What pharmacotherapy change has the potential to cause harm in a 59-year-old male with Heart Failure with Reduced Ejection Fraction (HFrEF) (Left Ventricular Ejection Fraction = 35%) and newly diagnosed atrial fibrillation, currently taking candesartan (Angiotensin Receptor Blocker) 16 mg daily and spironolactone (Mineralocorticoid Receptor Antagonist) 50 mg daily with a resting blood pressure range of mild hypertension?

Pharmacotherapy Changes That Could Cause Harm in HFrEF with Atrial Fibrillation

Initiating diltiazem 180 mg daily or nifedipine 30 mg daily would be harmful in this 59-year-old male with HFrEF (LVEF 35%) and newly diagnosed atrial fibrillation. 1

Rationale for Harmful Pharmacotherapy Options

Non-dihydropyridine Calcium Channel Blockers (Diltiazem)

• Diltiazem is specifically contraindicated in HFrEF due to its negative inotropic effects
• The 2013 ACC/AHA guidelines explicitly state that "calcium channel–blocking drugs are not recommended as routine treatment in HFrEF" with a Class III: No Benefit recommendation (Level of Evidence: A) 1
• Diltiazem can worsen heart failure by:
  • Decreasing myocardial contractility
  • Potentially worsening left ventricular function
  • Increasing risk of decompensation

Dihydropyridine Calcium Channel Blockers (Nifedipine)

• While some dihydropyridine CCBs (like amlodipine) may be tolerated in HFrEF, nifedipine is not recommended
• Nifedipine, especially in immediate-release formulations, can cause:
  • Reflex tachycardia
  • Sympathetic activation
  • Worsening of heart failure symptoms
  • Increased risk of mortality in HFrEF patients

Safe Pharmacotherapy Options

Sacubitril/Valsartan

• Transitioning from candesartan to sacubitril/valsartan 49/51 mg twice daily is appropriate
• Sacubitril/valsartan is recommended for patients with HFrEF with EF ≤40% who are currently on ACE inhibitor or ARB therapy 2
• The PARADIGM-HF trial demonstrated that sacubitril/valsartan reduced the risk of cardiovascular death or heart failure hospitalization by 20% compared to enalapril 2
• Important considerations when switching:
  • A 36-hour washout period is required when switching from an ACE inhibitor (not needed when switching from an ARB like candesartan)
  • Blood pressure, renal function, and potassium should be monitored within 1-2 weeks after initiation

Beta-Blockers

• Initiating carvedilol 3.125 mg twice daily is appropriate and beneficial
• Beta-blockers are a cornerstone of HFrEF management with a Class I recommendation (Level of Evidence: A) 1
• Carvedilol specifically has been shown to reduce mortality in HFrEF patients
• Low-dose initiation (3.125 mg twice daily) with gradual uptitration is the recommended approach
• Beta-blockers are also beneficial for rate control in atrial fibrillation

Guideline-Directed Medical Therapy for HFrEF with AF

The 2017 ACC/AHA/HFSA guidelines recommend the following core medications for HFrEF 1:

1. ACE inhibitor, ARB, or ARNI (sacubitril/valsartan)
2. Evidence-based beta-blocker (carvedilol, metoprolol succinate, or bisoprolol)
3. Mineralocorticoid receptor antagonist (spironolactone or eplerenone)
4. Diuretics as needed for volume control

For patients with concomitant atrial fibrillation:

• Beta-blockers are preferred for rate control
• Non-dihydropyridine calcium channel blockers (diltiazem, verapamil) should be avoided due to negative inotropic effects
• Anticoagulation should be considered based on stroke risk assessment

Key Clinical Pearls

• Always avoid non-dihydropyridine calcium channel blockers (diltiazem, verapamil) in HFrEF patients
• Use caution with dihydropyridine CCBs in HFrEF; amlodipine may be tolerated but nifedipine should be avoided
• When initiating beta-blockers in HFrEF, start at low doses and uptitrate gradually
• Sacubitril/valsartan is an appropriate replacement for ACE inhibitors or ARBs in eligible HFrEF patients
• Spironolactone should be continued as it provides mortality benefit in HFrEF patients