Lisinopril vs Losartan
Clinical Comparison
Clinical Context
ACE inhibitors (like lisinopril) are first-line per NICE for hypertension in under-55s and non-Black patients, and for heart failure. ARBs (like losartan) are the recommended alternative when ACEi cough or angioedema occurs. They should never be combined.
Drug Profiles
Lisinopril
ACE inhibitor
Mechanism
Inhibits angiotensin-converting enzyme, preventing the conversion of angiotensin I to angiotensin II, reducing aldosterone secretion and peripheral vasoconstriction
Indications
- Hypertension
- Heart failure
- Post-myocardial infarction
- Diabetic nephropathy
Common Doses
10 mg OD initially; titrate to 20-40 mg OD (max 80 mg in HF)
Route
Oral
Onset & Duration
Onset 1-2 hours; peak 6-8 hours; duration 24 hours
Losartan
Angiotensin II receptor blocker (ARB)
Mechanism
Selectively blocks the angiotensin II type 1 (AT1) receptor, preventing vasoconstriction and aldosterone release without affecting bradykinin metabolism
Indications
- Hypertension
- Diabetic nephropathy in type 2 diabetes
- Heart failure (when ACEi not tolerated)
- Stroke prevention in hypertensive LVH (LIFE trial)
Common Doses
50 mg OD, increased to 100 mg OD
Route
Oral
Onset & Duration
Onset 1-2 hours; peak 3-4 hours; duration 24 hours
Key Differences
| Category | Lisinopril | Losartan |
|---|---|---|
| Cough | 10-15% develop dry cough (bradykinin accumulation) | No cough — does not affect bradykinin |
| Angioedema risk | Higher risk (0.1-0.5%) | Very low risk (still possible but much rarer) |
| Heart failure evidence | Stronger mortality evidence (ATLAS, SOLVD trials) | Used when ACEi not tolerated; less direct HF mortality data |
| Uric acid effect | No significant effect on uric acid | Mild uricosuric — lowers serum uric acid (unique among ARBs) |
| Metabolism | No hepatic metabolism — renally cleared | Hepatic prodrug activation via CYP2C9/3A4 |
| NICE position | First-line RAAS blocker | Second-line — if ACEi not tolerated |
Cough
10-15% develop dry cough (bradykinin accumulation)
No cough — does not affect bradykinin
Angioedema risk
Higher risk (0.1-0.5%)
Very low risk (still possible but much rarer)
Heart failure evidence
Stronger mortality evidence (ATLAS, SOLVD trials)
Used when ACEi not tolerated; less direct HF mortality data
Uric acid effect
No significant effect on uric acid
Mild uricosuric — lowers serum uric acid (unique among ARBs)
Metabolism
No hepatic metabolism — renally cleared
Hepatic prodrug activation via CYP2C9/3A4
NICE position
First-line RAAS blocker
Second-line — if ACEi not tolerated
Key Advantages
Lisinopril
- No hepatic metabolism — useful in liver disease
- Once-daily dosing
- Proven mortality benefit in HF (ATLAS trial)
- Renoprotective in diabetic nephropathy
- Long track record of use
Losartan
- No cough (does not affect bradykinin)
- Much lower angioedema risk than ACEi
- Mild uricosuric effect — reduces serum uric acid
- Proven stroke prevention in hypertensive LVH (LIFE trial)
- Well-tolerated alternative to ACE inhibitors
Key Cautions
Lisinopril
- Dry cough in 10-15% (bradykinin accumulation)
- Angioedema (rare but potentially life-threatening)
- Hyperkalaemia — monitor potassium
- Contraindicated in pregnancy
- First-dose hypotension in volume-depleted patients
Losartan
- Less HF mortality data than ACE inhibitors
- Hyperkalaemia risk (same as ACEi)
- Contraindicated in pregnancy
- Avoid combining with ACEi (ONTARGET: no benefit, more harm)
- Prodrug — hepatic activation required (CYP2C9/3A4)
Clinical Verdict
Start with an ACE inhibitor (lisinopril) as first-line for hypertension and heart failure. Switch to losartan if the patient develops cough or angioedema. Do not combine ACEi + ARB.
Medical Disclaimer: This comparison is for educational purposes only and is not a substitute for professional medical advice. Always consult a qualified healthcare professional before making prescribing decisions. Verify all drug information with current clinical guidelines (BNF, NICE, SmPCs).
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