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Comparative Outcomes of Empagliflozin to Dapagliflozin in HF Patients
Quick Takes
- Empagliflozin is associated with reduced all-cause mortality and hospitalization when compared to dapagliflozin in patients with HF.
- Results were driven by a reduction in hospitalization at 1 year with no significant differences in mortality between empagliflozin and dapagliflozin.
Study Questions:
Are there differences between empagliflozin and dapagliflozin for the composite outcome of all-cause mortality and hospitalization in patients with heart failure (HF)?
Methods:
Patients with HF and no prior exposure to a sodium-glucose cotransporter-2 (SGLT2) inhibitor newly started on empagliflozin or dapagliflozin were identified from the TriNetX Research Collaborative Network database of 81 health care organizations. Empagliflozin-treated patients were designated as the intervention group and those receiving dapagliflozin were the comparator group. An intent-to-treat study design was used, analyzing patients according to the initial SGLT2 inhibitor prescribed.
The primary outcome was the composite of all-cause mortality or hospitalization from day zero (first day of SGLT2 inhibitor treatment) through 1-year follow-up. Cause-specific mortality or hospitalizations were not able to be determined due to database limitations. Secondary outcomes included all-cause mortality, hospitalization, and last measured glycated hemoglobin (HbA1c). Adverse effects evaluated were urinary tract infections and diabetic ketoacidosis. Covariables including demographics, comorbidities, glomerular filtration rate, HbA1c, natriuretic peptides, left ventricular ejection fraction (LVEF), and hospitalizations were extracted.
Propensity scores were generated for empagliflozin vs. dapagliflozin initiation using logistic regression and included covariables in the model. Cohort identification and statistical analyses were conducted using the TriNetX Platform Query Builder and Analytics Functions, respectively.
Results:
There were 744,914 patients with HF and naïve to SGLT2 inhibitor therapy available in the database, of which 15,976 (56.9%) received empagliflozin and 12,099 (43.1%) received dapagliflozin. After matching for demographics, diagnoses, and medication use, there were 11,077 in each group. Patients receiving empagliflozin were 57.9% male, 19.6% Black, and 59.9% White. Those treated with dapagliflozin were 61.5% male, 20.2% Black, and 58.9% White.
Empagliflozin-treated patients were less likely to experience the primary composite outcome of all-cause mortality or hospitalization compared with those treated with dapagliflozin, 3,545 [32.2%] vs. 3,828 [34.8%] events (hazard ratio [HR], 0.90; 95% confidence interval [CI], 0.86-0.94) within 1 year of SGLT2 inhibitor initiation. Patients receiving empagliflozin were also less likely to be hospitalized compared to those receiving dapagliflozin (HR, 0.90; 95% CI, 0.86-0.94). All-cause mortality did not differ between groups (HR, 0.91; 95% CI, 0.82-1.00). Mean HbA1c and adverse event rates did not differ between groups.
Conclusions:
In this study, patients with HF and no prior SGLT2 inhibitor use treated with empagliflozin were less likely to experience all-cause mortality or hospitalization compared with patients treated with dapagliflozin during the first year of use. Composite endpoint differences were driven by a reduction in hospitalization for empagliflozin-treated patients, as there were no significant differences in mortality between groups.
Perspective:
Both empagliflozin and dapagliflozin have been proven to reduce cardiovascular death and HF hospitalizations in patients with HF in respective randomized controlled trials. Empagliflozin has been shown to result in improved LVEF and functional status compared to dapagliflozin in a single-center retrospective study but comparisons of clinically important patient-centered outcomes for HF for the two SGLT2 inhibitors are lacking. Results of the current trial, together with the prior study, suggest differences may exist in the degree of cardiac remodeling between agents within the SGLT2 class. However, a recent meta-analysis showed similar improvements in cardiovascular outcomes between empagliflozin and dapagliflozin when compared to placebo. Disparity in results may be attributed to differences in medication adherence and/or difference in comorbidity burden and treatments. Future studies should aim to directly compare outcomes of empagliflozin and dapagliflozin in a comparative effectiveness randomized controlled trial.
Clinical Topics: Heart Failure and Cardiomyopathies, Acute Heart Failure, Cardiovascular Care Team
Keywords: Heart Failure, Novel Agents, Sodium-Glucose Transporter 2 Inhibitors
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