Angiotensin-converting enzyme inhibitors (ACEi)
ATC code: C09AA02 (Enalapril)
Brand names
Vasotec, Epaned
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.
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.
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.
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
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.
10 pairs found. Sorted from critical to minor.
Mechanism
Dual RAAS blockade at two levels: enalapril blocks angiotensin II formation, losartan blocks the binding of residual angiotensin II to the AT1 receptor. The ONTARGET (2008) and ALTITUDE (2012) trials showed no added mortality benefit and increased risks of hyperkalemia, hypotension, and acute kidney injury. and the recommend avoiding the combination.
Management
Do not combine an ACE inhibitor with an ARB. If a patient has ACE-inhibitor cough, switch to an ARB. If stronger RAAS blockade is needed, add a mineralocorticoid receptor antagonist (with potassium monitoring) rather than a second RAAS blocker.
Sources
Mechanism
Aspirin's COX inhibition reduces renal prostaglandin-mediated vasodilation. In patients with already-compromised renal perfusion (HF, dehydration, CKD) combined with an ACE inhibitor, acute kidney injury and loss of antihypertensive effect can occur. The effect is clearly dose-dependent. Antiplatelet aspirin doses of 75–100 mg predominantly inhibit platelet COX-1 and barely affect renal prostaglandins. Analgesic and antipyretic doses of 500–1000 mg inhibit COX-1 and COX-2 systemically and are comparable to other nonselective NSAIDs in their effect on renal hemodynamics and BP ( Drug Safety Communication, July 2015; Scientific Statement on NSAIDs and CV risk, Circulation 2007).
Management
Antiplatelet aspirin doses of 75–100 mg are compatible with ACE inhibitors – no adjustment needed. Analgesic and antipyretic doses of 500–1000 mg, when required, should be limited to the shortest possible course (3–5 days) and ideally replaced with paracetamol. For NSAID courses longer than 5 days, check creatinine, potassium, and BP at 7–10 days. In patients with eGFR below 60 mL/min and/or aged over 75, analgesic-dose aspirin should be avoided altogether.
Mechanism
Триметоприм блокирует эпителиальные Na-каналы в собирательных трубочках по механизму амилорида, что вызывает гиперкалиемию. Аддитивно с .
Management
Контроль K на 4-й и 7-й день курса. У пожилых и при – избегать длительных курсов.
Mechanism
In patients with activated RAAS (significant hypovolemia from aggressive diuresis, severe HF), the first ACE-inhibitor dose can cause an abrupt BP drop with syncope and acute kidney injury. With chronic use, the combination provides synergistic antihypertensive effect.
Management
Before starting an ACE inhibitor, assess volume status and, where possible, hold or reduce furosemide for 24–48 hours. Begin enalapril at the lowest dose (2.5 mg) at night while the patient is recumbent. Check BP, creatinine, and potassium at 3–7 days.
Sources
Mechanism
Synergistic BP reduction (a target combination in hypertension – even an enalapril/hydrochlorothiazide fixed-dose product exists). Hypovolemia can cause an abrupt BP drop and acute kidney injury at the first ACE-inhibitor dose. Hydrochlorothiazide shifts the RAAS toward activation, amplifying the first-dose ACE-inhibitor effect.
Management
Start both at low doses. Confirm normovolemia before initiating the ACE inhibitor – hold the thiazide for 24–48 hours if needed. Check BP (including orthostatic measurement), creatinine, and potassium at 3–7 days.
Sources
Mechanism
снижают синтез простагландинов, которые поддерживают почечный кровоток при сниженном . Риск острого почечного повреждения, особенно у пожилых и при сопутствующем приеме диуретиков («тройной удар»).
Management
Избегать длительного курса. При необходимости – минимальные дозы, контроль креатинина и калия через 3–7 дней.
Mechanism
Dual blockade of the renin-angiotensin-aldosterone system. Enalapril reduces aldosterone synthesis while spironolactone blocks the aldosterone receptor – synergistic potassium retention. Risk of severe hyperkalemia (above 6.0 mmol/L) with arrhythmias, particularly in patients over 75, with CKD (eGFR below 45 mL/min), diabetes, or dehydration.
Management
The combination is indicated in HFrEF with LVEF below 35 % (mortality benefit – RALES, EMPHASIS-HF) but requires strict monitoring. Start spironolactone at 12.5–25 mg. Check potassium and creatinine on day 3–5, at 1, 2, 4 weeks, then monthly. If K+ exceeds 5.5 mmol/L, reduce the dose or stop spironolactone. Do not combine with potassium supplements or potassium-containing salt substitutes.
Sources
Mechanism
Synergistic BP reduction via two mechanisms: amlodipine causes vasodilation, enalapril blocks the RAAS. The effect is desired in hypertension (fixed-dose combinations exist). In older patients, symptomatic hypotension – especially orthostatic – can occur.
Management
Start both drugs at low doses in older patients. Perform an orthostatic test at the first visit and at 2 weeks. For dizziness, reduce the dose of one component.
Sources
Mechanism
ACE inhibitors improve tissue insulin sensitivity and potentiate metformin's glucose-lowering effect. ACE inhibitors alone do not cause hypoglycemia, but when combined with insulin or sulfonylureas, hypoglycemia risk rises.
Management
Standalone metformin dose adjustment is usually not needed. In patients on insulin or sulfonylureas, be prepared to adjust insulin when starting the ACE inhibitor. Check at 3 months.
Sources
Mechanism
A target combination in HFrEF and hypertension – synergistic BP and pre/afterload reduction. In older patients with hypovolemia or CKD, symptomatic hypotension and bradycardia can occur.
Management
Start both at low doses and titrate slowly. Check BP, heart rate, creatinine, and potassium at 1–2 weeks and with each dose increase.
Sources
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.
Passes into breast milk in minimal amounts. Per LactMed, enalapril is compatible with breastfeeding in term infants over 1 month old with monitoring for hypotension and hyperkalemia. In preterm infants and during the first weeks of life, an alternative drug or temporary formula feeding is preferred — neonatal renal clearance may not handle even low enalaprilat concentrations.
enalapril is evaluated for the following indications with varying evidence strength: Heart failure (evidence tier A), Post-MI left ventricular dysfunction (evidence tier A), Chronic kidney disease (evidence tier A). See the full indication matrix with dosing and citations above on this page.
Common side effects of enalapril (≥ 1 in 100): Dry non-productive cough (5–20 %, more common in women), Hypotension, orthostatic symptoms, Hyperkalemia, Dizziness, Creatinine elevation. See the Safety section for uncommon and serious reactions.
FDA category 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.
Passes into breast milk in minimal amounts. Per LactMed, enalapril is compatible with breastfeeding in term infants over 1 month old with monitoring for hypotension and hyperkalemia. In preterm infants and during the first weeks of life, an alternative drug or temporary formula feeding is preferred — neonatal renal clearance may not handle even low enalaprilat concentrations.
enalapril is contraindicated in: 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. Full list in the Safety section.
there is no physiological dependence. Abrupt discontinuation in HF is permissible but not preferred — symptoms may return. In hypertension, BP gradually returns to baseline.
the ACEi-induced dry non-productive cough does not resolve while the drug is taken. If it is bothersome, switch to an ARB.