Yes, this patient is a candidate for Jardiance (empagliflozin) in HFpEF
Based on the most recent 2025 Canadian Cardiovascular Society guidelines and the EMPEROR-Preserved trial, empagliflozin is strongly recommended for HFpEF patients and should be initiated in this case. 1 The presence of severe coronary artery disease, combined pulmonary fibrosis-emphysema (CPFE), and concurrent Breztri use do not constitute contraindications.
Evidence Supporting Use in HFpEF
The EMPEROR-Preserved trial demonstrated that empagliflozin 10 mg daily reduced cardiovascular death or heart failure hospitalization by 21% (HR 0.79,95% CI 0.69-0.90) in patients with LVEF >40%. 2 This benefit was driven primarily by a 29% reduction in heart failure hospitalizations. 3 The 2025 CCS/CHFS guidelines now list SGLT2 inhibitors (empagliflozin 10-25 mg daily or dapagliflozin 10 mg daily) as first-line therapy for HFnrEF (LVEF >40%). 1
Addressing Specific Comorbidities
Severe Coronary Artery Disease: This is not a contraindication—in fact, it strengthens the indication. The 2020 ACC Expert Consensus specifically recommends SGLT2 inhibitors for patients with type 2 diabetes and established cardiovascular disease to reduce heart failure hospitalization and death. 4 Even without diabetes, coronary disease increases HFpEF risk and empagliflozin provides cardiovascular protection. 5
Combined Pulmonary Fibrosis-Emphysema: While not specifically studied in CPFE, empagliflozin's safety profile in HFpEF trials showed no respiratory contraindications. 6 The drug works through renal mechanisms (SGLT2 inhibition) and does not adversely affect pulmonary function. There are no known interactions between empagliflozin and the pathophysiology of interstitial lung disease or emphysema.
Breztri (ICS/LABA/LAMA) Concurrent Use: No drug-drug interactions exist between empagliflozin and inhaled corticosteroids, long-acting beta-agonists, or long-acting muscarinic antagonists. 6 The FDA label for Jardiance does not list any respiratory medications as contraindications or requiring dose adjustments. 6
Key Safety Considerations
Renal Function: Check eGFR before initiation. Empagliflozin can be used with eGFR ≥20 mL/min/1.73 m² based on EMPEROR-Preserved inclusion criteria. 7 The drug causes a transient eGFR decrease (typically <9 mL/min/1.73 m²) within 4 weeks that stabilizes and reverses after discontinuation. 6
Volume Status: Assess for volume depletion before starting, particularly important given potential diuretic effects. 7 If the patient is on loop diuretics for heart failure, monitor closely but do not withhold empagliflozin—the EMPEROR trials showed benefit on top of standard diuretic therapy. 2
Diabetes Status: Empagliflozin benefits are independent of diabetes status. 8 If the patient has diabetes, reduce insulin or sulfonylurea doses to prevent hypoglycemia. 4 If no diabetes, hypoglycemia risk is negligible.
Practical Implementation
Starting Dose: Initiate empagliflozin 10 mg once daily in the morning, with or without food. 6
Monitoring Schedule:
- Renal function and potassium at 1 week, then at 4 weeks
- Volume status assessment at each visit
- Genital mycotic infection surveillance (most common adverse effect: 3.7-4.1% incidence) 6
Sick Day Management: Educate the patient to hold empagliflozin during acute dehydrating illnesses (vomiting, diarrhea, fever) to prevent volume depletion and acute kidney injury. 7 This is critical given the CPFE diagnosis, as respiratory infections may be more frequent.
Contraindications to Verify: Confirm the patient is not on dialysis, does not have type 1 diabetes, and has no history of serious hypersensitivity to empagliflozin. 6 These are the only absolute contraindications.
Expected Benefits
Based on EMPEROR-Preserved data, treating 1000 HFpEF patients prevents 74 heart failure hospitalizations and 15 cardiovascular deaths over the trial period. 9 The patient should experience improved quality of life (measured by KCCQ scores) and reduced dyspnea within weeks to months. 1
The combination of HFpEF, severe CAD, and chronic lung disease actually increases this patient's cardiovascular risk profile, making empagliflozin's mortality and morbidity benefits even more clinically relevant. The drug should be started promptly as part of guideline-directed medical therapy for HFpEF. 10