Lisinopril vs Enalapril

## Overview

Lisinopril and enalapril are both ACE (angiotensin-converting enzyme) inhibitors widely used for hypertension, heart failure, and post-MI LV dysfunction. Lisinopril is a prodrug-independent active drug; enalapril is a prodrug requiring hepatic ester hydrolysis.

## Mechanism of Action

Both inhibit ACE (kininase II), preventing conversion of angiotensin I to angiotensin II. This reduces vasoconstriction and aldosterone secretion, lowering blood pressure and cardiac afterload. Both also inhibit bradykinin degradation, contributing to their antihypertensive effect but also causing the class-side effect of dry cough (~10–20% of patients).

## Pharmacokinetics

Lisinopril: not a prodrug, not metabolized, renally excreted unchanged, half-life ~12 h, bioavailability ~25%. Enalapril: prodrug (enalaprilat is the active diacid), hydrolyzed by hepatic esterases, half-life ~11 h, bioavailability ~60%.

## Pharmacodynamics and Clinical Evidence

Both have extensive evidence in HFrEF (ATLAS with lisinopril; CONSENSUS and SOLVD with enalapril). The ATLAS trial (lisinopril) demonstrated high-dose superiority over low-dose. Enalapril in CONSENSUS and SOLVD demonstrated landmark mortality reductions in HFrEF and asymptomatic LV dysfunction. Both are Class I recommendations for HFrEF.

## Key Takeaways

- Lisinopril: not a prodrug, renally cleared; dose adjust in CKD
- Enalapril: prodrug; hepatic esterase required (caution in severe liver disease)
- Both have excellent outcome data; enalapril's CONSENSUS/SOLVD are landmark trials