Every week someone asks a fair question: with new heart failure drugs around, do ACE inhibitors still matter for left ventricular dysfunction? Short answer: yes. They reduce death, cut hospitalizations, and slow remodeling. They sit at the core of therapy, side-by-side with beta-blockers, MRAs, SGLT2 inhibitors, and in many cases ARNIs. Here’s exactly where they fit, how to use them, and when to switch or hold.

TL;DR / Key takeaways

- Yes, ACE inhibitors still matter in 2025 for left ventricular (LV) dysfunction. Landmark trials (CONSENSUS 1987; SOLVD 1991/1992; SAVE 1992; AIRE 1993) showed meaningful reductions in mortality and heart failure hospitalizations.
- Indications: symptomatic HFrEF (EF ≤40%), asymptomatic LV dysfunction (Stage B, post-MI or other causes), and post-MI LV dysfunction early after stabilization. They improve survival, limit remodeling, and delay progression.
- ARNIs (sacubitril/valsartan) are preferred for symptomatic HFrEF when tolerated (PARADIGM-HF). But ACEI remain first-line if ARNI isn’t available, not tolerated, or cost-limited-and still a go-to early post-MI (PARADISE-MI showed no clear win over ramipril for the primary endpoint).
- How to use: start low, titrate every 1-2 weeks to target doses, check creatinine and potassium at baseline and after each up-titration. Expect a small bump in creatinine; back off if creatinine rises >30% from baseline or K+ >5.5 mmol/L.
- Avoid in pregnancy, history of angioedema, bilateral renal artery stenosis, or severe hyperkalemia. Watch the "triple whammy": ACEI + diuretic + NSAID.

How to use ACE inhibitors in LV dysfunction (step-by-step)

Here’s the practical, clinic-ready way to start and titrate ACE inhibitors for LV dysfunction while keeping patients safe.

1) Confirm the indication and clinical context

• Symptomatic HFrEF (EF ≤40%): initiate ACEI unless you’re starting ARNI de novo. If already on ACEI and stable, consider switch to ARNI later.
• Asymptomatic LV dysfunction (Stage B), including post-MI EF ≤40%: start ACEI once hemodynamically stable. This slows progression to symptomatic heart failure and improves outcomes.
• Borderline EF (41-49%): less robust evidence; ACEI may help if there’s prior MI, hypertension with LV hypertrophy, or remodeling on imaging.
• HFpEF: ACEI can help with blood pressure and afterload but haven’t shown clear mortality benefit in HFpEF.

2) Check baseline safety

• Blood pressure: systolic ≥95-100 mmHg is a workable floor for careful initiation.
• Renal function and electrolytes: record creatinine/eGFR and K+. ACEI are fine in mild-to-moderate CKD, but you need a plan to monitor.
• Contraindications: pregnancy, history of angioedema with ACEI, bilateral renal artery stenosis, K+ ≥5.5 mmol/L, or prior life-threatening hyperkalemia on RAAS blockade.
• Drug interactions: NSAIDs increase AKI risk; potassium supplements and potassium-sparing agents (including high-dose spironolactone/eplerenone) raise K+; lithium levels can rise.

3) Start low and go slow (but go)

1. Choose an ACEI you can titrate to target (see dosing table below). Enalapril, lisinopril, captopril, ramipril, perindopril, quinapril, and trandolapril all have HF evidence or guideline support.
2. Start at a low dose, usually at night if blood pressure is soft, and warn about transient dizziness.
3. Add or maintain a loop diuretic if there’s congestion. Don’t chase target doses at the expense of congestion control.

4) Titrate to target or max tolerated

• Up-titrate every 1-2 weeks (longer if frail or BP is borderline) aiming for trial-proven targets.
• Check creatinine and K+ 1-2 weeks after initiation and after each dose increase.
• Expect: mild creatinine rise (≤30% from baseline) and small K+ bump. That’s the hemodynamic effect and often acceptable.

5) What to do with abnormal labs

• Creatinine rise ≤30% from baseline: continue; recheck in 1-2 weeks.
• Creatinine rise >30% or symptomatic hypotension: halve the dose or step back to prior dose; review diuretics, volume status, and NSAIDs.
• Potassium 5.5-6.0 mmol/L: pause potassium supplements, review diet, consider adding a potassium binder if needed; reduce dose or hold ACEI until K+ <5.5.
• Potassium >6.0 mmol/L or EKG changes: treat hyperkalemia urgently and hold ACEI; restart later at a lower dose once safe, if appropriate.

6) Side effects and switches

• Cough (dry, persistent): common; not dangerous. If it annoys the patient, switch to an ARB.
• Angioedema: rare but serious. Stop immediately and avoid all ACEI for life. Most patients can use an ARB later under close monitoring; avoid sacubitril/valsartan after ACEI-related angioedema.
• Dizziness or fatigue: check volume status and other meds. Sometimes splitting doses or taking at night helps.

7) ACEI vs ARNI vs ARB - the quick navigation

• HFrEF, symptomatic: if you can, start ARNI de novo. If not, start ACEI now-don’t delay proven therapy-and consider switch to ARNI once stable.
• Post-MI with LV dysfunction: ACEI remains standard starter; PARADISE-MI didn’t prove ARNI superiority over ramipril for the primary endpoint.
• If ACEI cough or angioedema: use an ARB (losartan, valsartan, candesartan). ARB is also reasonable if ACEI is not tolerated for BP or lab reasons.

8) The 36-hour rule

• Switching ACEI → ARNI: stop ACEI, wait 36 hours, then start ARNI to reduce angioedema risk.
• Switching ARNI → ACEI: same 36-hour washout applies.

A simple decision path

• If HFrEF and stable BP: start ARNI or ACEI today → add beta-blocker (or continue) → add MRA → add SGLT2 inhibitor → diuretics for symptoms → up-titrate to target.
• If post-MI with LV dysfunction: start ACEI once stable → add beta-blocker → add MRA if EF ≤40% and no contraindication → consider SGLT2 inhibitor for cardiometabolic benefit.
• If cough on ACEI: switch to ARB; consider ARNI if criteria met and no history of angioedema.
• If K+ drift is a pattern: coach on diet, stop K+ supplements, check hidden sources (salt substitutes), consider potassium binders, and keep the RAAS therapy if safe.

Real-world examples, dosing table, and decision aids

Examples from clinic

• Newly diagnosed HFrEF (EF 30%), BP 118/72, eGFR 64, K+ 4.6: start enalapril 2.5 mg BID, metoprolol succinate 12.5-25 mg daily, dapagliflozin 10 mg daily; add spironolactone 12.5-25 mg if K+ stable. Recheck labs in 1-2 weeks; titrate enalapril to 10-20 mg BID over a few weeks.
• Post-MI EF 35% two days after PCI, BP 102/66, eGFR 52: start lisinopril 2.5-5 mg nightly, carefully add beta-blocker, then MRA if K+ allows. Keep diuretics minimal to maintain perfusion. Consider ARNI later once past the early post-MI phase if symptoms persist.
• CKD stage 3b, EF 38%, K+ 4.9: start low-dose ACEI and SGLT2 inhibitor; watch potassium weekly early on. If K+ creeps to 5.5, adjust diet, trim MRA dose, or add a potassium binder to preserve the survival benefit of RAAS blockade.

Common ACE inhibitors and HF dosing targets

What benefits can you quote at the bedside?

Modern guidelines (AHA/ACC/HFSA 2022; ESC 2021 with 2023 update) still place ACEI at the foundation of therapy for LV dysfunction, with ARNIs preferred in symptomatic HFrEF when feasible.

Heuristics I use in clinic

• If BP is soft, pick a short-acting ACEI (like captopril) for the first days; switch to a longer-acting agent once stable.
• Don’t let a small creatinine rise scare you; the mortality benefit typically outweighs a modest bump.
• If K+ inches up, fix diet and hidden sources first, then consider a binder to preserve life-prolonging meds.
• Get to target doses gently but relentlessly; schedule follow-ups before the patient leaves.

Checklists, mini-FAQ, and next steps

Pre-start checklist

• BP ≥95-100 mmHg and no shock or decompensation.
• Creatinine/eGFR and K+ checked and documented.
• No pregnancy, no history of ACEI angioedema, no bilateral renal artery stenosis.
• Review meds: NSAIDs, K+ supplements, potassium-sparing diuretics, lithium.
• Patient counseling: cough possibility, dizziness, lab checks in 1-2 weeks, call if facial swelling or severe lightheadedness.

Titration checklist

• Increase dose every 1-2 weeks if BP and labs allow.
• Recheck creatinine and K+ after each change.
• Watch for rising K+, lightheadedness, or worsening kidney function; adjust diuretics and dietary K+ first.
• Document the target dose and the plan to reach it.

Sick day rules

• If vomiting, diarrhea, or poor oral intake: hold ACEI and diuretics for 24-48 hours; restart when eating/drinking normally.
• Skip NSAIDs; use alternatives for pain.

Mini-FAQ

• Are ACEI still needed if we have ARNIs? Yes. ARNIs are preferred for symptomatic HFrEF, but ACEI are the next-best option and remain first-line early post-MI and in asymptomatic LV dysfunction.
• How soon after MI? Start once the patient is hemodynamically stable, usually within 24 hours. Trials like SAVE and AIRE support early initiation in LV dysfunction.
• What creatinine rise is acceptable? Up to 30% from baseline is common and usually acceptable. Beyond that, reassess dose, volume status, and nephrotoxin use.
• What about cough? If persistent and bothersome, switch to an ARB. The benefit is largely maintained.
• Angioedema risk? Rare (≈0.1-0.7%). Higher risk in Black patients and with prior angioedema. Stop immediately if swelling occurs.
• Use in CKD? Yes, but monitor closely. They slow CKD progression in many contexts and reduce HF events. Expect small creatinine and K+ rises.
• Pregnancy? Contraindicated. Use alternatives.
• HFpEF? No proven mortality benefit. Still useful for blood pressure control and afterload reduction.
• Can I combine ACEI with ARB or aliskiren? No to routine dual RAAS blockade; it increases kidney issues and hyperkalemia without clear outcome gains. Avoid aliskiren combination, especially in diabetes.
• How do SGLT2 inhibitors fit? They’re part of first-line HFrEF therapy; they play well with ACEI/ARNI, beta-blockers, and MRAs and don’t raise potassium.

Troubleshooting by scenario

• Low BP, dizzy, but congested: treat congestion first (diuretics), consider splitting ACEI dose or using shorter-acting agent temporarily; reassess other BP-lowering meds.
• Low BP, euvolemic, asymptomatic: you can still titrate slowly; aim for the highest tolerated dose rather than chasing a number.
• K+ 5.6-5.9 mmol/L, stable creatinine: stop supplements, check diet, consider starting a potassium binder to keep ACEI/MRA in place.
• Creatinine up 35% after starting: reduce ACEI dose or hold; review diuretics (overdiuresis?), stop NSAIDs, repeat labs in a week. Restart lower once stable.
• Persistent cough: switch to ARB; if HFrEF and appropriate, consider ARNI (with proper washout from ACEI).
• History of ACEI angioedema: avoid ACEI. Many can use ARBs cautiously later; avoid sacubitril/valsartan due to angioedema risk.

What the evidence and guidelines say (for your notes)

• CONSENSUS (1987 NEJM): Enalapril cut mortality in severe HF.
• SOLVD-Treatment (1991 NEJM): Enalapril reduced all-cause mortality and HF hospitalizations in symptomatic HFrEF.
• SOLVD-Prevention (1992 NEJM): Enalapril delayed onset of HF in asymptomatic LV dysfunction.
• SAVE (1992 NEJM): Captopril after MI with LV dysfunction reduced death and recurrent events.
• AIRE (1993 Lancet): Ramipril post-MI reduced mortality in patients with clinical HF.
• PARADIGM-HF (2014 NEJM): ARNI superior to enalapril for CV death or HF hospitalization in symptomatic HFrEF.
• PARADISE-MI (2021 NEJM): ARNI not superior to ramipril for the primary composite after MI in high-risk patients.
• Guidelines: AHA/ACC/HFSA 2022; ESC 2021 (2023 update) endorse ACEI as foundational therapy, with ARNIs preferred in symptomatic HFrEF when possible.

Next steps (what to do after reading this)

1. Identify patients with LV dysfunction (EF ≤40%) not on RAAS therapy and start or optimize ACEI now, unless ARNI is the better immediate choice.
2. Book labs and a titration visit in 1-2 weeks before the patient leaves.
3. Write down the target dose and an estimated timeline to reach it (usually 4-6 weeks).
4. Map interactions: stop NSAIDs, review potassium sources, and flag lithium for monitoring.
5. Educate the patient in plain language: why we’re using the drug, what side effects to watch for, and when to call.

This is bread-and-butter cardiology: keep it simple, be systematic, and don’t leave survival benefit on the table. Even in the age of ARNIs and SGLT2 inhibitors, a well-chosen ACE inhibitor, started right and titrated with intention, still changes the story for people living with LV dysfunction.