What is the recommended treatment regimen for patients with hypertension or heart failure using Angiotensin-Converting Enzyme (ACE) inhibitors?

ACE Inhibitors for Hypertension and Heart Failure Management

ACE inhibitors are recommended as first-line therapy for patients with heart failure with reduced ejection fraction (HFrEF) and hypertension, with specific target doses established in clinical trials to reduce morbidity and mortality. 1

Indications and Benefits

• ACE inhibitors are indicated for:

  • Heart failure with reduced ejection fraction (LVEF ≤40%)
  • Hypertension management
  • Post-myocardial infarction with LV systolic dysfunction

• Benefits include:

  • Decreased morbidity and mortality in HFrEF 1
  • Reduced hospitalizations for heart failure 1
  • Improved NYHA functional class and quality of life 1
  • Prevention of HF in high-risk cardiovascular patients 2

Recommended ACE Inhibitors and Dosing

ACE Inhibitor	Starting Dose	Target Dose
Captopril	6.25 mg three times daily	50-100 mg three times daily
Enalapril	2.5 mg twice daily	10-20 mg twice daily
Lisinopril	2.5-5.0 mg once daily	20-40 mg once daily
Ramipril	2.5 mg once daily	5 mg twice daily or 10 mg once daily
Trandolapril	1.0 mg once daily	4 mg once daily

Titration Protocol

1. Start with low dose (see table above) 1, 3
2. Double dose at 2-week intervals 1, 3
3. Aim for target doses used in clinical trials 2
4. Monitor blood chemistry (urea, creatinine, K+) and blood pressure at each titration step 1, 3

Monitoring Parameters

• Before starting treatment
• 1-2 weeks after each dose increment
• At 3-6 month intervals once on stable dose
• When adding medications that affect renal function
• More frequent monitoring for patients with renal dysfunction 3

Common Side Effects and Management

Hypotension

• Asymptomatic hypotension generally requires no intervention 1, 3
• For symptomatic hypotension:
  • Consider reducing diuretic dose if no signs of congestion
  • Reduce doses of other vasodilators (nitrates, calcium channel blockers)

Renal Function Changes

• Small increases in creatinine are expected and acceptable
• An increase in creatinine of up to 50% above baseline or to 3 mg/dL (266 μmol/L) is acceptable 1
• If greater increases occur:
  • Stop nephrotoxic drugs (NSAIDs)
  • Consider reducing diuretic dose if no congestion
  • If persistent, halve ACE inhibitor dose and recheck

Hyperkalemia

• Monitor potassium levels regularly
• If K+ >5.7 mEq/L:
  • Reduce/stop potassium supplements and potassium-sparing diuretics
  • Consider reducing ACE inhibitor dose if persistent 1, 4

Cough

• Occurs in up to 20% of patients 3, 5
• If troublesome and proven to be due to ACE inhibitor:
  • Consider switching to an ARB 1

Alternative Therapies

• If ACE inhibitors are not tolerated:

  • ARBs are recommended as alternative first-line therapy 1
  • ARBs have similar efficacy but don't cause cough 1
  • Meta-analysis shows ACE inhibitors reduce mortality by 11% while ARBs have no significant mortality benefit 6

• For patients who remain symptomatic despite optimal therapy:

  • Consider ARNI (Angiotensin Receptor-Neprilysin Inhibitor) 1
  • Start at 24/26mg twice daily and titrate to 97/103mg twice daily 3

Special Considerations

• Renal artery stenosis: Monitor renal function closely; increases in BUN and creatinine observed in 20% of patients 4
• Pregnancy: Contraindicated due to risk of fetal harm
• Surgery: May cause hypotension during anesthesia; consider holding dose on day of surgery 4
• Angioedema: Discontinue immediately if it occurs 4, 5

Common Pitfalls to Avoid

• Failure to titrate to target doses used in clinical trials 2
• Premature discontinuation due to asymptomatic hypotension or small increases in creatinine 3
• Concurrent use of NSAIDs, which can reduce efficacy and increase risk of renal dysfunction 3
• Using non-dihydropyridine calcium channel blockers (diltiazem, verapamil) with ACE inhibitors in HFrEF 3
• Alpha-adrenergic blockers like doxazosin should be avoided in heart failure patients 1

By following these guidelines, ACE inhibitors can be effectively and safely used to reduce morbidity and mortality in patients with hypertension and heart failure.