What other medications are avoided in patients with heart failure with preserved ejection fraction (HFpEF) and liver failure?

Medications to Avoid in Patients with HFpEF and Liver Failure

In patients with heart failure with preserved ejection fraction (HFpEF) and liver failure, non-steroidal anti-inflammatory drugs (NSAIDs), non-dihydropyridine calcium channel blockers (diltiazem and verapamil), and thiazolidinediones (TZDs) should be strictly avoided due to their potential to worsen both cardiac and hepatic function.

Key Medications to Avoid

1. NSAIDs

• NSAIDs cause sodium and water retention, blunt the effects of diuretics, and are associated with increased morbidity and mortality in heart failure patients 1
• In patients with severe hepatic impairment, NSAIDs increase the risk of complications including bleeding, gastrointestinal irritation, and renal failure 2
• The risk of hepatorenal syndrome is significantly increased when NSAIDs are used in patients with liver disease 3

2. Calcium Channel Blockers

• Non-dihydropyridine calcium channel blockers (diltiazem and verapamil) are contraindicated in all forms of heart failure due to their negative inotropic effects 1
• The European Society of Cardiology guidelines specifically state that diltiazem and verapamil are not recommended in heart failure patients as they increase the risk of HF worsening and hospitalization 1
• These drugs are classified as Class III (harmful) in heart failure guidelines 1

3. Thiazolidinediones (TZDs)

• TZDs are contraindicated in all patients with established heart failure 4
• They cause fluid retention and volume expansion through increased renal sodium reabsorption 4
• The American Heart Association and Heart Failure Society of America explicitly state that TZDs are contraindicated in HF patients, regardless of ejection fraction 4

4. Other Medications Requiring Caution

Antiarrhythmic Drugs

• Most antiarrhythmic drugs, particularly class I sodium channel antagonists and class III potassium channel blockers (d-sotalol and dronedarone), should be avoided 1

Opioid Analgesics

• Certain opioids should be avoided or used with extreme caution:
  • Pethidine (meperidine) has toxic metabolites that can accumulate in liver disease 2
  • Codeine and tramadol rely on hepatic biotransformation to active metabolites, which may be impaired 2
  • All opioids can precipitate or aggravate hepatic encephalopathy in severe liver disease 2

ACE Inhibitors/ARBs

• While these are cornerstone therapies for heart failure, they require careful monitoring in liver failure
• ACE inhibitors may counteract adaptive physiological processes in advanced liver disease, creating risk of excessive hypotension 3
• Dose reduction and careful monitoring are essential when these medications cannot be avoided

Medication Management Approach

1. Assess liver function severity:

   • Evaluate liver function tests, particularly bilirubin, alkaline phosphatase, albumin, and coagulation parameters
   • Elevated bilirubin and alkaline phosphatase are associated with poor outcomes in HFpEF patients 5, 6

2. Prioritize safer alternatives:

   • For pain management: Consider acetaminophen at reduced doses (maximum 2g daily) for short-term use in non-alcoholic liver disease 2
   • For hypertension control: Amlodipine (dihydropyridine CCB) is safer than non-dihydropyridine CCBs 4
   • For diabetes management: Consider SGLT2 inhibitors if renal function permits, as they may decrease risk of HF hospitalization 4

3. Medication dosing adjustments:

   • Lower doses and/or longer administration intervals for medications that undergo significant hepatic metabolism
   • Monitor drug levels when available
   • Consider renal function, which is often impaired in advanced liver disease

By carefully avoiding these contraindicated medications and appropriately adjusting necessary therapies, clinicians can optimize management of patients with the challenging combination of HFpEF and liver failure.