The Quick Answer
[ACE inhibitors](/drug-classes/ace-inhibitors) and [ARBs](/drug-classes/arbs) are both highly effective for [hypertension](/conditions/hypertension), [heart failure](/conditions/heart-failure), and kidney protection. ACE inhibitors are generally preferred as first-line therapy due to their longer evidence base and lower cost. ARBs are the preferred alternative when ACE inhibitor cough or angioedema occurs. The two classes should never be combined.
How They Work: The Key Difference
Both drug classes block the renin-angiotensin-aldosterone system (RAAS), but at different points:
- ACE inhibitors block the enzyme that converts angiotensin I to angiotensin II. This also prevents the breakdown of bradykinin — a vasodilatory peptide that causes the characteristic cough and (rarely) angioedema.
- ARBs block the angiotensin II receptor (AT1 receptor) directly. Angiotensin II is still formed, but it cannot bind to its receptor. Because ARBs do not affect ACE, bradykinin levels are not increased — so ARBs do not cause cough.
Side-by-Side Comparison
| Feature | ACE Inhibitors | ARBs |
|---|---|---|
| Common examples | Lisinopril, enalapril, ramipril, benazepril | Losartan, valsartan, irbesartan, olmesartan, telmisartan |
| Mechanism | Block ACE enzyme | Block AT1 receptor |
| Bradykinin effect | Increases bradykinin | No effect on bradykinin |
| Dry cough | 10–15% (up to 40% in Asians) | <1% |
| Angioedema | 0.1–0.7% | Very rare (<0.1%) |
| Hyperkalemia | Yes (class effect) | Yes (class effect) |
| Hypotension | Yes (especially first dose) | Yes (less pronounced) |
| Fetal toxicity | Contraindicated in pregnancy | Contraindicated in pregnancy |
| Cost (generic) | $4–$15/month | $10–$30/month |
| Evidence base | Extensive (30+ years of trials) | Strong (20+ years of trials) |
| Guideline preference | First-line for most indications | Preferred when ACE inhibitor not tolerated |
Clinical Evidence: Are They Equivalent?
For most indications, ACE inhibitors and ARBs produce similar clinical outcomes. The ONTARGET trial (2008) directly compared ramipril (ACE inhibitor) vs. telmisartan (ARB) in 25,620 high-risk patients and found no significant difference in the primary cardiovascular endpoint. Both drugs reduced cardiovascular events to the same degree.
However, ACE inhibitors have more extensive evidence in specific populations:
- Heart failure with reduced ejection fraction (HFrEF) — ACE inhibitors have the most robust evidence (CONSENSUS, SOLVD, SAVE trials). ARBs are an acceptable alternative (CHARM-Alternative trial) but are generally second-line.
- Post-MI — ACE inhibitors (captopril, [lisinopril](/drugs/lisinopril), ramipril) have the strongest evidence. ARBs are used when ACE inhibitors are not tolerated.
- Diabetic nephropathy — Both classes reduce proteinuria and slow CKD progression. ACE inhibitors have more data in type 1 diabetes; ARBs have more data in [type 2 diabetes](/conditions/type-2-diabetes) (RENAAL, IDNT trials).
When to Use an ARB Instead of an ACE Inhibitor
| Situation | Recommendation |
|---|---|
| ACE inhibitor cough | Switch to ARB — will not cause cough |
| ACE inhibitor angioedema | Switch to ARB — much lower risk (not zero) |
| Asian patient (high cough risk) | Consider starting with ARB |
| Black patient (higher angioedema risk) | Consider starting with ARB or calcium channel blocker |
| Diabetic nephropathy (type 2) | ARBs have strong evidence (RENAAL, IDNT) |
| Heart failure: cannot tolerate ACE inhibitor | ARB (candesartan, valsartan) — CHARM-Alternative |
What About Combining ACE Inhibitors and ARBs?
Combining an ACE inhibitor with an ARB (dual RAAS blockade) was once thought to provide additive benefit. The ONTARGET trial definitively showed that combination therapy increases the risk of hypotension, acute kidney injury, and hyperkalemia without reducing cardiovascular events. Dual RAAS blockade is contraindicated in most patients. The only exception is the combination of ACE inhibitor + sacubitril/valsartan (Entresto) in HFrEF, which requires a 36-hour washout period between the ACE inhibitor and sacubitril.
Cost Comparison
ACE inhibitors are generally less expensive than ARBs. Generic lisinopril costs $4–$10/month; generic [losartan](/drugs/losartan) costs $10–$20/month. Both are on virtually every insurance formulary at low cost. See our lisinopril cost guide and losartan cost guide for current pricing.
References
- Yusuf S, et al. Telmisartan, ramipril, or both in patients at high risk for vascular events (ONTARGET). N Engl J Med. 2008;358(15):1547-1559.
- Granger CB, et al. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function (CHARM-Alternative). Lancet. 2003;362(9386):772-776.
- Brenner BM, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy (RENAAL). N Engl J Med. 2001;345(12):861-869.
Save up to 80% on this medication
Use a free RxGo discount card at 67,000+ pharmacies — no sign-up, no insurance needed.
About the Author
James Okafor, RPh, MBA
Registered Pharmacist & Health Economics Writer
James Okafor is a registered pharmacist with over 12 years of experience in retail and clinical pharmacy settings. He holds an MBA with a focus on healthcare management and specializes in translating complex drug pricing, formulary, and insurance coverage topics into clear, actionable guidance for patients. Before joining RxGuide, James worked as a clinical pharmacist at a regional hospital system and as a pharmacy benefits consultant for a national PBM. His writing focuses on cost transparency, generic alternatives, and helping patients navigate the U.S. prescription drug system.
View full profile on our Editorial Team page →Get the RxGo app — free prescription discounts on the go
Works at 67,000+ pharmacies · No membership needed