Can Sodium-Glucose Cotransporter 2 (SGLT2) inhibitors be used in patients with heart failure and concomitant liver cirrhosis?

SGLT2 Inhibitors in Heart Failure Patients with Concomitant Liver Cirrhosis

SGLT2 inhibitors can be used in heart failure patients with compensated cirrhosis (Child-Pugh A and B), but should be avoided in decompensated cirrhosis due to risks of hemodynamic instability and acute kidney injury. 1

Patient Selection Based on Cirrhosis Severity

Compensated Cirrhosis (Child-Pugh A and B)

• SGLT2 inhibitors are appropriate for patients with Child-Pugh class A and B cirrhosis who have heart failure, with the strongest evidence supporting use in Child-Pugh A cirrhosis. 1
• The American Diabetes Association recommends SGLT2 inhibitors specifically in Child-Pugh class A and B cirrhosis, distinguishing them from GLP-1 receptor agonists which are only recommended in Child-Pugh A. 1
• Recent real-world evidence from over 10,000 propensity-matched cirrhotic patients showed SGLT2 inhibitor use was associated with a 32% reduction in serious liver events (HR 0.68,95% CI 0.66-0.71). 2

Decompensated Cirrhosis

• SGLT2 inhibitors should be avoided in decompensated cirrhosis due to risks of hemodynamic instability and acute kidney injury. 1
• The European Association for the Study of the Liver specifically recommends against use in decompensated cirrhosis. 1

Heart Failure Indications Remain Valid

HFrEF (LVEF ≤40%)

• SGLT2 inhibitors are Class 1 recommendations for HFrEF patients to reduce cardiovascular death and heart failure hospitalization, irrespective of diabetes status. 3
• The 2024 ACC/AHA guidelines designate SGLT2 inhibitor prescription as a quality measure for all HFrEF patients unless contraindicated. 3
• Medical exceptions include eGFR <20 mL/min/1.73 m², type 1 diabetes, and documented intolerance. 3

HFmrEF and HFpEF (LVEF >40%)

• SGLT2 inhibitors are Class 2a recommendations for HFmrEF and HFpEF to decrease heart failure hospitalizations and cardiovascular mortality. 3
• These recommendations apply irrespective of diabetes status. 3

Specific Benefits in Cirrhotic Patients with Heart Failure

Liver-Related Outcomes

• SGLT2 inhibitors reduced hepatorenal syndrome by 53% (HR 0.47,95% CI 0.40-0.56) in cirrhotic patients. 2
• Spontaneous bacterial peritonitis was reduced by 45% (HR 0.55,95% CI 0.46-0.65). 2
• Paracentesis requirements decreased by 46% (HR 0.54,95% CI 0.50-0.60). 2
• Variceal bleeding was reduced by 21% (HR 0.79,95% CI 0.73-0.84). 2

Cardiovascular and Renal Safety

• SGLT2 inhibitors are not associated with clinically relevant risks of hypotension or volume depletion in heart failure patients. 4
• Acute kidney injury risk was actually reduced by 31% (RR 0.69,95% CI 0.51-0.93) in heart failure populations. 4
• In cirrhotic patients specifically, acute kidney injury was reduced by 20% (HR 0.797,95% CI 0.779-0.816). 5

Mechanisms Supporting Use in Cirrhosis with Heart Failure

• SGLT2 inhibitors cause natriuresis and osmotic diuresis through mechanisms distinct from conventional diuretics, potentially beneficial for refractory ascites. 6
• They inhibit the renin-angiotensin-aldosterone system and ameliorate sympathetic nervous system activation—pathways shared between decompensated cirrhosis and congestive heart failure. 7, 6
• Hepatoprotective effects through ketone bodies and adiponectin may provide additional liver benefits. 6

Practical Implementation Algorithm

Step 1: Assess Cirrhosis Severity

• Child-Pugh A or B with compensated cirrhosis → Proceed to Step 2
• Decompensated cirrhosis → Do not initiate SGLT2 inhibitor 1

Step 2: Verify Heart Failure Indication

• LVEF ≤40% → Strong Class 1 indication 3
• LVEF >40% with NYHA Class II-IV symptoms → Class 2a indication 3
• NYHA Class I with LVEF >40% → Not indicated 3

Step 3: Check for Contraindications

• eGFR <20 mL/min/1.73 m² → Contraindicated 3
• Type 1 diabetes → Contraindicated 3
• Active decompensation (new ascites, encephalopathy, variceal bleeding) → Defer initiation 1

Step 4: Monitor After Initiation

• Frequent monitoring of organ function including liver, kidney, and hemodynamic parameters is recommended, as both cirrhosis and heart failure are dynamic conditions. 1
• All-cause hospitalizations were reduced by 33% (HR 0.67,95% CI 0.63-0.71) in cirrhotic patients on SGLT2 inhibitors, suggesting overall clinical benefit. 2

Critical Caveats

• The mortality benefit in cirrhotic patients on SGLT2 inhibitors was substantial (HR 0.600,95% CI 0.580-0.621), suggesting benefits extend beyond heart failure management alone. 5
• No increased hypoglycemia risk was observed in cirrhotic populations (HR 0.963,95% CI 0.914-1.014). 5
• The combination with furosemide and spironolactone appears safe and potentially synergistic in managing both ascites and heart failure. 2