ACEIs are the foundation of heart failure therapy. They have beneficial effects for both the symptomatic and asymptomatic patient with left ventricular dysfunction. They reduce mortality,⁴ decrease hospitalizations, enhance clinical status, and improve overall feeling of well-being.^5,6 Their mechanism and action are multifactorial. Initially, they were used as afterload-reducing agents. It is now known that ACEIs reduce myocardial volume and improve ejection fraction by left ventricular remodeling.^7,8 They also reduce norepinephrine levels⁹ and enhance the action of kinins.¹⁰ ACEIs should be started at a low dose and titrated upward as tolerated. Aspirin therapy may attenuate the benefit of ACEIs by blocking the effects of kinin-mediated prostaglandin synthesis.¹¹ ACEI use is contraindicated in patients with angioedema and anuric renal failure. They must be used very cautiously in patients who are hypotensive (blood pressure <80 mm Hg), hyponatremic, or hyperkalemic or whose serum creatinine is greater than 3.0 μ/mL.¹²

Beta-blockers are now included as first-line therapy in all patients with mild to moderate heart failure. These patients maintain an overstimulated sympathetic nervous system, resulting in high levels of circulating serum norepinephrine. Chronic stimulation results in myocyte necrosis, peripheral vasoconstriction,¹³ cardiac hypertrophy, left ventricular dysfunction, and ventricular arrhythmias. These deleterious effects ultimately result in an increase in cardiac death. Beta-blockers produce a significant dose-dependent mortality and morbidity benefit. They reduce the risk of rehospitalization and lower the instance of sudden cardiac death and death from progressive heart failure.^14,15

Beta-blockers should be started in low doses and titrated upward slowly. Acute decompensation can occur when starting beta-blockers, so patients should be euvolemic and already on a stable dose of ACEI. Specific target doses are as follows: metoprolol CR/XL 200 mg daily, bisoprolol 5 mg daily, and carvedilol 25 mg twice a day.^16,17 Titration should be stopped if a patient’s heart rate is less than 55 beats/minute or systolic blood pressure is less than 85 mm Hg. It may take up to 3 months to see a significant clinical response from beta-blocker therapy. Patients with clinically unstable heart failure are often dependent on adrenergic stimulation and can decompensate when started on beta-blockers. In patients hospitalized for decompensated heart failure, the posthospitalization goal should be to maintain or resume their previous beta-blocker dose. A withdrawal or reduction of beta-blocker therapy may result in increased mortality.