Which medication should be avoided in patients with Heart Failure with Reduced Ejection Fraction (HFrEF)?

Medications to Avoid in HFrEF

Diltiazem should be avoided in patients with HFrEF as it increases the risk of heart failure worsening and hospitalization due to its negative inotropic effects. 1

Analysis of Each Medication Option

A. Diltiazem

• Diltiazem is a non-dihydropyridine calcium channel blocker that is explicitly contraindicated in HFrEF
• The 2016 ESC guidelines clearly state: "Diltiazem or verapamil are not recommended in patients with HFrEF, as they increase the risk of HF worsening and HF hospitalization" (Class III recommendation) 1
• Multiple guidelines consistently warn against using non-dihydropyridine calcium channel blockers in HFrEF patients due to their negative inotropic effects 1
• A 2022 study showed patients with HFrEF who received diltiazem for atrial fibrillation had a significantly higher incidence of worsening heart failure symptoms compared to those who received metoprolol (33% vs 15%, P = 0.019) 2

B. Thiazide Diuretics

• Thiazides are actually recommended in HFrEF management, particularly for patients with fluid retention
• They are listed in the 2009 ACC/AHA guidelines as appropriate diuretics for HF treatment 1
• While loop diuretics are often preferred in moderate-to-severe HF, thiazides remain a viable option, especially in combination therapy for resistant fluid retention 1

C. Hydralazine

• Hydralazine is beneficial in HFrEF, not harmful
• The ESC guidelines specifically recommend hydralazine (often in combination with isosorbide dinitrate) to reduce blood pressure when hypertension persists despite standard HF therapy 1
• It's particularly valuable in patients who cannot tolerate ACE inhibitors or ARBs 3

D. Spironolactone

• Spironolactone is a mineralocorticoid receptor antagonist (MRA) that is strongly recommended in HFrEF
• The ESC guidelines give a Class I, Level A recommendation for MRAs in patients with HFrEF who remain symptomatic despite treatment with an ACE inhibitor and a beta-blocker 1
• Spironolactone has been shown to reduce mortality and hospitalization in HFrEF patients 1

Medications That Should Be Avoided in HFrEF

Beyond diltiazem, other medications to avoid in HFrEF include:

1. Non-dihydropyridine calcium channel blockers:

   • Verapamil (similar negative inotropic effects as diltiazem) 1
   • Both are Class III (harmful) in HFrEF guidelines 1

2. Most antiarrhythmic drugs:

   • Particularly class I sodium channel antagonists and class III potassium channel blockers like d-sotalol and dronedarone 1
   • Amiodarone is generally the preferred antiarrhythmic in HFrEF when needed 4

3. NSAIDs:

   • Can cause sodium and water retention
   • Blunt the effects of diuretics
   • Associated with increased morbidity and mortality in HF patients 1

4. Triple combination therapy:

   • Adding an ARB (or renin inhibitor) to the combination of an ACE inhibitor and an MRA increases risk of renal dysfunction and hyperkalemia 1

Recommended Medications for HFrEF

The cornerstone of HFrEF pharmacotherapy includes:

1. ACE inhibitors/ARBs/ARNI (Class I recommendation)
2. Beta-blockers - specifically carvedilol, metoprolol succinate, or bisoprolol (Class I)
3. Mineralocorticoid receptor antagonists like spironolactone (Class I)
4. Diuretics (including thiazides) for symptom relief in volume overload
5. SGLT2 inhibitors - newer agents showing mortality benefit
6. Hydralazine/isosorbide dinitrate - particularly valuable in specific populations

Clinical Pitfalls to Avoid

• Don't confuse dihydropyridine calcium channel blockers (like amlodipine, which may be used cautiously in HFrEF) with non-dihydropyridine agents (diltiazem, verapamil) which are contraindicated 5
• Recognize that worsening symptoms in HFrEF patients on diltiazem may be due to the medication itself rather than disease progression 2
• Remember that even medications generally contraindicated in HFrEF (like diltiazem) may be appropriate in HFpEF, so accurate classification of heart failure type is essential 1

In summary, among the listed options, diltiazem is the medication that must be avoided in patients with HFrEF due to its documented negative effects on heart failure outcomes.