Enalapril

What it is

Enalapril is a synthetic small-molecule prescription medicine, the maleate salt of the ethyl ester of enalaprilat. It is a prodrug: after swallowing, the ester is hydrolysed to enalaprilat, which is the active angiotensin-converting-enzyme inhibitor. In the United States it is a prescription drug supplied as 2.5, 5, 10 and 20 mg tablets, originally branded Vasotec. It carries a boxed warning for fetal toxicity.

What the research says

The evidence for enalapril is unusually strong in one setting and weak in another. In symptomatic heart failure with a weak pumping chamber, two large randomised trials showed fewer deaths: six-month mortality fell from 44% to 26% in severe heart failure, and from 39.7% to 35.2% over three and a half years in milder heart failure. In people with a weak heart but no symptoms the same drug did not significantly reduce death, although it delayed heart failure. For high blood pressure the trial evidence is about lowering blood pressure and, in older people, an ACE-inhibitor strategy was at best marginally better than a diuretic. Sacubitril/valsartan has since beaten enalapril head to head. The common price is a dry cough, about twice as frequent as on placebo; the rare and dangerous one is angioedema.

Evidence grade: Well established.

How it works

Drug class: Angiotensin-converting enzyme (ACE) inhibitor (prodrug of enalaprilat)

Enalapril is converted in the body to enalaprilat, which blocks the enzyme that turns angiotensin I into angiotensin II. Angiotensin II narrows blood vessels and triggers aldosterone release, so blocking its production widens vessels, lowers blood pressure and reduces the load on a failing heart. The same enzyme breaks down bradykinin, so bradykinin levels rise, which is thought to explain the cough and angioedema. (Source 1)

Boxed warning

When pregnancy is detected, discontinue VASOTEC ® as soon as possible.

(Source 2)

What it is used for

• Enalapril reliably lowers blood pressure and is approved for hypertension in the United States. On hard outcomes in older people, an ACE-inhibitor-based strategy was only marginally better than a diuretic-based one (hazard ratio 0.89, 95% CI 0.79-1.00, P=0.05) despite identical blood pressure falls. Evidence: established. (Source 3)
• Two placebo-controlled randomised trials showed fewer deaths and fewer hospitalisations. The absolute benefit was large in severe (NYHA IV) heart failure and smaller but still clear in NYHA II-III disease. Evidence: established. (Source 4)
• Approved on the strength of preventing overt heart failure and heart failure hospitalisation. The same trial found no statistically significant reduction in death (risk reduction 8%, P = 0.30). Evidence: limited. (Source 5)
• Used off-label as cardioprotection. A systematic review of seven studies found a higher ejection fraction with enalapril but with I-squared of 96%, meaning the studies contradict each other, and the authors said more research is needed. Evidence: disputed. (Source 6)

Interactions

• Potassium supplements and potassium-containing salt substitutes (label): Enalapril raises potassium by reducing aldosterone. Adding potassium supplements, potassium-based 'low sodium' salt substitutes or potassium-sparing diuretics on top can push potassium to dangerous levels. (Source 7)
• Non-steroidal anti-inflammatory drugs, including COX-2 inhibitors (ibuprofen, naproxen, celecoxib) (label): In older, dehydrated or kidney-impaired people, combining an NSAID with enalapril can worsen kidney function, including acute kidney failure. NSAIDs may also blunt the blood-pressure effect. (Source 7)
• Lithium (case reports): Lithium levels can rise to toxic levels when an ACE inhibitor is added, reversing when both drugs are stopped. (Source 7)
• Sacubitril/valsartan and other neprilysin inhibitors, and mTOR inhibitors (sirolimus, everolimus, temsirolimus) (label): Combining these with an ACE inhibitor raises the risk of angioedema; the label makes the neprilysin inhibitor combination a contraindication and requires a 36-hour gap when switching. (Source 8)
• Melatonin (relevant where someone takes both) (clinical trial): Not an enalapril study, but a randomised crossover trial in people whose blood pressure was controlled on nifedipine found that evening melatonin raised blood pressure and heart rate over 24 hours, so the assumption that melatonin is inert in treated hypertension is not safe. (Source 9)

Stopping it

• The ACE-inhibitor cough is reversible: the label states it always resolves once the drug is stopped, which is also how the diagnosis is confirmed. (Source 10)
• Stopping is not neutral. In 1.47 million UK primary care users, among those who had an adverse reaction recorded, the half who stayed on an ACE inhibitor or ARB had lower mortality than those who stopped (adjusted hazard ratio 0.88, 95% CI 0.82 to 0.95). (Source 11)
• One stop is mandatory rather than optional: the boxed warning requires the drug to be discontinued as soon as pregnancy is detected. (Source 2)

What goes wrong

Cough is about twice as common on an ACE inhibitor as on placebo, and enalapril sits in the middle of the class for cough risk. (Source 12)

• Meta-analysis, Moderate certainty.
• Size: 135 randomised controlled trials, 45,420 patients treated with eleven ACE inhibitors.
• Who: Adults in randomised trials of ACE inhibitors versus placebo, angiotensin receptor blockers or calcium channel blockers.
• How long: Varied by trial.
• Result: Pooled relative risk of cough for ACE inhibitor versus placebo 2.21 (95% CI 2.05-2.39); versus an ARB 3.2 (2.91-3.51); versus a calcium channel blocker 5.30 (4.32-6.50). Enalapril ranked ninth of eleven ACE inhibitors (SUCRA 49.7%)
• Funding: not stated.

The pooled estimated relative risk (RR) between ACEI and placebo was 2.21 (95% CI: 2.05–2.39).

Angioedema of the face, lips, tongue or larynx can occur at any time on enalapril and can be fatal when the larynx is involved. (Source 8)

• Official position, Certainty not rated.
• Size: Not stated in this section of the label.
• Who: People treated with ACE inhibitors including enalapril.
• How long: Can occur at any time during treatment.
• Result: No rate is given in this section; the label records angioedema as more frequent in black than non-black patients and notes that laryngeal involvement may be fatal. Label version dated 23 January 2026.
• Funding: not applicable (regulatory label)

Angioedema associated with laryngeal edema may be fatal.

Raised potassium is uncommon in hypertension but affected about one in 26 heart failure patients in the registration trials. (Source 10)

• Official position, Certainty not rated.
• Size: More than 10,000 patients evaluated for safety across the enalapril programme.
• Who: Patients with hypertension or heart failure in enalapril clinical trials.
• How long: Up to three years in hypertension trials.
• Result: Serum potassium above 5.7 mEq/L in approximately 1% of hypertensive patients, causing discontinuation in 0.28%; hyperkalemia in 3.8% of heart failure patients. Label version dated 23 January 2026.
• Funding: not applicable (regulatory label)

In clinical trials in heart failure, hyperkalemia was observed in 3.8 percent of patients but was not a cause for discontinuation.

Having an adverse reaction recorded to an ACE inhibitor or ARB in primary care was followed by more cardiovascular events and deaths, and stopping the drug was worse than staying on it. (Source 11)

• Cohort study, Low certainty.
• Size: 1,471,906 users of ACE inhibitors or ARBs; 13,652 (0.93%) with a recorded adverse drug reaction consultation.
• Who: Adults prescribed ACE inhibitors or ARBs in UK primary care, 2004-2019.
• How long: Up to 15 years of records.
• Result: After an adverse reaction consultation: primary prevention cardiovascular events adjusted HR 1.22 (95% CI 1.05-1.43), all-cause mortality 1.14 (1.01-1.27); secondary prevention 1.13 (1.05-1.21) and 1.15 (1.09-1.21). Among those with a reaction, 50.19% continued and had lower mortality (aHR 0.88, 0.82-0.95) than those who stopped.
• Funding: independent (university-based, IQVIA data)

Patients with ACEIs/ARBs-related ADR consultation had an increased risk of subsequent CVD events and all- cause mortality in both primary prevention (CVD events: adjusted hazard ratio [aHR] 1.22, 95% confidence interval [CI] = 1.05 to 1.43; all-cause mortality: aHR 1.14, 95% CI = 1.01 to 1.27)

What the evidence supports

In New York Heart Association class IV heart failure, adding enalapril to conventional treatment cut six-month mortality from 44% to 26%. (Source 4)

• Randomized trial, Moderate certainty.
• Size: 253 patients (126 placebo, 127 enalapril)
• Who: Patients with severe (NYHA class IV) congestive heart failure.
• How long: Follow-up averaged 188 days (range 1 day to 20 months)
• Result: Six-month crude mortality 26% with enalapril vs 44% with placebo, an absolute difference of about 18 percentage points (about 6 people treated for 6 months to avoid one death), relative reduction 40%, P = 0.002; by study end 50 deaths vs 68, a 27% reduction, P = 0.003.
• Funding: not stated.

The crude mortality at the end of six months (primary end point) was 26 percent in the enalapril group and 44 percent in the placebo group--a reduction of 40 percent (P = 0.002).

In chronic heart failure with ejection fraction 35% or less, enalapril reduced all-cause death from 39.7% to 35.2% over a mean 41 months. (Source 13)

• Randomized trial, High certainty.
• Size: 2,569 patients (1,284 placebo, 1,285 enalapril)
• Who: Patients with chronic congestive heart failure and ejection fraction <=0.35, about 90% NYHA class II-III.
• How long: Follow-up averaged 41.4 months.
• Result: 510 deaths (39.7%) on placebo vs 452 (35.2%) on enalapril; absolute difference 4.5 percentage points (about 22 treated for ~3.5 years to avoid one death); relative risk reduction 16% (95% CI 5 to 26), P = 0.0036.
• Funding: not stated.

There were 510 deaths in the placebo group (39.7 percent), as compared with 452 in the enalapril group (35.2 percent) (reduction in risk, 16 percent; 95 percent confidence interval, 5 to 26 percent; P = 0.0036).

What the evidence does not support

In people with reduced ejection fraction but no heart failure symptoms, enalapril did not significantly reduce death; the benefit was in preventing heart failure. (Source 5)

• Randomized trial, High certainty.
• Size: 4,228 patients (2,117 placebo, 2,111 enalapril)
• Who: Asymptomatic patients with ejection fraction 0.35 or less, not on heart failure drugs.
• How long: Follow-up averaged 37.4 months.
• Result: 334 deaths on placebo vs 313 on enalapril, risk reduction 8% (95% CI -8% to 21%), P = 0.30; cardiovascular death reduction 12% (95% CI -3 to 26), P = 0.12; combined death or heart failure 818 vs 630, 29% reduction, P<0.001.
• Funding: not stated.

There were 334 deaths in the placebo group, as compared with 313 in the enalapril group (reduction in risk, 8 percent by the log-rank test; 95 percent confidence interval, -8 percent [an increase of 8 percent] to 21 percent; P = 0.30).

Enalapril is no longer the most effective renin-angiotensin drug for heart failure: sacubitril/valsartan beat enalapril on every outcome in a head-to-head trial. (Source 14)

• Randomized trial, High certainty.
• Size: 8,399 patients randomised in PARADIGM-HF (4,212 enalapril, 4,187 LCZ696)
• Who: Patients with heart failure and reduced ejection fraction already on a beta-blocker in most cases.
• How long: Median follow-up 27 months.
• Result: Against enalapril 10 mg twice daily, sacubitril/valsartan gave hazard ratios of 0.80 for cardiovascular death or heart failure hospitalisation, 0.80 for cardiovascular death and 0.84 for all-cause mortality (as tabulated in this paper)
• Funding: industry-funded (Novartis authors and funding)

In PARADIGM-HF, all outcomes were reduced significantly by LCZ696 compared with enalapril.

Where the evidence is mixed

Pooling 57 randomised heart failure trials, ACE inhibitor monotherapy was associated with a 16% lower risk of death than placebo, but the credible interval touched no effect. (Source 15)

• Meta-analysis, Moderate certainty.
• Size: 57 randomised controlled trials published 1987-2015.
• Who: Adults with chronic heart failure, left ventricular ejection fraction <45%, NYHA class II-IV.
• How long: Trial follow-up 8 weeks to 4 years.
• Result: ACE inhibitor vs placebo hazard ratio for all-cause mortality 0.84, 95% credible interval 0.65-1.01 in the sensitivity analysis ignoring background therapy; ACEI+beta-blocker+MRA vs placebo hazard ratio 0.44 (0.26-0.66)
• Funding: industry-funded (authors employed by Mapi and Novartis)

The sensitivity analysis showed that in comparison to placebo, ARNI was associated with a 29% reduction in mortality (HR 0.71, 95% CrI 0.39–1.17); ACEI, a 16% reduction (HR 0.84, 95% CrI 0.65–1.01); and ARB, a 12% reduction (HR 0.88, 95% CrI 0.65–1.17).

In older people with hypertension, an ACE-inhibitor-based strategy was at best marginally better than a diuretic-based one for cardiovascular events or death. (Source 3)

• Randomized trial, Moderate certainty.
• Size: 6,083 subjects aged 65-84 in 1,594 family practices.
• Who: Older adults with hypertension.
• How long: Median follow-up 4.1 years.
• Result: 695 cardiovascular events or deaths on ACE inhibitor (56.1 per 1000 patient-years) vs 736 on diuretic (59.8 per 1000 patient-years); hazard ratio 0.89 (95% CI 0.79 to 1.00), P=0.05; blood pressure fell equally (26/12 mm Hg) in both arms.
• Funding: not stated.

the hazard ratio for a cardiovascular event or death with ACE-inhibitor treatment was 0.89 [95 percent confidence interval, 0.79 to 1.00]; P=0.05

For the off-label use of protecting the heart during anthracycline chemotherapy, pooled enalapril data favour a higher ejection fraction but the studies disagree strongly with each other. (Source 6)

• Systematic review, Very low certainty.
• Size: Seven studies included from 626 screened.
• Who: Oncology patients receiving anthracycline chemotherapy.
• How long: Follow-up 6 to 12 months in the studies reporting deaths.
• Result: Weighted mean difference in left ventricular ejection fraction between enalapril and control 7.18 (95% CI 2.49-11.87), with I-squared 96% indicating very high heterogeneity, P < .001.
• Funding: not stated.

Limit of this finding: The review's own heterogeneity figure for this pooled result is I-squared 96%, meaning the seven small studies disagreed with each other almost completely. An average taken across studies that disagree that strongly is not a dependable effect size. Treat the 7.18-point ejection fraction difference as a signal that larger trials should test, not as a benefit anyone could expect from taking enalapril during chemotherapy.

while five of these studies showed that there was a significant difference in the left ventricular ejection fraction (LVEF) between an enalapril group and a control group (weighted mean difference (WMD) = 7.18, 95% CI: 2.49–11.87, I2 = 96%, P < .001)

Where the research disagrees

Whether ACE inhibitors are genuinely better than other first-line blood pressure drugs, or only equivalent

• ANBP2 investigators (New England Journal of Medicine, 2003), open-label randomised trial, 6,083 older adults: "the hazard ratio for a cardiovascular event or death with ACE-inhibitor treatment was 0.89 [95 percent confidence interval, 0.79 to 1.00]; P=0.05" - a borderline advantage over a diuretic despite identical blood pressure reduction (Source 3)
• Hu and colleagues (Journal of Clinical Hypertension, 2023), network meta-analysis of 135 randomised trials: "ACEI should be avoided in patients who have risk of developing cough, and an ARB or CCB is an alternative based on the patient's comorbidity." (Source 12)

Whether enalapril remains the right renin-angiotensin drug for heart failure

• SOLVD investigators (1991), randomised placebo-controlled trial, 2,569 patients: "The addition of enalapril to conventional therapy significantly reduced mortality and hospitalizations for heart failure in patients with chronic congestive heart failure and reduced ejection fractions." (Source 13)
• McMurray and colleagues, PARADIGM-HF putative placebo analysis (European Heart Journal, 2015), active-controlled randomised trial with indirect placebo comparison: "In PARADIGM-HF, all outcomes were reduced significantly by LCZ696 compared with enalapril." (Source 14)

How much

• Reference intake: There is no reference intake for a prescription drug; dosing is set by the prescriber and differs by indication. For hypertension the US label records a usual range of 10 to 40 mg a day in one or two doses, starting at 5 mg once daily in people not on a diuretic; for heart failure it records a separate starting dose of 2.5 mg and a range of 2.5 to 20 mg twice a day (label version 23 January 2026). (Source 16)
• Upper limit: The label's maximum is 40 mg a day. In heart failure the label records that 'The maximum daily dose administered in clinical trials was 40 mg in divided doses', reached from a 2.5 mg starting dose; the separate hypertension section tops its usual range out at 40 mg per day in a single dose or two divided doses (label version 23 January 2026). (Source 17)
• Studied: CONSENSUS gave enalapril 2.5 to 40 mg per day to patients with NYHA class IV heart failure. (Source 4)
• Studied: SOLVD-Treatment gave enalapril 2.5 to 20 mg per day, with a target of 10 mg twice daily. (Source 13)
• Studied: SOLVD-Prevention gave enalapril at doses of 2.5 to 20 mg per day. (Source 5)
• Studied: In PARADIGM-HF the enalapril comparator arm achieved a mean daily dose of 18.9 mg, against 16.6 mg in SOLVD-T. (Source 14)

A common belief, and what the research shows

The belief: An ACE inhibitor cough means you are allergic to the drug and should switch to another ACE inhibitor.

What the research shows: The cough is a predictable class effect from bradykinin, not an allergy, and switching within the class does not help much: the network meta-analysis of 135 trials concluded "All ACEI has the similar risk of developing a cough." Moving to an angiotensin receptor blocker or calcium channel blocker is what changes the risk - "ACEI had more incidences of cough than ARB (RR 3.2; 95% CI: 2.91, 3.51)". The separate, genuinely dangerous reaction is angioedema, where the label says "Angioedema associated with laryngeal edema may be fatal."

Questions and answers

What is it?

Enalapril is a synthetic tablet medicine, not a nutrient. It is a prodrug: the body splits off an ethyl ester to make enalaprilat, which is the molecule that actually blocks angiotensin-converting enzyme. It is sold as enalapril maleate in 2.5, 5, 10 and 20 mg tablets and under brand names such as Vasotec. (Source 2)

What does it do in the body?

Enalaprilat blocks the enzyme that converts angiotensin I into angiotensin II, a hormone that tightens blood vessels and drives aldosterone release. Less angiotensin II means wider blood vessels, lower blood pressure and less strain on a failing heart. The same enzyme also breaks down bradykinin, which is why levels of bradykinin rise. (Source 1)

Is it good or bad for you?

It depends entirely on the situation. In severe heart failure it saved lives in a trial that was stopped early, and in milder heart failure it cut deaths from 39.7% to 35.2%. In people with a weak heart but no symptoms it did not significantly reduce death. It must never be used in pregnancy, and it causes cough in roughly twice as many people as placebo. (Source 13)

How do you get more of it?

Enalapril is available only on prescription; there is no food or supplement source. In the trials and in the label, treatment starts low and is increased: the label records a usual hypertension range of 10 to 40 mg a day, and for heart failure a starting dose of 2.5 mg titrated to a usual range of 2.5 to 20 mg twice daily. The dose is set by the prescriber, not by the reader. (Source 16)

If it is harmful, what reduces it?

The way to reduce enalapril's effects is to stop it, which only a prescriber should decide. The dry cough that ACE inhibitors cause always resolves after the drug is stopped. Enalaprilat is also removed by haemodialysis. In the UK primary care cohort, however, people who stopped after an adverse reaction had higher mortality than those who continued, so stopping is not risk-free. (Source 10)

Why might someone be low in it or missing it?

Someone may not be on enalapril because it is contraindicated or not tolerated. Pregnancy is an absolute bar. Angioedema, persistent cough, raised potassium or falling kidney function lead to stopping; in UK primary care about half of people who had an adverse reaction recorded stopped ACE inhibitors or ARBs altogether. Dose is also reduced when kidney function is poor. (Source 11)

Which whole foods contain it or feed it?

No whole food contains enalapril. Food matters the other way round: potassium-rich salt substitutes and potassium supplements can push potassium up dangerously when combined with enalapril, because the drug itself reduces potassium loss. (Source 7)

What happens if you do not have it?

Enalapril is a treatment, not something the body needs. What the trials show is what happens without it in the conditions it treats: in severe heart failure 44% of the placebo group were dead within six months, and in milder heart failure 39.7% of the placebo group died over about three and a half years. (Source 4)

How can you test for it?

There is no routine test for enalapril itself. What is measured is its effect and its risks: blood pressure, and blood tests for kidney function and potassium. The label states that assessment of renal function should always be part of evaluating someone with hypertension or heart failure, and records that about 1% of hypertensive trial participants had potassium above 5.7 mEq/L. (Source 10)

References

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2. DailyMed / Bausch Health US LLC. VASOTEC- enalapril maleate tablet (US prescribing information, boxed warning and description). 2026. Read the source
3. New England Journal of Medicine. A comparison of outcomes with angiotensin-converting--enzyme inhibitors and diuretics for hypertension in the elderly.. 2003. PMID 12584366, DOI 10.1056/nejmoa021716. Read the source
4. New England Journal of Medicine. Effects of enalapril on mortality in severe congestive heart failure. Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS).. 1987. PMID 2883575, DOI 10.1056/nejm198706043162301. Read the source
5. New England Journal of Medicine. Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions.. 1992. PMID 1463530, DOI 10.1056/nejm199209033271003. Read the source
6. Frontiers in Pharmacology. Protective Role of Enalapril in Anthracycline-Induced Cardiotoxicity: A Systematic Review. 2020. PMID 32536868, DOI 10.3389/fphar.2020.00788. Read the source
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8. DailyMed / Bausch Health US LLC. VASOTEC- enalapril maleate tablet (US prescribing information, Head and Neck Angioedema). 2026. Read the source
9. British Journal of Clinical Pharmacology. Cardiovascular effects of melatonin in hypertensive patients well controlled by nifedipine: a 24-hour study.. 2000. PMID 10792199, DOI 10.1046/j.1365-2125.2000.00195.x. Read the source
10. DailyMed / Bausch Health US LLC. VASOTEC- enalapril maleate tablet (US prescribing information, hyperkalemia and cough). 2026. Read the source
11. British Journal of General Practice. Impact of ACEIs and ARBs-related adverse drug reaction on patients' clinical outcomes: a cohort study in UK primary care.. 2023. PMID 37722857, DOI 10.3399/BJGP.2023.0153. Read the source
12. The Journal of Clinical Hypertension. Angiotensin-converting enzyme inhibitor induced cough compared with placebo, and other antihypertensives: A systematic review, and network meta-analysis. 2023. PMID 37417783, DOI 10.1111/jch.14695. Read the source
13. New England Journal of Medicine. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure.. 1991. PMID 2057034, DOI 10.1056/nejm199108013250501. Read the source
14. European Heart Journal. A putative placebo analysis of the effects of LCZ696 on clinical outcomes in heart failure.. 2015. PMID 25416329, DOI 10.1093/eurheartj/ehu455. Read the source
15. Circulation: Heart Failure. Thirty Years of Evidence on the Efficacy of Drug Treatments for Chronic Heart Failure With Reduced Ejection Fraction: A Network Meta-Analysis. 2017. PMID 28087688, DOI 10.1161/CIRCHEARTFAILURE.116.003529. Read the source
16. DailyMed / Bausch Health US LLC. VASOTEC- enalapril maleate tablet (US prescribing information, Dosage and Administration: Hypertension). 2026. Read the source
17. DailyMed / Bausch Health US LLC. VASOTEC- enalapril maleate tablet (US prescribing information, Dosage and Administration: Heart Failure). 2026. Read the source