What medication should be added to the regimen of a patient with heart failure and hypertension who is already taking beta blockers, Angiotensin-Converting Enzyme (ACE) inhibitors, Angiotensin Receptor Blockers (ARB), and Spironolactone?

Ivabradine Should Be Added

For a patient with heart failure already on beta blockers, ACE inhibitors, ARB, and spironolactone, ivabradine (Option A) is the recommended addition if the patient remains symptomatic with a heart rate ≥70 bpm in sinus rhythm. 1, 2

Critical First Step: Identify the Problem

Before adding any medication, you must first address a major red flag in this regimen:

• The patient is taking BOTH an ACE inhibitor AND an ARB simultaneously with spironolactone—this triple combination is explicitly NOT recommended due to excessive risk of hyperkalemia and renal dysfunction 1
• One of these agents (either the ACE inhibitor or ARB) should be discontinued immediately 1

Rationale for Ivabradine

When to Add Ivabradine

Ivabradine is indicated for patients who meet ALL of the following criteria:

• LVEF ≤35% 1, 2, 3
• In sinus rhythm (not atrial fibrillation) 1, 2, 3
• Resting heart rate ≥70 bpm 1, 2, 3
• Persistently symptomatic (NYHA class II-IV) despite evidence-based beta-blocker dosing or maximally tolerated dose 1, 2, 3
• Already on optimized therapy with ACE inhibitor (or ARB), beta-blocker, and mineralocorticoid receptor antagonist 3, 4

Evidence Supporting Ivabradine

• The SHIFT trial demonstrated that ivabradine reduced the composite endpoint of hospitalization for worsening heart failure or cardiovascular death (hazard ratio 0.82,95% CI: 0.75-0.90, p<0.0001) 3
• This benefit was driven primarily by a 26% reduction in hospitalizations for worsening heart failure 3
• Ivabradine selectively inhibits the If current in the sinoatrial node, providing additional heart rate reduction beyond what beta-blockers achieve 1, 4

Why NOT the Other Options

Option B: Diltazem - CONTRAINDICATED

• Non-dihydropyridine calcium channel blockers (diltiazem, verapamil) are contraindicated in systolic heart failure 2, 5
• These agents have negative inotropic effects that worsen heart failure outcomes 5

Option C: Another Beta Blocker - NOT Indicated

• Only three beta-blockers have proven mortality benefit in heart failure: bisoprolol, carvedilol, and metoprolol CR/XL 1, 6
• The patient is already on a beta-blocker 1, 6
• Adding a second beta-blocker provides no additional benefit and increases risk of bradycardia and hypotension 1
• If the current beta-blocker is not one of the three evidence-based options, switch to one of these rather than adding another 1, 6

Option D: Another Calcium Channel Blocker - Avoid

• Calcium channel blockers (except amlodipine) should be avoided in heart failure with reduced systolic function 2, 5
• Even amlodipine is neutral at best and not recommended as add-on therapy for heart failure 5

Practical Implementation Algorithm

Step 1: Discontinue either the ACE inhibitor or ARB (keep only one) 1

Step 2: Verify the patient meets ivabradine criteria:

• Check rhythm (must be sinus rhythm, not atrial fibrillation) 2, 3
• Measure resting heart rate (must be ≥70 bpm) 1, 2, 3
• Confirm LVEF ≤35% 1, 2, 3
• Verify persistent symptoms despite optimized therapy 1, 2

Step 3: If criteria met, initiate ivabradine:

• Start at 5 mg twice daily 3
• Titrate to 7.5 mg twice daily or down to 2.5 mg twice daily to maintain heart rate 50-60 bpm 3
• Monitor for bradycardia, visual disturbances (phosphenes), and symptomatic improvement 3

Common Pitfalls to Avoid

• Do not add ivabradine if the patient has atrial fibrillation—it only works in sinus rhythm 1, 2, 3
• Do not add ivabradine if heart rate is <70 bpm—there is no benefit and increased risk of excessive bradycardia 1, 2, 3
• Do not continue the triple combination of ACE inhibitor + ARB + MRA—this significantly increases hyperkalemia risk 1
• Ensure the patient is on a maximally tolerated or target dose of an evidence-based beta-blocker before adding ivabradine 1, 2, 3

Alternative Consideration

If the patient does not meet criteria for ivabradine (e.g., heart rate <70 bpm, atrial fibrillation, or already well-controlled), consider:

• Switching the ARB to sacubitril/valsartan (ARNI) if the patient remains symptomatic on ACE inhibitor/ARB + beta-blocker + MRA 1
• This requires discontinuing the ACE inhibitor (with 36-hour washout) or ARB and provides additional mortality benefit 1