Which agent has been shown to reduce mortality in patients with congestive heart failure?

Enalapril (Option B) is the Agent with Proven Mortality Reduction in Congestive Heart Failure

Enalapril is the correct answer, as ACE inhibitors have been definitively shown in multiple large randomized controlled trials to reduce mortality in patients with congestive heart failure across all severity levels. 1, 2, 3

Evidence for Mortality Reduction

ACE Inhibitors (Enalapril)

• The landmark CONSENSUS trial demonstrated that enalapril reduced 6-month mortality by 40% (26% vs 44%, P=0.002) and 1-year mortality by 31% in patients with severe heart failure (NYHA Class IV). 3
• The SOLVD-Treatment trial showed enalapril reduced all-cause mortality by 16% (35.2% vs 39.7%, P=0.0036) in patients with mild to moderate heart failure and ejection fractions ≤35%. 2
• The mortality benefit was primarily due to a 22% reduction in deaths from progressive heart failure, with the largest effect seen in preventing pump failure deaths rather than arrhythmic deaths. 2, 3
• ACE inhibitors are Class I, Level A recommendations for all patients with heart failure and reduced ejection fraction to reduce both morbidity and mortality. 1

Why Other Options Are Incorrect

Digitalis (Option A):

• The DIG trial showed digoxin has a neutral effect on all-cause mortality with no survival benefit. 1
• While digoxin reduced hospitalizations for worsening heart failure, it actually showed a significant 14% increase in cardiac deaths not due to progressive heart failure. 1
• Digoxin does not reduce mortality and should not be considered a mortality-reducing agent. 1

Furosemide (Option C):

• Loop diuretics are essential for symptom management and congestion relief but have never been shown to reduce mortality in heart failure trials. 1
• Diuretics remain standard therapy for fluid retention but lack mortality benefit data. 4

Procainamide (Option D):

• Sodium channel blockers (Class IA agents like procainamide) have been shown to increase mortality in post-myocardial infarction patients in the CAST study. 1
• Antiarrhythmic drugs that suppress ventricular arrhythmias do not translate into risk reduction and may be distinctly harmful. 1
• These agents should be viewed as providing no benefit and potentially being harmful for prophylactic treatment. 1

Clinical Implementation

Target Dosing for Enalapril

• Start at 2.5 mg twice daily in heart failure patients, particularly those at high risk for hypotension. 1, 5, 3
• Titrate gradually by doubling the dose at intervals of at least 2 weeks. 5
• Target dose is 10-20 mg twice daily, as used in mortality trials. 5
• Aim for target doses proven in clinical trials rather than just symptom control. 5

Monitoring Requirements

• Check renal function (creatinine) and serum potassium within 1-2 weeks of initiation and periodically thereafter. 5
• Monitor blood pressure at each dose adjustment. 5
• Asymptomatic hypotension does not require dose reduction or discontinuation. 5

Additional Mortality-Reducing Therapies

While enalapril is the correct answer to this question, comprehensive heart failure management includes:

• Beta-blockers (carvedilol, metoprolol succinate, bisoprolol) reduce mortality by 34% with similar benefits for death and heart failure hospitalization. 1, 6
• Mineralocorticoid receptor antagonists reduce mortality and sudden cardiac death by 23% in patients already on ACE inhibitors and beta-blockers. 1
• Angiotensin receptor-neprilysin inhibitors (sacubitril/valsartan) showed 20% reduction in cardiovascular death or heart failure hospitalization compared to enalapril in the PARADIGM-HF trial. 1