Enalapril
Enalapril maleate (angiotensin-converting enzyme inhibitor)
Written by Aaron CuhaReviewed Sep 2026
Also known as: Vasotec, Enalapril maleate, Enalaprilat (active metabolite), MK-421
Did not extend mouse lifespan by the Interventions Testing Program's protocol test; a 2024 reanalysis found a 7 percent male median gain by the Gehan test, which weights early deaths. In people it is a blood pressure and heart failure drug with one of the deepest mortality records in cardiology, none of it about ageing.
Overview
Enalapril is an ACE inhibitor approved in the 1980s for hypertension and heart failure and still prescribed by the tens of millions as a generic. It is on this site because the NIA Interventions Testing Program tested it, and because the longevity community cites that test as a positive. The record needs stating carefully.
In people, enalapril's evidence is about heart failure mortality, not lifespan in the healthy. CONSENSUS randomised 253 patients with the most severe heart failure (NYHA class IV) and found six-month mortality of 26 percent on enalapril against 44 percent on placebo, a 40 percent relative reduction (p = 0.002), all of it in deaths from progressive pump failure and none in sudden death; hypotension forced withdrawal in 7 enalapril patients and none on placebo. SOLVD Treatment randomised 2,569 patients with symptomatic heart failure and ejection fraction of 0.35 or less: over a mean 41.4 months, 35.2 percent died on enalapril against 39.7 percent on placebo, a 16 percent risk reduction (95 percent CI 5 to 26, p = 0.0036). SOLVD Prevention randomised 4,228 people with the same low ejection fraction but no symptoms: total mortality was not significantly reduced (8 percent, 95 percent CI -8 to 21, p = 0.30), while the combined endpoint of death or development of heart failure fell 29 percent (p < 0.001). In other words the drug's mortality benefit is real and confined to people whose hearts are already failing; the trial in people without symptoms found no significant mortality effect.
In mice, the Interventions Testing Program fed enalapril at 120 ppm from 4 months of age. Male median lifespan rose 7 percent, which was not significant by the protocol log-rank test (p = 0.22), and females showed nothing; the ITP reported it as a null. In 2024 a reanalysis of all ITP data with the Gehan test, which weights deaths by how many animals remain alive and so is sensitive to early and midlife mortality, found the male effect significant (p = 0.046), and noted that the survival curves violated the proportional hazards assumption the log-rank test relies on. The same reanalysis says the benefit of enalapril, like captopril, is "markedly diminished with advancing age".
Enalapril is an approved prescription drug in every jurisdiction this site covers; generic tablets and an oral solution are marketed in the US.
Mechanism of action
Enalapril is a prodrug hydrolysed in the liver to enalaprilat, which inhibits angiotensin-converting enzyme, lowering angiotensin II and aldosterone and raising bradykinin. In people this lowers blood pressure, reduces afterload, and in heart failure slows the progressive dilatation of the left ventricle, which is the mechanism the SOLVD investigators credited for the mortality benefit. It also carries the class effects of cough, hyperkalaemia, first-dose hypotension and, rarely, angioedema. In mice, the ITP selected it as one of several drugs acting on the renin-angiotensin system, following reports that ACE inhibition extends rodent lifespan. Captopril, tested later at 180 ppm, produced a small significant female gain. Whether the male-only Gehan signal for enalapril reflects blood pressure, kidney protection or something else was not examined; the reanalysis itself describes a midlife effect that fades in old age.
Human evidence
Extensive for heart failure and hypertension, none for ageing. Enalapril has been randomised against placebo in thousands of people with heart disease and has been prescribed for forty years, so its efficacy in heart failure and its side effect profile are among the best characterised of any drug on this site. No trial has tested it for any ageing endpoint in healthy people.
- CONSENSUS, 253 patients with severe (class IV) heart failure: six-month mortality 26 versus 44 percent, a 40 percent relative reduction, all in progressive heart failure deaths.
- SOLVD Treatment, 2,569 patients with symptomatic heart failure: mortality 35.2 versus 39.7 percent over 3.4 years, a 16 percent relative reduction.
- SOLVD Prevention, 4,228 people with low ejection fraction but no symptoms: mortality reduction 8 percent with a confidence interval spanning zero (p = 0.30); development of heart failure reduced 29 percent.
- Side effects across the trials: first-dose hypotension, cough, raised potassium and creatinine, and angioedema as a rare class effect; in CONSENSUS hypotension forced withdrawal in 7 of 127 on drug and none on placebo.
- No trial has given enalapril to people without cardiovascular disease to see whether they live longer.
What this does not tell you: Every mortality benefit here was measured in people whose hearts were failing, and the one trial in people without symptoms found no significant mortality effect. These data say nothing about whether a normotensive adult taking enalapril would live longer, and the mouse signal that prompts the question is a reanalysis result in males only that the reanalysis authors themselves describe as fading with age.
Reading the research record
The NIA Interventions Testing Program runs each compound in parallel at three sites (The Jackson Laboratory, the University of Michigan and UT Health San Antonio) in genetically heterogeneous UM-HET3 mice, tests both sexes, analyses them separately, pools the sites in a site-stratified log-rank test, and publishes every result whether or not the compound worked. It is publicly funded by the National Institute on Aging with no pharmaceutical sponsorship. Enalapril was fed at 120 ppm from 4 months and reported as a null: a 7 percent male median gain that did not reach significance by log-rank (p = 0.22), and nothing in females.
"Gehan-only" needs explaining because it is a weaker and more specific claim than "extended lifespan". The ITP's protocol test is the log-rank test, which weights every death equally and is most sensitive when a treatment lowers mortality by a constant proportion across the whole lifespan. In 2024 a group at UT Health San Antonio reanalysed all ITP survival data from 2004 to 2022, 132 compound by sex comparisons, with the Gehan test, which weights deaths by how many animals are still alive and so gives more weight to early and midlife deaths. Five compounds that had failed the log-rank test passed the Gehan test: metformin, enalapril and 17-DMAG in males, CAPE and green tea extract in females. The authors are explicit that this pattern is what you would expect from a compound that lowers mortality before midlife and then stops helping, that these effects are "limited to midlife and may not be effective at older ages", and no correction for the number of comparisons is reported. A Gehan-only result therefore means: fewer mice died young, the survival curves converged later, and the effect on maximum lifespan was nil.
For enalapril specifically, the male survival curves violated the proportional hazards assumption, which is the technical justification for preferring Gehan, and the Gehan p value was 0.046. Set against the Interventions Testing Program's own standard, enalapril has not extended mouse lifespan; set against the reanalysis, it reduced male deaths before midlife. Both statements are true and the second is the weaker claim. There is no economic reason this will be resolved: enalapril is a generic worth pennies, and no sponsor will fund a lifespan trial of it in healthy people. Without one, neither benefit nor harm in that population will be measured.
The evidence, charted
Fig. 1 · evidence composition
3of 5 citations (60%) are in people
Counted from the citation list on this page. The Human count is the same number shown in the badge at the top. Both understate any literature larger than the sources we cite.
Fig. 2 · evidence over time
Evidence spans 5 distinct years, 1987 to 2024, counted from the citation list on this page.
Fig. 3 · legal status at a glance
US
Approved
UK
Approved
AU
Approved
CA
Approved
Approved in all four jurisdictions shown. A jurisdiction's classification is a regulatory fact, not a verdict on the science; see Legal status below for the full text and any notes.
Key studies & citations
- Animal2024
The Gehan test identifies life-extending compounds overlooked by the log-rank test in the NIA Interventions Testing Program: metformin, enalapril, caffeic acid phenethyl ester, green tea extract, and 17-DMAG
Reanalysis of 132 ITP comparisons from 2004 to 2022. Enalapril 120 ppm from 4 months, 170 treated males against 357 controls: median lifespan +7 percent, log-rank p = 0.22 (not significant), Gehan p = 0.046, proportional hazards assumption violated. No female effect. No multiplicity correction reported. The authors describe the benefit as limited to midlife. NIA funded.
GeroScience - Animal2009
Rapamycin fed late in life extends lifespan in genetically heterogeneous mice
The ITP report whose cohort included enalapril and CAPE as agents that did not significantly extend lifespan by log-rank test in either sex, alongside the landmark rapamycin result. NIA funded.
Nature - Human1987
Effects of enalapril on mortality in severe congestive heart failure: results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS)
253 patients with NYHA class IV heart failure, double-blind, enalapril 2.5 to 40 mg a day or placebo on top of conventional therapy. Six-month mortality 26 versus 44 percent (40 percent reduction, p = 0.002); one-year 31 percent reduction; 50 versus 68 deaths overall (27 percent). Entire benefit in progressive heart failure deaths, none in sudden death. Hypotension withdrawals 7 versus 0. Funding not stated in the abstract retrieved.
New England Journal of Medicine - Human1991
Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure (SOLVD Treatment)
2,569 patients with symptomatic heart failure and ejection fraction 0.35 or below, enalapril 2.5 to 20 mg a day or placebo, mean follow-up 41.4 months. Deaths 452 (35.2 percent) versus 510 (39.7 percent), risk reduction 16 percent (95 percent CI 5 to 26, p = 0.0036); death or heart failure hospitalisation 613 versus 736 (26 percent reduction). Run by the US National Heart, Lung, and Blood Institute.
New England Journal of Medicine - Human1992
Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions (SOLVD Prevention)
4,228 asymptomatic people with ejection fraction 0.35 or below, mean follow-up 37.4 months. Total mortality 313 versus 334 deaths, risk reduction 8 percent (95 percent CI -8 to 21, p = 0.30), not significant. Death or development of heart failure 630 versus 818 (29 percent reduction, p < 0.001). The null mortality result in people without symptoms is the relevant one for anyone reading enalapril as a longevity drug.
New England Journal of Medicine
Frequently asked questions
Did enalapril extend lifespan in the ITP?
Not by the programme's protocol test. Male median lifespan rose 7 percent at 120 ppm from 4 months but the log-rank p value was 0.22, and females showed nothing. A 2024 reanalysis using the Gehan test, which weights early deaths more heavily, found the male effect significant at p = 0.046, with no multiplicity correction across 132 comparisons. The reanalysis authors describe the effect as limited to midlife.
What does "Gehan-only" mean?
The log-rank test treats every death equally and looks for a proportional reduction in mortality across life. The Gehan test weights each death by how many animals are still alive, so it is more sensitive to deaths early and in midlife. A compound that is significant by Gehan but not log-rank reduced early deaths while the survival curves converged later. It is a real signal, and a narrower one than "extended lifespan".
Does enalapril reduce mortality in people?
In heart failure, yes, and the numbers are large: 40 percent relative reduction at six months in the sickest patients (CONSENSUS) and 16 percent over 3.4 years in symptomatic heart failure (SOLVD Treatment). In people with a weak heart but no symptoms, mortality was not significantly reduced (SOLVD Prevention). No trial has tested it in healthy people for longevity.
Should a healthy person take enalapril to live longer?
No trial has asked that question, so no evidence answers it. What is known is that in people without heart failure symptoms the mortality effect was not significant, and that the drug carries real side effects including hypotension, cough, raised potassium and rare angioedema. The mouse signal is a reanalysis result in males that the authors say fades with age.