What is the recommended dosage and management of Enalapril (Angiotensin-Converting Enzyme inhibitor) for patients with hypertension or heart failure?

Enalapril Dosing and Management for Hypertension and Heart Failure

For heart failure with reduced ejection fraction, start enalapril at 2.5 mg twice daily and titrate to the target dose of 10-20 mg twice daily as tolerated, with the goal of achieving at least 10 mg twice daily based on landmark mortality trials. 1

Heart Failure with Reduced Ejection Fraction (HFrEF)

Starting Dose and Titration Strategy

• Initial dose: 2.5 mg twice daily (or 2.5 mg once daily in older guidelines) 1, 2
• Target dose: 10-20 mg twice daily based on major mortality trials (CONSENSUS, V-HeFT II, SOLVD) 1
• Minimum effective dose: At least 50% of target (10 mg total daily) should be achieved when possible 1
• Titration schedule: Double the dose every 1-2 weeks as tolerated 1

The European Society of Cardiology guidelines emphasize that enalapril demonstrated a 30% relative risk reduction in death and 35% reduction in heart failure hospitalization when used at evidence-based doses 1. The mean daily doses actually achieved in the landmark trials ranged from 15.0 to 18.4 mg, underscoring that higher doses within the target range provide optimal benefit 1.

Pre-Treatment Considerations

• Consider withholding or reducing diuretics 24 hours before initiation to minimize first-dose hypotension, particularly in volume-depleted patients 1, 2
• Avoid potassium-sparing diuretics during initiation 1
• Discontinue NSAIDs and COX-2 inhibitors 1

Monitoring Protocol

• Check serum potassium and creatinine 5-7 days after starting and after each dose increase 1
• Recheck every 5-7 days until values stabilize 1
• Monitor blood pressure for at least 2 hours after first dose and until stable for an additional hour 1, 2
• Long-term monitoring at 3 months, then every 6 months 1

Acceptable Laboratory Changes

• Creatinine increase up to 50% above baseline or up to 3 mg/dL (266 μmol/L), whichever is greater, is acceptable 1
• Potassium up to 5.5-6.0 mmol/L may be tolerated 1
• Small increases in blood urea nitrogen and creatinine are expected and do not require discontinuation 1

Renal Impairment Adjustments

• Creatinine clearance >30 mL/min: Standard dosing (start 2.5 mg twice daily) 2
• Creatinine clearance ≤30 mL/min or serum creatinine ≥3 mg/dL: Start 2.5 mg once daily, maximum 40 mg daily 2
• Dialysis patients: 2.5 mg on dialysis days, adjust on non-dialysis days based on blood pressure response 2

Hypertension

Standard Dosing

• Initial dose: 5 mg once daily for patients not on diuretics 2
• Initial dose: 2.5 mg once daily for patients currently on diuretics, with medical supervision for at least 2 hours 2
• Usual maintenance range: 10-40 mg daily, given once daily or in two divided doses 2, 3
• If once-daily dosing loses efficacy toward end of interval, consider twice-daily administration or dose increase 2

The SCOPE-AS trial demonstrated that gradual titration of enalapril from 2.5 mg twice daily to 10 mg twice daily was well tolerated even in patients with symptomatic severe aortic stenosis, supporting its safety profile when properly titrated 1.

Critical Management Pitfalls

Hypotension Management

• Asymptomatic hypotension does not require treatment adjustment 1
• For symptomatic hypotension: Review and reduce non-essential vasodilators (nitrates, calcium channel blockers), reduce diuretic dose if no congestion present 1
• First-dose hypotension does not preclude careful subsequent titration 2

When to Stop or Reduce Dose

• Substantial renal function deterioration beyond acceptable parameters 1
• Persistent hyperkalemia >6.0 mmol/L despite stopping potassium supplements and potassium-sparing diuretics 1
• Symptomatic hypotension unresponsive to diuretic reduction 1

Absolute Contraindications

• Bilateral renal artery stenosis 1
• History of angioedema with any ACE inhibitor 1
• Current angioedema 1

Combination Therapy

• Always combine with beta-blockers and mineralocorticoid receptor antagonists in HFrEF 1
• Diuretics should be added for volume management but always in combination with ACE inhibitors, never alone 1
• Avoid combining with potassium supplements or potassium-sparing diuretics during initiation 1, 2

Alternative Considerations

If cough develops and is proven due to enalapril (recurs after withdrawal and rechallenge), substitute with an angiotensin receptor blocker 1. However, extreme caution is warranted as angioedema can also occur with ARBs in patients who experienced it with ACE inhibitors 1.