What medication should be added to a patient with heart failure with reduced ejection fraction (EF) and dilated cardiomyopathy, already on Valsartan (angiotensin II receptor antagonist), statin (HMG-CoA reductase inhibitor), metoprolol (beta-blocker), spironolactone (aldosterone antagonist), and furosemide (loop diuretic)?

Add Ivabradine (Option A)

For this patient with HFrEF on valsartan, metoprolol, spironolactone, and furosemide, ivabradine should be added if the patient remains symptomatic (NYHA Class II-IV), is in sinus rhythm, and has a resting heart rate ≥70 bpm despite being on metoprolol. 1

Rationale for Ivabradine

• Ivabradine is specifically indicated for symptomatic HFrEF patients with LVEF ≤35%, in sinus rhythm with heart rate ≥70 bpm, who remain symptomatic despite optimal medical therapy including beta-blockers. 1

• The 2016 ESC Guidelines recommend ivabradine (Class IIa, Level B) to reduce HF hospitalization and cardiovascular death in patients already on evidence-based beta-blocker doses or maximally tolerated doses. 1

• The 2021 ACC Expert Consensus reinforces ivabradine use (Class IIa, Level B-R) for patients with LVEF ≤35% on maximally tolerated beta-blocker with resting heart rate >70 bpm. 1

• Clinical benefit is most pronounced when baseline heart rate is ≥75 bpm, where ivabradine reduces cardiovascular mortality by 17%, HF mortality by 39%, and HF hospitalization by 30%. 2

• Ivabradine provides pure heart rate reduction without negative inotropic or blood pressure-lowering effects, unlike increasing beta-blocker doses. 2, 3

Why NOT the Other Options

Bisoprolol (Option B) - Incorrect

• The patient is already on metoprolol, one of the three evidence-based beta-blockers (bisoprolol, carvedilol, sustained-release metoprolol succinate) proven to reduce mortality in HFrEF. 1

• Switching between beta-blockers is not recommended when the patient is already on an appropriate agent; the focus should be on optimizing the current beta-blocker dose first. 1

• Adding a second beta-blocker would be inappropriate and potentially harmful due to excessive bradycardia and hypotension risk.

Verapamil (Option C) - Contraindicated

• Calcium channel blockers with negative inotropic effects are explicitly contraindicated in HFrEF patients. 1

• Both ACC/AHA and ESC Guidelines state that diltiazem and verapamil are NOT recommended (Class III) as they increase the risk of HF worsening and HF hospitalization. 1

• Verapamil can precipitate acute decompensation in patients with reduced ejection fraction. 1

Diltiazem (Option D) - Contraindicated

• Diltiazem carries the same contraindication as verapamil in HFrEF patients due to negative inotropic effects. 1

• ESC Guidelines explicitly state (Class III, Level C) that diltiazem or verapamil are not recommended in HFrEF as they increase risk of HF worsening and hospitalization. 1

Critical Implementation Points

Before adding ivabradine, verify:

• Patient is in sinus rhythm - ivabradine is only indicated for sinus rhythm, not for persistent/chronic atrial fibrillation (though history of paroxysmal AF is not a contraindication). 1, 4

• Resting heart rate is ≥70 bpm (ideally ≥75 bpm for maximum benefit). 1, 2

• Metoprolol is at maximally tolerated dose - beta-blocker optimization should be attempted first. 1

• Patient remains symptomatic (NYHA Class II-IV) despite current therapy. 1

Dosing strategy:

• Start ivabradine 5 mg twice daily, then titrate to 7.5 mg twice daily or down to 2.5 mg twice daily to maintain heart rate between 50-60 bpm. 4, 5

• Target heart rate of 50-60 bpm is associated with the lowest event rates. 5

Common pitfalls to avoid:

• Do not use ivabradine if patient has chronic/persistent atrial fibrillation or is 100% atrially paced. 1, 4

• Monitor for bradycardia (most common adverse effect) and transient visual disturbances (phosphenes). 4, 3

• Do not discontinue or reduce beta-blocker when adding ivabradine - they work synergistically. 1, 6