What is the role of Angiotensin-Converting Enzyme (ACE) inhibitors and beta blockers in the treatment of congestive heart failure?

Role of ACE Inhibitors and Beta Blockers in Congestive Heart Failure

ACE inhibitors and beta blockers should be used as first-line therapy in all patients with heart failure due to left ventricular systolic dysfunction (NYHA class I-IV), with ACE inhibitors initiated first, followed by beta blockers, both titrated to target doses used in clinical trials. 1

Evidence-Based Rationale

ACE Inhibitors

• Multiple randomized trials (CONSENSUS I, SOLVD-T) have conclusively shown that ACE inhibitors increase survival, reduce hospitalizations, and improve NYHA class and quality of life in all grades of symptomatic CHF 1
• ACE inhibitors have been shown to delay or prevent the development of symptomatic CHF in patients with asymptomatic left ventricular systolic dysfunction 1
• Higher doses of ACE inhibitors have been associated with greater reduction in the composite endpoint of death or hospitalization compared to lower doses (ATLAS trial) 1, 2

Beta Blockers

• Several major randomized controlled trials (USCP, CIBIS II, MERIT-HF, COPERNICUS) have conclusively demonstrated that beta blockers increase survival, reduce hospitalizations, and improve NYHA class and quality of life when added to standard therapy in patients with stable mild to moderate CHF 1
• The CAPRICORN study showed a reduction in mortality with carvedilol in post-myocardial infarction patients with reduced left ventricular systolic dysfunction 1
• Only three beta blockers (bisoprolol, carvedilol, and metoprolol CR/XL) have been proven to reduce mortality in heart failure 1

Implementation Algorithm

Step 1: Confirm Left Ventricular Systolic Dysfunction

• Echocardiography, radionuclide ventriculography, or radiological left ventricular angiography should be performed to confirm the presence of left ventricular systolic dysfunction 1

Step 2: Initiate ACE Inhibitor Therapy

• Start with a low dose and titrate gradually 1
• Recommended ACE inhibitors and dosing:

ACE Inhibitor	Starting dose (mg)	Target dose (mg)
Captopril	6.25 thrice daily	50-100 thrice daily
Enalapril	2.5 twice daily	10-20 twice daily
Lisinopril	2.5-5.0 once daily	30-35 once daily
Ramipril	2.5 once daily	5 twice daily or 10 once daily
Trandolapril	1.0 once daily	4 once daily

• Double dose at not less than 2-week intervals 1
• Monitor blood chemistry (urea, creatinine, K+) and blood pressure 1
• Remember: some ACE inhibitor is better than no ACE inhibitor 1

Step 3: Add Beta Blocker Therapy

• Initiate only after patient is stable on ACE inhibitor therapy 1
• Start with a low dose and titrate gradually 1
• Recommended beta blockers and dosing:

Beta Blocker	Starting dose (mg)	Target dose (mg)
Bisoprolol	1.25 once daily	10 once daily
Carvedilol	3.125 twice daily	25-50 twice daily
Metoprolol CR/XL	12.5-25 once daily	200 once daily

• Double dose at not less than 2-week intervals 1
• Monitor heart rate, blood pressure, and clinical status 1
• Remember: some beta blocker is better than no beta blocker 1

Special Considerations and Cautions

ACE Inhibitor Cautions

• Seek specialist advice for patients with:
  • Significant renal dysfunction (creatinine > 2.5 mg/dl or > 221 mmol/l) 1
  • Hyperkalaemia (> 5.0 mmol/l) 1
  • Symptomatic or severe asymptomatic hypotension (systolic BP < 90 mmHg) 1

Beta Blocker Cautions

• Seek specialist advice for patients with:
  • Severe (NYHA class IV) CHF 1
  • Current or recent (4 weeks) exacerbation of CHF 1
  • Heart block or heart rate < 60/min 1
  • Persisting signs of congestion (raised jugular venous pressure, ascites, marked peripheral edema) 1

Managing Common Issues

ACE Inhibitor-Related Issues

Cough

• Cough is common in CHF patients and may be due to pulmonary edema or underlying lung disease 1
• ACE inhibitor-induced cough rarely requires treatment discontinuation 1
• For troublesome cough proven to be due to ACE inhibition, consider substitution with an angiotensin receptor blocker 1

Worsening Renal Function

• Some increase in creatinine and potassium is expected and acceptable 1
• An increase in creatinine of up to 50% above baseline, or to 3 mg/dl, is acceptable 1
• If excessive rises occur, consider stopping nephrotoxic drugs (e.g., NSAIDs) and reducing diuretic dose if no congestion 1
• It is very rarely necessary to stop an ACE inhibitor; clinical deterioration is likely if treatment is withdrawn 1

Beta Blocker-Related Issues

• Temporary symptomatic deterioration may occur (in 20-30% of cases) during initiation/up-titration 1
• If symptomatic improvement occurs, it may develop slowly (3-6 months or longer) 1
• Patient education and close follow-up are essential during initiation and titration phases 1

Combination Therapy Benefits

• The combination of high-dose ACE inhibitors plus beta blockers plus digoxin has been associated with incrementally greater reductions in morbidity and mortality compared to low-dose ACE inhibitors alone 2
• The objective is to treat patients with both an ACE inhibitor and a beta blocker, both ideally given at the target doses used in large randomized trials 1