What agent has been shown to reduce mortality in patients with congestive heart failure (CHF)?

Enalapril (ACE Inhibitor) Reduces Mortality in Congestive Heart Failure

The correct answer is B. Enalapril. ACE inhibitors, specifically enalapril, have been definitively shown to reduce mortality in patients with congestive heart failure across multiple landmark trials, making them foundational therapy for all patients with heart failure due to left ventricular systolic dysfunction unless contraindicated. 1, 2

Evidence for Mortality Reduction

ACE inhibitors are the only agents among the options listed with proven mortality benefit in heart failure:

• Enalapril reduced all-cause mortality by 16% (HR 0.84; 95% CI 0.76-0.93) and cardiovascular death by 20% (HR 0.80; 95% CI 0.71-0.89) in the landmark SOLVD-Treatment trial of 2,569 patients with symptomatic heart failure and ejection fraction ≤35%. 2

• Enalapril reduced hospitalization for heart failure by 30% in addition to its mortality benefit. 2

• In the CONSENSUS trial of NYHA Class IV heart failure patients, enalapril improved one-year survival to 64% compared to 48% with placebo. 2

• Even in asymptomatic patients with left ventricular dysfunction (SOLVD-Prevention trial), enalapril reduced first hospitalizations for heart failure by 32% and prevented progression to symptomatic heart failure in 32% of patients. 2

Why the Other Options Are Incorrect

Digitalis (Option A):

• Digitalis improves symptoms and hemodynamics but has never been shown to reduce mortality in heart failure. 1
• The FDA label for enalapril explicitly states that "the mortality benefit associated with enalapril does not appear to depend upon digitalis being present." 2
• Digitalis remains useful for symptom control and heart rate control in atrial fibrillation, but it is not a mortality-reducing agent. 1

Furosemide (Option C):

• Loop diuretics like furosemide are essential for managing congestion and improving symptoms, but their effect on mortality has never been demonstrated in clinical trials. 3
• Diuretics should be used in conjunction with ACE inhibitors and titrated according to clinical status, but they do not modify disease progression or survival. 1

Procainamide (Option D):

• Antiarrhythmic drugs like procainamide have no role in routine heart failure management and do not reduce mortality. 4
• In fact, most antiarrhythmic agents (except amiodarone) can depress left ventricular function and potentially worsen outcomes in heart failure patients. 4

Clinical Implementation

ACE inhibitors should be initiated in all patients with heart failure due to left ventricular systolic dysfunction (ejection fraction ≤40%) regardless of symptom severity:

• Start at low doses and up-titrate to target doses used in clinical trials to achieve adequate renin-angiotensin-aldosterone system inhibition. 1
• Target doses are critical—most patients in clinical practice receive suboptimal doses. 1
• ACE inhibitors are recommended as first-line therapy along with beta-blockers for all symptomatic patients (NYHA Class I-IV). 1
• For patients intolerant of ACE inhibitors due to cough or angioedema, angiotensin receptor blockers (ARBs) can be substituted, though the evidence base for mortality reduction is stronger for ACE inhibitors. 1

Important Caveats

Monitor renal function and potassium levels, particularly when combining ACE inhibitors with other RAAS antagonists like aldosterone antagonists (spironolactone), which also reduce mortality but increase hyperkalemia risk. 1

The mortality benefit of ACE inhibitors has been consistently demonstrated across multiple trials and represents one of the most important therapeutic advances in heart failure management over the past three decades. 1, 3