From the Guidelines
Empagliflozin (Jardiance) 10mg daily is recommended for treating heart failure with preserved ejection fraction (HFpEF) based on the EMPEROR-Preserved trial, which demonstrated a 21% reduction in cardiovascular death or hospitalization for heart failure 1. When considering the treatment of HFpEF, it is essential to prioritize medications that have shown a significant reduction in morbidity, mortality, and improvement in quality of life.
- The EMPEROR-Preserved trial showed that empagliflozin reduced the primary composite endpoint of time to HF hospitalization or cardiovascular death by 21%, driven mostly by a significant 29% reduction in time to HF hospitalization 1.
- In contrast, dapagliflozin (Farxiga) 10mg daily is also effective, supported by the DELIVER trial showing an 18% reduction in worsening heart failure or cardiovascular death 1.
- Both medications work by increasing glucose excretion in urine, reducing blood pressure, decreasing cardiac preload and afterload, and providing anti-inflammatory effects.
- They have similar side effect profiles, including genital mycotic infections, urinary tract infections, and volume depletion.
- Neither drug requires dose adjustment for HFpEF patients with reduced renal function until eGFR falls below 20-25 ml/min.
- The choice between them often depends on formulary availability, cost considerations, and patient-specific factors rather than significant efficacy differences.
- A large recent meta-analysis of data from EMPEROR-Reduced, EMPEROR-Preserved, DAPA-HF, DELIVER, and the Effect of Sotagliflozin on Cardiovascular Events in Patients With Type 2 Diabetes Post Worsening Heart Failure (SOLOIST-WHF) trial included 21,947 individuals and demonstrated reduced risk for the composite of cardiovascular death or hospitalization for heart failure, cardiovascular death 1.
From the Research
Comparison of Dapagliflozin and Empagliflozin in HFpEF
- Both dapagliflozin and empagliflozin have been shown to be effective in the treatment of heart failure with preserved ejection fraction (HFpEF) 2, 3, 4, 5.
- A systematic review and meta-analysis found that SGLT2 inhibitors, including empagliflozin and dapagliflozin, decreased the risk of cardiovascular hospitalization in patients with HFpEF 3.
- A multicenter randomized trial found that dapagliflozin improved symptoms, physical limitations, and exercise function in patients with HFpEF 4.
- Another trial found that empagliflozin initiated in patients hospitalized for acute heart failure resulted in significant clinical benefit, regardless of ejection fraction or the presence or absence of diabetes 5.
Efficacy and Safety
- Both dapagliflozin and empagliflozin have been shown to be safe and well-tolerated in patients with HFpEF 2, 3, 4, 5.
- The mechanism of action of SGLT2 inhibitors does not depend on the state of neurohumoral activation, and they have a simple dosing regimen without the need for dose titration 6.
- SGLT2 inhibitors also have a significant nephroprotective effect, in addition to their cardioprotective properties 6.
Clinical Use
- First-line pharmacologic therapy for HFpEF consists of sodium-glucose cotransporter type 2 inhibitors, such as dapagliflozin or empagliflozin, which reduced HF hospitalization or cardiovascular death by approximately 20% compared with placebo in randomized clinical trials 2.
- Empagliflozin and dapagliflozin have recently been approved by regulatory authorities for the treatment of adults with symptomatic chronic heart failure with reduced ejection fraction and are becoming one of the basic pillars of treatment for these patients 6.