A 62-year-old woman with heart failure with reduced ejection fraction (HFrEF, LVEF 32%) and hypertension is intolerant to ACE inhibitors due to persistent dry cough. She is already on a beta-blocker and a diuretic. What is the preferred alternative to ACE inhibitor monotherapy in this scenario?

Explanation

## Rationale for ARB (Losartan) as ACE-I Alternative **Key Point:** Angiotensin II receptor blockers (ARBs) are the preferred alternative to ACE inhibitors in patients with ACE-I intolerance (cough, angioedema). ARBs provide equivalent mortality reduction without the troublesome side effects. **High-Yield:** ARBs block angiotensin II at the AT1 receptor, achieving the same neurohormonal blockade as ACE-I but without accumulation of bradykinin (the culprit behind ACE-I cough). Multiple trials (LOSARTAN, ELITE II, CHARM-Alternative) confirm non-inferiority or superiority of ARBs in HFrEF. ### ACE-I vs. ARB in HFrEF | Feature | ACE Inhibitor | ARB | |---|---|---| | **Mechanism** | Blocks ACE; ↓ Ang II; ↑ bradykinin | Blocks AT1 receptor; ↓ Ang II signaling | | **Mortality benefit** | ↓ 20–30% (SOLVD, CONSENSUS) | ↓ 20–30% (LOSARTAN, CHARM) | | **Cough** | 5–10% incidence | < 1% incidence | | **Angioedema** | 0.1–0.2% | 0.1–0.2% | | **First-line in HFrEF** | Yes | Yes (if ACE-I intolerant) | | **Hyperkalemia risk** | Moderate | Moderate (similar) | **Clinical Pearl:** Losartan, valsartan, and candesartan are all acceptable ARBs in HFrEF. Losartan is often chosen due to familiarity and cost, though valsartan has the most HFrEF-specific trial data (VALIANT). **Warning:** Do NOT combine ACE-I and ARB in the same patient (increased hyperkalemia and renal dysfunction risk without additional benefit). ## Why ARB is Superior to Other Options - **vs. Diltiazem:** Non-dihydropyridine calcium channel blockers (diltiazem, verapamil) are contraindicated in HFrEF with reduced ejection fraction due to negative inotropic effects and worsening of systolic dysfunction. - **vs. Increasing beta-blocker dose:** Beta-blockers alone do not replace the angiotensin-blocking effect of ACE-I or ARB. Both neurohormonal axes (catecholamine + renin-angiotensin) must be blocked for optimal outcomes. - **vs. Increasing diuretic dose:** Diuretics address volume overload but do not modify disease progression or reduce mortality. Increasing diuretics without adding an ACE-I or ARB equivalent is suboptimal therapy. [cite:Harrison 21e Ch 272]