Lisinopril vs Losartan
## Overview
Lisinopril (ACE inhibitor) and losartan (angiotensin receptor blocker, ARB) both block the renin-angiotensin-aldosterone system (RAAS) but at different points. ACEi reduce angiotensin II production and bradykinin breakdown; ARBs block the AT1 receptor directly. The clinical effects are largely similar, but their side effect profiles differ crucially — ACEi cause cough (~15%) due to bradykinin accumulation; ARBs do not.
## Mechanism of Action
Lisinopril: inhibits ACE, preventing angiotensin I → angiotensin II conversion, and also prevents bradykinin degradation. Elevated bradykinin contributes to vasodilation and the class-side effect of cough (and rarely angioedema). Losartan: blocks AT1 receptors, preventing angiotensin II's vasoconstrictive and aldosterone-stimulating effects, while allowing angiotensin II to act on AT2 receptors (potentially cardioprotective).
## Pharmacokinetics
Lisinopril: active drug (not prodrug), renally cleared, 25% bioavailability, once daily, half-life ~12 h. Losartan: prodrug partially converted by CYP2C9 to active E-3174 (10–40× more potent), uricosuric, once daily, half-life 2 h (parent), 9 h (E-3174).
## Clinical Evidence and Indications
Both are evidence-based for hypertension, HFrEF, and diabetic nephropathy. ACEi are guideline-preferred first-line for diabetic nephropathy and post-MI LV dysfunction. ARBs are recommended when ACEi are not tolerated (primarily due to cough). ONTARGET trial showed ACEi and ARB are equivalent in high-risk patients; combination is not recommended (increased renal toxicity without additive benefit).
## Cough and Angioedema
ACEi cough: ~15% of patients (higher in East Asian patients, up to 40%). Bradykinin-mediated, non-allergic, dose-independent. Resolves within days of stopping. ARB switch (losartan) resolves the cough. Angioedema: rare with ACEi (~0.1–0.5%), can be life-threatening. ARBs have a very low angioedema rate, but are technically contraindicated after ACEi-induced angioedema (shared class risk, though much lower).
## Pregnancy
Both ACEi and ARBs are absolutely contraindicated in pregnancy (teratogenic — cause fetal renal dysgenesis, oligohydramnios, skull hypoplasia). This is a class-wide effect via RAAS suppression.
## Key Takeaways
- ACEi (lisinopril): first-line for most RAAS indications; bradykinin-mediated cough ~15%
- ARB (losartan): preferred when ACEi not tolerated; losartan uricosuric (gout benefit)
- Both equally effective for BP, HF, CKD protection; avoid combination
Fazit
Lisinopril (ACE inhibitor) is the first-line RAAS inhibitor for hypertension, HFrEF, and diabetic nephropathy. Losartan (ARB) is the preferred alternative when ACEi is not tolerated (cough, angioedema). Losartan is specifically preferred in patients with gout or hyperuricemia due to its uricosuric effect. Combination of ACEi + ARB should be avoided.