations, and concluded it "cannot be considered safe" (Cooper 2006). The perindopril SmPC advises switching to a safer alternative before planned pregnancy (SmPC 4.4). See heart disease during pregnancy.
• Breastfeeding: there are no data on lisinopril in human milk; the Zestril label advises not to breastfeed during treatment (FDA label, 8.2).
• Any previous angioedema on an ACE inhibitor, hereditary or idiopathic angioedema, and anyone allergic to the drug (FDA label, 4).
• People of Black African or African-Caribbean family origin with hypertension: NICE suggests considering an ARB in preference (NICE NG136 1.4.30). The label also notes a smaller average blood-pressure response to ACE-inhibitor monotherapy in Black patients.
• Kidney disease or renal artery narrowing: closer monitoring, and a halved starting dose if creatinine clearance is 10 to 30 mL/min (FDA label, 2.4).
• Children under 6, or with GFR below 30 mL/min/1.73 m²: safety and effectiveness not established (FDA label, 8.4).
• Surgery: the drug may block compensatory renin release during anaesthesia, causing low blood pressure; the perindopril SmPC advises stopping it one day before surgery (SmPC 4.4).

Dosage and how to take it

These are label doses, not personal advice. Your dose is set by your prescriber.

• Hypertension (adults): label starting dose 10 mg once daily; usual range 20 to 40 mg a day in a single dose. "Doses up to 80 mg have been used but do not appear to give greater effect" (FDA label, 2.1).
• Children 6 and over: label starting dose 0.07 mg per kg (up to 5 mg) once daily (same section).
• Heart failure: label starting dose 5 mg once daily, raised as tolerated to a maximum of 40 mg (FDA label, 2.2).
• Acute heart attack: 5 mg within 24 hours of symptoms, 5 mg after 24 hours, 10 mg after 48 hours, then 10 mg daily for at least six weeks (FDA label, 2.3).
• Food: does not alter absorption. Absorption is about 25%, with large variation between people (FDA label, 12.3).
• Perindopril (arginine salt): the Irish copy of the UK-sourced SmPC gives a hypertension starting dose of 5 mg once daily in the morning (2.5 mg if the renin-angiotensin system is strongly activated), rising to 10 mg after a month. For stable coronary disease it is 5 mg for two weeks, then 10 mg (SmPC 4.2). Perindopril salts are not dose-equivalent: the 5 mg arginine tablet contains 3.395 mg of perindopril.

Follow the money: who makes it and who funded the evidence

Who made it, and who sells it now

• Lisinopril's origin: we could not open a primary source on who first developed it. The only trace we could check is a 2001 trade-press headline that refers to "Merck/AstraZeneca lisinopril exclusivity", which points to Merck and AstraZeneca as the originator companies, as the brands Prinivil and Zestril suggest (Pink Sheet 2001). The article is behind a paywall and we saw the headline only.
• US brand today: openFDA lists Zestril under NDA 019777 with sponsor TWI Pharmaceuticals, Zestoretic under Almatica and Qbrelis under Azurity (openFDA). The Zestril label we used is distributed by Upsher-Smith of Maple Grove, Minnesota (DailyMed). A DailyMed search for "Prinivil" returned no current labels (DailyMed query).
• Generics: 16 generic applications are listed with the FDA (openFDA). In England, we found lisinopril accounted for 7.6 million prescription items and about £8.0 million in actual cost in the 12 months to June 2025, or roughly £1.05 per item. Ramipril was 35.4 million items at about £1.03 per item, and perindopril erbumine 3.5 million items at about £2.94 per item (NHSBSA English Prescribing Data; our sums across 12 monthly files, July 2024 to June 2025).
• Perindopril's maker: Servier, a French company (European Commission). The Commission called perindopril a blockbuster and "used to be Servier's best-selling product".

Documented integrity event: the perindopril generic-delay case

On 9 July 2014 the European Commission fined Servier and five generic makers a total of €427.7 million. It found that Servier bought the most advanced non-patented production technology in 2004 and then settled patent challenges with generic rivals between 2005 and 2007, with payments of "several tens of millions of euros" to keep them out of the market. Servier's own fine was €330,997,200, and the generic firms were Niche/Unichem, Matrix (now part of Mylan), Teva, Krka and Lupin (European Commission press release). The Commission said that in 2007 generic perindopril prices in the UK dropped on average by 90% from Servier's previous price level once the last legal challenger won. The decision concerns competition and prices. It says nothing about perindopril's safety or the accuracy of its trials. It was appealed, and we did not verify the final court outcome. We found no comparable antitrust action involving lisinopril.

Who funded the evidence

• Publicly funded: ALLHAT (NHLBI), STOP-ACEi (NIHR and MRC), the Cooper and Toh safety studies (US federal agencies) and NICE (UK Department of Health and Social Care).
• Maker-funded: ONTARGET (Boehringer Ingelheim, which sells the competing ARB telmisartan) and EUROPA (Servier). Both are well-conducted placebo or active-controlled trials, but readers should know who paid. The ONTARGET result, equal outcomes with more side effects on the combination, did not favour the sponsor's own drug.
• Cochrane reviews: the 2014 and 2018 reviews reported no author conflicts. The 2024 diabetic kidney review lists one author with consultancy ties to AstraZeneca, Vifor, Eli Lilly and Boehringer Ingelheim, and the 2012 review lists industry speaker fees and grants, including from Servier, for some authors (Natale 2024; Lv 2012). Cochrane states it is independent of commercial interests (Cochrane).
• Why little new trial money: lisinopril is a cheap generic, so no company has a strong reason to fund new head-to-head trials. The core efficacy data are old.

Related research

For wider, evidence-graded context, see these Pure City Research guides:

• Ramipril: uses, kidney monitoring, cough and safety
• Chronic cough: causes, drugs and funding
• Losartan: uses, potassium, monitoring and pregnancy safety
• Blood-pressure medicines
• Hypertension
• Amlodipine
• Home blood-pressure monitoring
• Chronic kidney disease and the heart
• Heart failure with reduced ejection fraction
• Heart disease during pregnancy
• Supplements and heart medicines
• Lithium (interacts with lisinopril)

Frequently asked questions

Sources and funding notes

What we could not verify: the funding sections of the Cochrane reviews (we saw author declarations only); the ALLHAT paper's full-text funding statement and any manufacturer drug donations; the GISSI-3 paper (we relied on the FDA label's summary); the PROGRESS funding statement; the current UK lisinopril SmPC (the perindopril SmPC we used is a 2010 Irish copy); the original developer of lisinopril (only a paywalled 2001 trade headline names Merck and AstraZeneca); the final court outcome of the Servier appeals; and any lisinopril-specific NHS prescribing narrative beyond our own sums of the NHSBSA open data. The cough mechanism is not stated on the labels we read, so we do not state one as fact.

1. Zestril (lisinopril) FDA-approved label, DailyMed, revised 11/2024 — regulator label; distributed by Upsher-Smith; efficacy data from company programmes.
2. NICE NG136, hypertension in adults (updated 26 February 2026) — guideline; UK public body.
3. NICE NG203, chronic kidney disease — guideline; UK public body.
4. ALLHAT, JAMA 2002 — randomised trial; NHLBI (registry).
5. ONTARGET, NEJM 2008 — randomised trial; Boehringer Ingelheim (registry).
6. Chen et al., Cochrane 2018, first-line RAS inhibitors versus other classes — systematic review; funding not retrieved; no author conflicts.
7. Li et al., Cochrane 2014, ACE inhibitors versus ARBs — systematic review; funding not retrieved; no conflicts.
8. Garg and Yusuf, JAMA 1995 — meta-analysis in heart failure; no funding statement in the PubMed record.
9. Natale et al., Cochrane 2024, diabetic kidney disease — systematic review; one author with industry consultancies.
10. Lv et al., Cochrane 2012, preventing diabetic kidney disease — systematic review; some authors with industry fees and grants.
11. Bhandari et al., STOP-ACEi, NEJM 2022 — randomised trial; NIHR and MRC (UK).
12. Hu et al., J Clin Hypertens 2023, ACE-inhibitor cough — network meta-analysis; no conflicts; funding not stated.
13. Toh et al., Arch Intern Med 2012, angioedema — cohort study; FDA Mini-Sentinel.
14. Cooper et al., NEJM 2006, first-trimester exposure — cohort study; AHRQ and a Public Health Service contract.
15. Fu et al. 2021, malformations meta-analysis — funding not stated in the record.
16. EUROPA, Lancet 2003 — randomised trial; Servier (ISRCTN).
17. PROGRESS, Lancet 2001 — randomised trial; funding statement not retrieved.
18. Coversyl Arginine 5 mg SmPC, Irish Medicines Board copy, 2010 — regulator-approved; marketed by Servier.
19. EMA referral for Zestril — EU regulator; harmonised indications (CHMP opinion September 2003).
20. NHSBSA English Prescribing Data — NHS arm's-length body; our totals for July 2024 to June 2025.
21. European Commission press release IP/14/799, 9 July 2014 — competition regulator.
22. openFDA Drugs@FDA query for lisinopril NDAs — US government data, unvalidated per its disclaimer.

Educational research reviewed 6 October 2026. This article is not medical advice; talk to a qualified clinician or pharmacist before starting, stopping or combining treatments.