Analysis Details SGLT2 Inhibitors Benefit Across Heart Failure Subgroups

Patrick Campbell

Hear from Deepak Bhatt, MD, MPH, on a systematic review and meta-analysis of SGLT2 inhibitor trials examining the effects of the class on heart failure across multiple subgroups, including those with preserved ejection fraction.

This article was originally published on EndocrinologyNetwork.com.


A systematic review and meta-analysis of data from phase 3 trials are providing more insight into the effects of SGLT2 inhibitors on cardiovascular mortality and worsening heart failure.

The study, which was presented at the American College of Cardiology’s 70th Annual Scientific Session (ACC.21), used data from 9 trials and more than 19,000 patients and determined use of any SGLT2 inhibitor was associated with a 15% reduction in mortality, a 13% reduction in cardiovascular mortality, and a more than 30% reduction in risk of hospitalization for heart failure.

With major trials outlining the benefits of specific SGLT2 inhibitors in patients heart failure, Deepak Bhatt, MD, MPH, and colleagues from Brigham and Women’s and Harvard Medical School designed the current study to compare SGLT2 inhibitors against placebo on mortality, hospitalizations, and in subgroup analyses based on sex, age, renal function, heart failure class, and ejection fraction.

Studies included in the systematic review and meta-analysis were CANVAS, DAPA-HF, DECLARE-TIMI, EMPA-REG, EMPEROR, SOLOIST-WHF, SCORED, and VERTIS-CV. Of note, VERTIS-CV data were stratified based on whether a patient’s ejection fraction was above or below 45%. The specific SGLT2 inhibitors examined in these studies were canagliflozin, empagliflozin, dapagliflozin, and ertugliflozin. Sotagliflozin, a dual SGLT1/2 inhibitor, was also included.

From the 9 studies and 19,091 patients included in the study, 10,018 (52.5%) received an SGLT2 inhibitor and the mean follow-up among trials included in the study ranged from 3 months to 4.2 years. Initial analysis indicated SGLT2 inhibitor use was associated with significantly lower rates of all-cause mortality (HR, 0.85; 95% CI, 0.78-0.94), cardiovascular mortality (HR, 0.87; 95% CI, 0.78-0.96), and heart failure hospitalization (HR, 0.69; 95% CI, 0.62-0.76).

Further analysis, using a composite endpoint of cardiovascular mortality, heart failure hospitalization, or urgent visits for heart failure, revealed SGLT2 inhibitors were associated with significantly lower risk of this endpoint, regardless of sex, age, baseline eGFR, NYHA class, and ejection fraction (HR, 0.77; 95% CI, 0.62-0.97).

For more on the results of this study, check out our interview Bhatt.

This study, “SGLT2 Inhibitors Decrease Cardiovascular Mortality or Heart Failure Hospitalizations in Heart Failure Subgroups: A Systematic Review and Meta-Analysis,” was presented at ACC.21.