Enalapril

• Hypertension in adults and children
• Heart failure mortality reduction
• Asymptomatic left ventricular dysfunction
• Diabetic nephropathy protection
• Cardiovascular risk reduction

Enalapril is an angiotensin-converting enzyme (ACE) inhibitor that has been a cornerstone of cardiovascular medicine for decades. By blocking the conversion of angiotensin I to angiotensin II, it provides effective treatment for hypertension, heart failure, and asymptomatic left ventricular dysfunction, with proven benefits for reducing cardiovascular morbidity and mortality.

Mechanism of Action

Enalapril is a prodrug that is hydrolyzed in the liver to its active form, enalaprilat. Enalaprilat inhibits angiotensin-converting enzyme (ACE), preventing the conversion of angiotensin I to the potent vasoconstrictor angiotensin II. This results in decreased aldosterone secretion, reduced sodium and water retention, and vasodilation. Additionally, ACE inhibition decreases the breakdown of bradykinin, a vasodilator peptide, which contributes to the blood pressure-lowering effect but may also be responsible for the characteristic dry cough that occurs in some patients.

The neurohormonal modulation provided by ACE inhibitors extends beyond blood pressure control. In heart failure, enalapril reduces preload and afterload, decreases ventricular remodeling, and provides long-term cardiovascular protection that translates to improved survival and reduced hospitalizations.

Available Formulations

Enalapril maleate is available as oral tablets in 2.5 mg, 5 mg, 10 mg, and 20 mg strengths. Enalaprilat, the active metabolite, is available as an injectable solution (1.25 mg/mL) for intravenous use when oral administration is not feasible. A combination product with hydrochlorothiazide (Vaseretic) is available for patients requiring dual therapy.

FDA-Approved Indications

Enalapril is FDA-approved for hypertension in adults and pediatric patients one month of age and older, symptomatic heart failure (to reduce mortality and hospitalizations), and asymptomatic left ventricular dysfunction with ejection fraction 35% or less (to decrease rate of development of overt heart failure and reduce hospitalization for heart failure). These broad indications reflect the extensive clinical trial evidence supporting the cardiovascular benefits of ACE inhibition.

Dosing Guidelines

For hypertension, the typical starting dose is 5 mg once daily, with a usual dose range of 10-40 mg daily in one or two divided doses. For heart failure, start with 2.5 mg once or twice daily, titrating gradually to target doses of 10-20 mg twice daily as tolerated. Lower starting doses (2.5 mg) are recommended for patients with renal impairment, those on diuretics, or those at risk for hypotension. Monitor blood pressure, renal function, and potassium levels, especially during dose initiation and titration.

Clinical Trial Evidence

Enalapril has been studied extensively in landmark clinical trials that established the role of ACE inhibitors in cardiovascular medicine. The CONSENSUS and SOLVD trials demonstrated mortality reduction in heart failure. The SOLVD Prevention trial showed benefits in asymptomatic LV dysfunction. These trials, along with extensive post-marketing experience, have made enalapril one of the most well-characterized cardiovascular medications.

Important Safety Considerations

Enalapril carries a boxed warning for fetal toxicity; it should be discontinued immediately when pregnancy is detected due to risks of fetal injury and death. Angioedema can occur, particularly affecting the face, lips, tongue, and larynx, and may be life-threatening; it is more common in African American patients. Hyperkalemia may develop, especially in patients with renal impairment or those taking potassium supplements or potassium-sparing diuretics. Hypotension may occur, particularly with first doses in patients who are volume-depleted.

Drug Interactions

NSAIDs can reduce the antihypertensive effect and increase the risk of renal impairment. Potassium supplements and potassium-sparing diuretics increase the risk of hyperkalemia. Lithium levels may increase; monitor closely. Dual blockade of the renin-angiotensin system with ARBs or aliskiren is generally not recommended due to increased risks of hypotension, hyperkalemia, and renal impairment. Diuretics may enhance hypotensive effects.

Special Populations

Dose reduction is required in renal impairment based on creatinine clearance. Use with caution in patients with bilateral renal artery stenosis or stenosis in a solitary kidney due to risk of acute renal failure. Enalapril is contraindicated during pregnancy. Safety and dosing have been established in pediatric patients one month of age and older for hypertension. Elderly patients may require lower starting doses due to age-related decreases in renal function.

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