Real-World Data Find Few Differences in Cardiovascular Outcomes between SGLT2 Inhibitors and GLP1 Agonists
Presenter: Juan J. Badimon, PhD
In patients with stable heart failure with reduced ejection fraction (HFrEF) without a diagnosis of diabetes, the sodium-glucose cotransporter 2 (SGLT2) inhibitor improved indices of cardiac remodeling compared with placebo.
Results from the EMPA-TROPISM trial—Are the "Cardiac Benefits" of Empagliflozin Independent of Its Hypoglycemic Activity? (NCT03485222)—demonstrated benefits of empagliflozin on cardiac volume, mass, function, and architecture and a significant improvement in cardiopulmonary capacity in this patient population, reported Juan J. Badimon, PhD, director of the Atherothrombosis Research Unit at the Icahn School of Medicine at Mount Sinai, New York City.
“Our data suggest that specific inhibition of the SGLT receptor could be a new therapeutic strategy for the treatment of HFrEF independently of the glycemic status,” he said.
In previous trials of patients with type 2 diabetes, SGLT2 inhibitors improved cardiovascular and renal outcomes, including heart failure hospitalizations, evidence of the presence of a class effect. Whether these improvements would extend to patients with HFrEF without diabetes formed the rationale of the single-center EMPA-TROPISM trial. A total of 84 patients with New York Heart Association class II to III heart failure and a left ventricular (LV) ejection fraction less than 50% and who had stable symptoms and were on therapy for heart failure within the previous 3 months were randomized in double-blind fashion to 6 months of empagliflozin 10 mg/day or placebo.
Mean age of participants was 61.9, 36% were women, and 50% were of Hispanic/Latino ethnicity; 76% of patients were on a statin, 85% on an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, 89% on a beta blocker, 54% on a loop diuretic, 66% on an antiplatelet agent, and 41% on an angiotensin receptor neprilysin inhibitor. The mean LVEF was 36.5%.
Two patients in each arm were lost to follow-up, leaving 40 in each arm for analysis.
The change in left ventricular end-systolic volume from baseline to 6 months, a coprimary end point, was -26.6 mL in the empagliflozin arm compared with -0.54 mL in the placebo arm (P < .001). The change in LV end-diastolic volume, the other co-primary end point, was 25.1 mL in those randomized to empagliflozin vs -1.5 in the patients randomized to placebo (P < .001).
Secondary outcomes also favored empagliflozin. From baseline to 6 months, the change in LV ejection fraction was -6.0% in the empagliflozin group vs -0.1% in the placebo group (P < .001), the change in LV mass was -17.8 g/m2 in the empagliflozin group vs 4.1 g/m2 in the placebo group (P < .001), the change in peak oxygen uptake was 1.1 mL/kg/min in the empagliflozin arm vs -0.5 mL/kg/min in the placebo arm (P = .017), and the change in the 6-minute walk test was 82 m in the empagliflozin arm vs -35 m in the placebo arm (P < .001).
“Therefore, with all of these changes, we should not be surprised when the patient-reported quality of life was significantly improved in the empagliflozin group compared with the placebo group,” said Dr. Badimon. The score on the Kansas City Cardiomyopathy Questionnaire improved from baseline by 37% in the empagliflozin arm compared with 5% in the placebo arm.
Dr. Badimon has disclosed no relevant relationships.