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. ESC HF 2021 now prefers sacubitril/valsartan, but enalapril remains an evidence-based alternative.

Sources

ESC: 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure (2021)

Hypertension

First line

First-line antihypertensive per ESC/ESH 2024 and ACC/AHA 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

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.

Safety

Contraindications

Pregnancy (all trimesters)
History of ACE inhibitor-induced angioedema
Bilateral renal artery stenosis or stenosis of a single functioning kidney
Severe hyperkalemia
Concurrent aliskiren in patients with diabetes and CKD

Serious adverse effects

Angioedema (rare, life-threatening with airway involvement)
Acute kidney injury (in hypovolemia, renal artery stenosis, concurrent NSAIDs)
Severe hyperkalemia

Common adverse effects

Dry non-productive cough (5–20 %, more common in women)
Hypotension, orthostatic symptoms
Hyperkalemia
Dizziness
Creatinine elevation

Uncommon adverse effects

Rash, pruritus
Dysgeusia
Proteinuria

PregnancyFDA D

FDA category D. Use in the second and third trimesters is associated with oligohydramnios, pulmonary hypoplasia, skull and limb deformities, neonatal hypotension, and AKI. Current data suggest potential first-trimester risks as well. Discontinue on confirmation of pregnancy.

Breastfeeding

Passes into breast milk in minimal amounts. Compatible with breastfeeding in infants over 1 month old when no alternative is clinically required.