Which class of drugs reduces mortality in HFrEF by inhibiting the RAAS system and is often started first?

• A. Calcium channel blockers.
• B. Digoxin.
• C. ACE inhibitors (or ARBs if ACE inhibitors not tolerated).
• D. Diuretics.

Answer: (C)

Blocking the RAAS with ACE inhibitors (and ARBs if ACE inhibitors aren’t tolerated) reduces mortality in heart failure with reduced ejection fraction by dampening the neurohormonal cascade that drives vasoconstriction, sodium and fluid retention, and adverse ventricular remodeling. By inhibiting the formation or effects of angiotensin II, these drugs decrease afterload, lessen preload, and slow the progression of remodeling, which translates into longer survival and fewer deaths. Because of this proven survival benefit, an ACE inhibitor is typically started early in HFrEF when blood pressure, kidney function, and potassium levels permit, often as a first disease-modifying step. If a patient cannot tolerate ACE inhibitors due to cough or angioedema, an ARB provides comparable mortality benefit. Other options mainly address symptoms rather than survival: diuretics relieve congestion, digoxin can improve symptoms and may reduce hospitalizations but does not clearly reduce mortality, and certain calcium channel blockers do not improve survival in HFrEF.