A 58-year-old man with chronic heart failure (LVEF 35%) is on lisinopril, metoprolol, and spironolactone. He develops worsening dyspnea and orthopnea. All of the following drugs would be appropriate additions to his regimen EXCEPT:

Question

Accepted Answer

D. Ivabradine — to reduce heart rate in sinus rhythm if HR remains elevated. ## Pharmacological Management of Systolic Heart Failure: Drug Selection

### The Inappropriate Choice: Ivabradine

**Key Point:** Ivabradine is indicated ONLY in patients with:
1. Systolic heart failure (HFrEF)
2. **Sinus rhythm** (not atrial fibrillation)
3. Heart rate ≥70 bpm despite optimal beta-blocker therapy
4. No hypotension or bradycardia

In this case, the patient is already on metoprolol (a beta-blocker), which is the first-line agent for heart rate control in HFrEF. Ivabradine is a second-line option only if heart rate remains uncontrolled (≥70 bpm) on maximally tolerated beta-blocker doses. The stem does not specify elevated heart rate, making ivabradine's addition unjustified without that clinical trigger.

### Why the Other Drugs Are Appropriate

| Drug | Mechanism | Evidence | Class |
|------|-----------|----------|-------|
| **ARNI (Sacubitril/valsartan)** | Neprilysin inhibitor + ARB; replaces ACE-I/ARB | PARADIGM-HF: 27% mortality ↓ vs enalapril | I |
| **Digoxin** | Positive inotrope + vagomimetic; reduces symptoms, hospitalisation (not mortality) | DIG trial; especially useful with AF | IIb (HFrEF + AF) |
| **SGLT2 inhibitor** | Improves cardiac remodelling, reduces congestion, enhances natriuresis | DAPA-HF, EMPEROR-Reduced: mortality/HF hospitalisation ↓ | I (all HFrEF) |

### Clinical Pearl
**High-Yield:** Modern HFrEF management follows the "quadruple therapy" paradigm:
1. **ACE-I/ARB/ARNI** (or ARNI alone)
2. **Beta-blocker**
3. **MRA** (spironolactone, eplerenone)
4. **SGLT2 inhibitor**

Ivabradine is a **fifth-line agent** for rate control if heart rate remains ≥70 bpm on optimal beta-blockade.

**Mnemonic:** **ARNI-SGLT2-BB-MRA** = modern quadruple therapy for HFrEF. Ivabradine is only added if **HR uncontrolled on BB**.

[cite:Harrison 21e Ch 281; ESC HF Guidelines 2021]

Answer

A. Sacubitril/valsartan (ARNI) — can replace the ACE inhibitor

Answer

B. Digoxin — to improve contractility and reduce hospitalisation in HFrEF with AF

Answer

C. SGLT2 inhibitor (e.g., dapagliflozin) — reduces mortality and hospitalisation regardless of diabetes status

A 58-year-old man with chronic heart failure (LVEF 35%) is on lisinopril, metoprolol, and spironolactone. He develops worsening dyspnea and orthopnea. All of the following drugs would be appropriate additions to his regimen EXCEPT:

Explanation

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