Most Commonly Used ACE Inhibitor or ARB
Lisinopril is the most commonly prescribed ACE inhibitor, while losartan is the most frequently used ARB in clinical practice 1.
Clinical Context and Prescribing Patterns
The evidence indicates that ACE inhibitors, particularly lisinopril, are prescribed more frequently than ARBs for several practical reasons 1:
- Longer track record of clinical use dating back to the late 1980s
- Lower cost compared to ARBs
- Extensive evidence base supporting cardiovascular protection
Key Differences Between ACE Inhibitors and ARBs
Efficacy Considerations
While both drug classes have similar blood pressure-lowering efficacy 2, 3, 4, recent high-quality evidence suggests ACE inhibitors may provide superior cardiovascular protection:
- ACE inhibitors demonstrate greater reduction in cardiovascular mortality compared to ARBs (statistically significant difference, p=0.03) 5
- ACE inhibitors reduce all-cause mortality (HR 0.92), CV mortality (HR 0.88), and myocardial infarction (HR 0.83) 5
- A 2025 multidatabase study found ARB initiation was associated with lower all-cause mortality (HR 1.13 for ACE inhibitors vs ARBs) and fewer major adverse cardiovascular events 6
Important caveat: The evidence is contradictory, with the most recent 2025-2026 studies showing conflicting results regarding mortality benefits.
Tolerability Profile
ARBs have superior tolerability 2, 3, 4:
- Lower incidence of cough (similar to placebo rates) 7
- Reduced risk of angioedema (though still possible)
- Lower overall withdrawal rates due to adverse events 2
ACE inhibitor-induced cough occurs due to bradykinin accumulation and affects a significant proportion of patients 7.
Practical Prescribing Algorithm
For new initiations:
Start with an ACE inhibitor (lisinopril) if no contraindications exist, given the stronger cardiovascular mortality data from the 2026 meta-analysis 5
Switch to an ARB (losartan) if:
- Persistent or intolerable cough develops (Grade A recommendation) 7
- Angioedema occurs (absolute indication)
- Patient cannot tolerate ACE inhibitor side effects
Consider ARB as first-line in patients who:
- Have history of ACE inhibitor intolerance
- Are particularly concerned about cough (affects quality of life)
- May benefit from potentially neuroprotective effects 4
Common Pitfalls
- Do not rechallenge with ACE inhibitors after angioedema - this is dangerous
- Allow 1-4 weeks (up to 3 months in some cases) for cough resolution after ACE inhibitor discontinuation before confirming the diagnosis 7
- Avoid combination ACE inhibitor + ARB therapy - increases adverse events without additional benefit 8
- Monitor renal function and potassium closely in both drug classes, especially with volume depletion or renal artery stenosis 9