Enalapril

Angiotensin-converting enzyme inhibitors (ACEi)

ATC code: C09AA02 (Enalapril)

Brand names

Vasotec, Epaned

Mechanism of action

Prodrug converted in the liver to enalaprilat, a competitive ACE inhibitor. Blocks conversion of angiotensin I to angiotensin II, producing vasodilation, reduced aldosterone secretion, and decreased sodium and water retention. It also slows bradykinin degradation, which partly explains the dry cough side effect.

Indications

Chronic kidney disease

First line

ACE inhibitors slow progression of chronic kidney disease in patients with albuminuria, particularly in diabetic nephropathy. Target blood pressure depends on albuminuria level. Check creatinine and potassium 1–2 weeks after initiation and each dose increase; a rise of up to 30 % in creatinine is acceptable. Discontinue for larger rises or persistent hyperkalemia.

Sources

Heart failure

First line

ACE inhibitors are one of the four pillars of HFrEF therapy together with beta-blockers, MRAs, and SGLT2 inhibitors. They reduce all-cause mortality and hospitalizations. Start low (2.5 mg BID) and titrate to maximum tolerated dose monitoring blood pressure, renal function, and potassium. HF 2021 now prefers sacubitril/valsartan, but enalapril remains an evidence-based alternative.

Sources

Hypertension

First line

First-line antihypertensive per 2024 and 2017. Start at 5 mg once daily, titrate to 10–20 mg 1–2 times daily. Particularly preferred in comorbid T2D, CKD, HFrEF, and post-MI states. In Black patients, monotherapy is less effective; CCBs or thiazide-like diuretics are often chosen.

Sources

Post-MI left ventricular dysfunction

First line

Early initiation of ACE inhibitors (within the first 24 h when hemodynamically stable) after myocardial infarction with reduced LVEF reduces mortality, reinfarction, and heart failure progression. Evidence from SAVE, AIRE, TRACE, and SOLVD trials.

Sources

Marketing claims without evidence base

The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.

Anti-aging and longevity

Not recommended

Enalapril is a long-acting ACE inhibitor. It is prescribed for hypertension, heart failure, after myocardial infarction, and for diabetic nephropathy ( 2023, SEH-LELHA). In anti-aging regimens, enalapril is given to healthy normotensives for general cardioprotection and to slow vascular aging. In people with normal blood pressure and no confirmed pathology, no clinical studies of prophylactic use exist. The drug causes a dry cough (10-20% of patients), hyperkalemia, dizziness, angioedema in predisposed people, and teratogenicity (contraindicated in pregnancy). If enalapril was prescribed to a healthy person, consider seeking a second opinion.

Sources

Practical notes

Timing and administration

Take with or without food. The first dose may cause pronounced hypotension ('first-dose hypotension'), especially in hypovolemic patients, those with high plasma renin activity, or severe heart failure. In these patients, the first dose is taken at bedtime after a baseline BP measurement.

Monitoring

Check serum creatinine and potassium 1–2 weeks after initiation, after each dose increase, and during intercurrent illness with dehydration risk. A creatinine rise up to 30 % and potassium up to 5.5 mmol/L are acceptable. Larger changes require workup (renal artery stenosis, hypovolemia, concurrent NSAIDs, diuretics).

Special situations

Contraindicated in pregnancy (all trimesters, not only the second and third as previously thought). Discontinue when pregnancy is planned. If dry cough develops, switch to an ARB (losartan, valsartan, etc.) — cough risk is substantially lower. Angioedema is rare but life-threatening, more common in Black patients. If it occurs, ACE inhibitors are discontinued for life and not replaced with another drug of this class.

Common myths

Myth: 'ACE inhibitors cause dependence, discontinuation is risky'. Fact: there is no physiological dependence. Abrupt discontinuation in HF is permissible but not preferred — symptoms may return. In hypertension, BP gradually returns to baseline.

Myth: 'the cough will go away, just wait'. Fact: the ACEi-induced dry non-productive cough does not resolve while the drug is taken. If it is bothersome, switch to an ARB.

Drug–drug interactions

21 pairs found. Sorted from critical to minor.

Major

Allopurinol

Xanthine oxidase inhibitors

Mechanism

The combination raises risk of hypersensitivity reactions and severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, angioedema). Risk is higher in chronic kidney disease. Mechanism: presumed immune reaction to metabolites of both drugs.

Symptoms

Rash, fever, eosinophilia, lymphadenopathy (DRESS syndrome). Severe cases: bullous rash with skin sloughing, angioedema of face and tongue. Symptoms appear 1–8 weeks into the combination.

Management

Avoid the combination, especially in chronic kidney disease. Alternative to ACE-I: an ARB (losartan, valsartan). If rash or fever emerges, stop both drugs immediately.

Sources

Mechanism of action

Indications

Practical notes

Timing and administration

Monitoring

Special situations

Common myths

Drug–drug interactions

Check interaction with another drug

Official sources

Safety

Contraindications

Serious adverse effects

Common adverse effects

Uncommon adverse effects

PregnancyFDA D

Frequently asked

Mechanism of action

Indications

Practical notes

Timing and administration

Monitoring

Special situations

Common myths

Drug–drug interactions

Check interaction with another drug

Official sources

Safety

Contraindications

Serious adverse effects

Common adverse effects

Uncommon adverse effects

PregnancyFDA D

Frequently asked