Should dapagliflozin (SGLT2 inhibitor) be continued or discontinued in patients with heart failure who develop an infection?

Dapagliflozin Should Be Continued During Infection in Heart Failure Patients

Continue dapagliflozin during infection in patients with heart failure unless there is hemodynamic instability, severe volume depletion, or acute kidney injury requiring dialysis. The cardiovascular mortality and heart failure hospitalization benefits of SGLT2 inhibitors outweigh theoretical infection-related concerns, and guideline evidence supports continuation during acute illness.

Rationale for Continuation

Evidence from COVID-19 and Acute Illness

• The 2021 ACC Expert Consensus explicitly states that renin-angiotensin-aldosterone system inhibitors should be continued during COVID-19 infection as long as hemodynamically tolerated, establishing the precedent that guideline-directed medical therapies for heart failure should not be routinely discontinued during infection 1
• This same principle applies to SGLT2 inhibitors like dapagliflozin, which are now Class I guideline-directed medical therapy for heart failure with the same level of evidence as ACE inhibitors 1

Cardiovascular Benefits That Should Not Be Interrupted

• Dapagliflozin reduces cardiovascular death by 18% and heart failure hospitalizations by 30% in patients with HFrEF, with benefits occurring within weeks of initiation 1, 2
• The medication reduces the composite of cardiovascular death or worsening heart failure by approximately 25% across the ejection fraction spectrum 1
• Discontinuing dapagliflozin during infection removes this protective effect at a time when patients may be at higher risk for cardiovascular decompensation 3

Specific Clinical Scenarios Requiring Temporary Discontinuation

Volume Depletion States

• Temporarily hold dapagliflozin if the patient develops severe diarrhea causing dehydration, similar to the approach with mineralocorticoid receptor antagonists 1
• Monitor for hypotension (occurs in approximately 5.7% of patients), especially in volume-depleted states 2
• Adjust loop diuretics as needed rather than discontinuing dapagliflozin 1

Acute Kidney Injury

• Continue dapagliflozin even if eGFR deteriorates to <25 mL/min/1.73 m², as patients with deteriorating renal function appear to benefit from continuation with no excess safety outcomes 4
• The benefit-to-risk ratio favors continuation in patients experiencing deterioration of kidney function, with a 47% relative risk reduction in the primary outcome even when eGFR falls below 25 4
• Only discontinue if acute kidney injury requires dialysis or there is severe acute tubular necrosis 4

Hemodynamic Instability

• Hold dapagliflozin if the patient requires IV vasopressors or inotropes for septic shock or cardiogenic shock 2
• Once hemodynamically stable (no increase in IV diuretics for 6 hours, no IV vasodilators or inotropes for 24 hours), dapagliflozin can be safely restarted 2

Infection-Specific Considerations

Genital and Urinary Tract Infections

• Genital mycotic infections occur in 1.5-1.7% and urinary tract infections in 2.3-2.7% of patients on dapagliflozin 2
• These infections are manageable with standard antimicrobial therapy and do not require discontinuation of dapagliflozin 1, 2
• The 2022 AHA/ACC/HFSA guidelines specifically note that SGLT2 inhibitors increase risk for genital infections but were otherwise well tolerated in trials 1

Soft Tissue Infections

• The guidelines caution about soft tissue infections but do not recommend routine discontinuation 1
• Treat the infection with appropriate antibiotics while continuing dapagliflozin unless there is necrotizing fasciitis or Fournier's gangrene (extremely rare) 1

Systemic Infections (Pneumonia, Sepsis, etc.)

• No specific evidence suggests discontinuation during pneumonia or other systemic infections 1
• The key is maintaining adequate volume status and hemodynamic stability, not the presence of infection itself 1, 2

Ketoacidosis Risk Assessment

Risk in Non-Diabetic Patients

• Euglycemic ketoacidosis risk is significantly lower in non-diabetic heart failure patients compared to diabetic patients 2
• The 2022 guidelines note caution for euglycemic ketoacidosis but this was rare in the DAPA-HF trial where 55% of patients did not have diabetes 1

Risk During Infection

• Infection can be a precipitating factor for ketoacidosis, but this is primarily a concern in diabetic patients with additional risk factors 1
• Monitor for symptoms of ketoacidosis (nausea, vomiting, abdominal pain, altered mental status) but do not routinely discontinue dapagliflozin during infection 1

Algorithm for Decision-Making During Infection

Step 1: Assess Hemodynamic Status

• If requiring IV vasopressors or inotropes → Hold dapagliflozin temporarily 2
• If hemodynamically stable → Continue dapagliflozin 1, 2

Step 2: Assess Volume Status

• If severe volume depletion (severe diarrhea, inability to maintain oral intake) → Hold temporarily 1
• If adequate volume status or mild dehydration → Continue with IV fluids as needed 1

Step 3: Assess Renal Function

• If eGFR deteriorates but remains >20 mL/min/1.73 m² → Continue dapagliflozin 4
• If eGFR <25 mL/min/1.73 m² but stable → Continue dapagliflozin (benefits persist) 4
• If acute kidney injury requiring dialysis → Hold temporarily 4

Step 4: Monitor for Ketoacidosis (Primarily in Diabetic Patients)

• Check for symptoms: nausea, vomiting, abdominal pain, altered mental status 1
• If ketoacidosis suspected → Hold dapagliflozin and check ketones 1
• If no ketoacidosis → Continue dapagliflozin 1

Common Pitfalls to Avoid

• Do not reflexively discontinue dapagliflozin simply because a patient has an infection - this removes critical cardiovascular protection 1
• Do not confuse the approach to metformin (which should be held during acute illness) with dapagliflozin - these are different drug classes with different risk profiles 1
• Do not hold dapagliflozin for mild transient decreases in eGFR - this is expected and does not indicate kidney injury 2, 4
• Do not discontinue for manageable genital or urinary tract infections - treat the infection while continuing the medication 1, 2

Resumption After Temporary Discontinuation

• Restart dapagliflozin as soon as the patient is hemodynamically stable and volume replete 2
• No dose titration is required - simply resume the standard 10 mg daily dose 2, 5
• Benefits occur within weeks of reinitiation 2