Which angiotensin-converting enzyme (ACE) inhibitor starts with the letter L?

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Lisinopril is the ACE Inhibitor That Starts with "L"

Lisinopril is the primary ACE inhibitor starting with the letter "L" and is widely used for hypertension, heart failure, and post-myocardial infarction. 1, 2, 3

Available ACE Inhibitors Starting with "L"

Lisinopril (brand names Prinivil, Zestril) is the main ACE inhibitor beginning with "L" that appears in major clinical guidelines and has extensive evidence for cardiovascular indications. 1, 2, 4

Clinical Profile of Lisinopril

Mechanism and Pharmacology

  • Lisinopril is a lysine analogue of enalaprilat that directly inhibits angiotensin-converting enzyme without requiring metabolic activation, unlike most other ACE inhibitors which are prodrugs. 4, 5, 6

  • Peak serum concentrations occur 6-8 hours after oral administration, with antihypertensive effects beginning within 2 hours and lasting at least 24 hours, allowing once-daily dosing. 3, 5

  • Bioavailability is approximately 25% and is not significantly affected by food, making it convenient for patients. 5, 6

  • Lisinopril is excreted unchanged in the urine without hepatic metabolism or protein binding, which simplifies its use but requires dose adjustment in renal impairment. 3, 5, 6

Evidence-Based Dosing

  • For hypertension: Start at 10 mg daily and titrate to a goal dose of 20-40 mg daily. 1

  • For heart failure with reduced ejection fraction: Initiate at 2.5-5 mg once daily and titrate to the target dose of 20-40 mg once daily as tolerated. 1, 2

  • Post-myocardial infarction: The GISSI-3 trial demonstrated mortality reduction when lisinopril was started within 24 hours of symptom onset, with benefits observed in both elderly and younger patients. 7

  • High-dose lisinopril (32.5-35 mg/day) showed significantly lower mortality compared to low-dose lisinopril (2.5-5 mg/day) in the ATLAS trial, emphasizing the importance of titrating to target doses rather than stopping at lower doses. 2

Clinical Advantages

  • Lisinopril produces smooth, gradual blood pressure reduction without affecting heart rate or cardiovascular reflexes, and does not cause compensatory tachycardia. 3, 5

  • It has natriuretic properties while maintaining or increasing renal blood flow, making it particularly useful in patients with hypertension and chronic kidney disease. 5

  • Unlike thiazide diuretics, lisinopril does not produce hypokalemia, hyperglycemia, hyperuricemia, or hypercholesterolemia. 5

  • In elderly patients (age ≥65 years), response rates of 68-89% have been documented with dosages ranging from 2.5-40 mg/day, with age-related differences in efficacy not being clinically significant. 7

Safety Monitoring

  • Never exceed 40 mg once daily—if blood pressure control is inadequate at maximum dose, add a different antihypertensive class rather than exceeding this limit. 2

  • Monitor serum creatinine, estimated glomerular filtration rate, and potassium within 1-2 weeks after initiation or dose increases, then at least annually. 1

  • An increase in creatinine up to 50% above baseline or up to 3 mg/dL is acceptable, but seek specialist consultation if creatinine rises by 100% or exceeds 4 mg/dL. 8

  • Watch for ACE inhibitor-related adverse effects including hypotension, worsening renal function, hyperkalemia (particularly when combined with other RAAS inhibitors or potassium-sparing agents), dry cough, and angioedema. 2

  • In patients with severe renal impairment (creatinine clearance <30 mL/min), significant accumulation occurs and dosage reduction is necessary. 5

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

ACE Inhibitor Selection and Management in Cardiovascular Disease

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

The clinical pharmacology of lisinopril.

Journal of cardiovascular pharmacology, 1987

Guideline

Valsartan Dosage Guidelines for Hypertension and Heart Failure

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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