What is the best management approach for a patient with left ventricular dysfunction who is already on long-term Angiotensin-Converting Enzyme (ACE) inhibitor therapy?

Management of Left Ventricular Dysfunction on Long-Term ACE Inhibitor Therapy

For patients with left ventricular dysfunction already on long-term ACE inhibitor therapy, the ACE inhibitor should be continued indefinitely and optimized to target doses proven in clinical trials, while adding beta-blockers, mineralocorticoid receptor antagonists, and SGLT2 inhibitors as foundational therapies to reduce mortality and hospitalizations. 1

Continue and Optimize ACE Inhibitor Therapy

ACE inhibitors should never be discontinued in patients with left ventricular systolic dysfunction, as clinical deterioration is likely if treatment is withdrawn. 2 The evidence is unequivocal that ACE inhibitors improve survival, reduce hospitalizations, and improve symptoms in patients with heart failure due to left ventricular systolic dysfunction across all NYHA functional classes (I-IV). 3

Target Dose Titration

If your patient is not already at target doses, aggressive up-titration is essential. 3, 1 The following target doses have proven mortality benefit:

• Enalapril: 2.5 mg BID initially → target 10-20 mg BID 3, 4
• Lisinopril: 2.5-5.0 mg daily initially → target 30-35 mg daily 3
• Ramipril: 2.5 mg daily initially → target 5 mg BID or 10 mg daily 3
• Captopril: 6.25 mg TID initially → target 50-100 mg TID 3, 4

Critical pitfall: Many clinicians titrate ACE inhibitors based on symptomatic improvement alone, but guidelines explicitly state titration should target the doses used in clinical trials, not symptom resolution. 3

Add Beta-Blocker Therapy

Beta-blockers are first-line therapy alongside ACE inhibitors for all patients with left ventricular systolic dysfunction (NYHA class I-IV), not second-line therapy. 2, 1 Multiple randomized controlled trials (CIBIS II, MERIT-HF, COPERNICUS) conclusively demonstrated that beta-blockers increase survival, reduce hospital admissions, and improve NYHA class and quality of life when added to ACE inhibitors. 2

Specific Beta-Blocker Selection

Only three beta-blockers have proven mortality reduction—benefits cannot be assumed as a class effect: bisoprolol, carvedilol, and metoprolol succinate extended-release. 2, 1 Use a "start-low, go-slow" approach with careful monitoring of heart rate, blood pressure, and clinical status after each dose titration. 2

Common error: Avoiding beta-blockers in older adults or patients with peripheral vascular disease, erectile dysfunction, diabetes, interstitial pulmonary disease, or irreversible COPD—these are NOT contraindications. 2

Add Mineralocorticoid Receptor Antagonists (MRAs)

Add spironolactone or eplerenone if the patient remains symptomatic (NYHA class II-IV) despite ACE inhibitor and beta-blocker therapy. 1 This requires close monitoring of potassium levels and renal function. 2

Add SGLT2 Inhibitors

SGLT2 inhibitors should be initiated as part of foundational therapy in all patients with HFrEF, regardless of diabetes status. 1 Recent evidence supports initiating all four foundational medication classes (ACE inhibitor/ARB/ARNI, beta-blocker, MRA, SGLT2 inhibitor) simultaneously with rapid up-titration within 1 month, rather than the older sequential approach. 1

Special consideration: In patients with persistent low blood pressure (SBP <90 mmHg) who are asymptomatic or mildly symptomatic with adequate perfusion, start SGLT2 inhibitors and MRAs first (least blood pressure effect), as they have rapid beneficial effects. 1

Monitoring Parameters

Monitor renal function and potassium before initiation, 1-2 weeks after each dose increment, and at 3-6 month intervals. 3

Acceptable Laboratory Changes on ACE Inhibitors

• Creatinine increase up to 50% above baseline or to 3 mg/dL (266 μmol/L), whichever is greater, is acceptable 2
• Potassium up to 6.0 mmol/L is acceptable 2

When to Adjust Therapy

If creatinine or potassium rises excessively despite these thresholds:

1. Stop nephrotoxic drugs (NSAIDs) 2
2. Discontinue non-essential vasodilators (calcium antagonists, nitrates) 2
3. Stop potassium supplements and potassium-retaining agents (triamterene, amiloride) 2
4. If no signs of congestion, reduce diuretic dose 2
5. If changes persist, halve the ACE inhibitor dose and recheck blood chemistry 2
6. Seek specialist advice if K rises to 6.0 mmol/L or creatinine increases by 100% or to above 4 mg/dL (354 μmol/L) 2

When to Consider ARBs

ARBs are NOT first-line therapy and should only be used if ACE inhibitor adverse effects are intolerable (intractable cough or angioedema). 2, 3, 1 The evidence base for ACE inhibitors is stronger than for ARBs. 2

Critical error: Routinely combining ACE inhibitors and ARBs increases the risk of hyperkalemia and renal insufficiency without clear mortality benefit. 2, 5 This combination should be avoided. 5

Diuretic Management

Add diuretics as needed for fluid overload to reduce symptoms and hospitalizations. 1 However, diuretics are NOT considered foundational therapy because they do not reduce mortality. 1 Loop diuretics (furosemide, bumetanide) are preferred over thiazides in patients with significant renal impairment (GFR <30-40 mL/min). 2, 4

Long-Term Continuation

ACE inhibitors must be continued indefinitely in patients with left ventricular dysfunction. 6, 7 Even in patients whose ejection fraction normalizes after acute myocarditis, discontinuing ACE inhibitors results in higher incidence of recurrent heart failure (33% vs 5%) and lower ejection fraction (47% vs 57%). 7