Lisinopril vs Ramipril
## Overview
Lisinopril and ramipril are both widely used ACE inhibitors with Class I recommendations for hypertension, HFrEF, and post-MI LV dysfunction. Ramipril has landmark outcome data from the HOPE trial establishing cardiovascular protection in high-risk patients without overt HF.
## Mechanism of Action
Both inhibit ACE, reducing angiotensin II production and bradykinin breakdown. Ramipril is a prodrug (ethyl ester) hydrolyzed to the active ramiprilat, which binds ACE with high affinity (Kd ~0.1 nM). Lisinopril is the active form.
## Pharmacokinetics
Ramipril: bioavailability ~60%, half-life (ramiprilat) ~13–17 h (effective), high protein binding (73%), requires prodrug hydrolysis. Lisinopril: bioavailability ~25%, no metabolism, renal excretion, half-life ~12 h.
## Clinical Evidence
The HOPE trial (ramipril 10 mg/day) demonstrated a 22% reduction in the composite of MI, stroke, and cardiovascular death in high-risk patients without overt HF or low EF — establishing ramipril as a cardiovascular protective agent beyond blood pressure lowering. Lisinopril also has robust cardiovascular data (ATLAS, GISSI-3 post-MI), but the HOPE evidence is distinctly ramipril-driven.
## Key Takeaways
- Ramipril: HOPE trial evidence for broad cardiovascular protection in high-risk patients
- Lisinopril: renally cleared, not a prodrug; preferred in liver disease
- Both Class I for HFrEF, hypertension, post-MI LV dysfunction
الخلاصة
Ramipril is particularly preferred when the goal is broad cardiovascular risk reduction in high-risk patients (HOPE indication). Lisinopril is preferred in liver disease. Both are interchangeable for standard hypertension and HFrEF indications.