Meta-Analysis Details Effects of SGLT2 Inhibitors in HFpEF

Vass Vassiliou, MBBS, PhD

Results of a systematic review and meta-analysis of phase 3 data on SGLT2 inhibitors and heart failure with preserved ejection fraction (HFpEF) is providing clinicians with an overview of the effects of the class in this patient population.

With data from 5 major trials and nearly 10,000 patients, results detail the effects of agents within the class on composite and individual end points, including all-cause mortality and cardiovascular death, among patients with an ejection fraction of 40% or greater.

“For many years there was not a single medicine that could improve the outcome in patients with the second type of heart failure – those patients with preserved ejection fraction. This type of heart failure had puzzled doctors, as every medicine tested showed no benefit,” said lead investigator Vass Vassiliou, MBBS, PhD, professor at the University of East Anglia and an honorary consultant cardiologist at the Norfolk and Norwich University Hospital, in a statement. “One class of heart medication, called SGLT2 inhibitors, was initially used for patients with diabetes. However, it was noticed that it also helped patients who had heart failure. Previous studies had shown that this medication would be beneficial in heart failure with reduced ejection fraction. But we found that it can also help heart failure patients with preserved ejection fraction.”

Spurred by the publication of EMPEROR-PRESERVED results, Vassiliou and a team of colleagues sought to evaluate the effects of SGLT2 inhibitors in HFpEF from clinical trials. After performing a search of the PubMed, Embase, Cochrane, and Web of Science databases from inception through August 27, 2021, investigators identified 5 studies for inclusion in their review and meta-analysis.

Search terms used included ‘SGLT2’, ‘Sodium-glucose cotransporter-2 inhibitors’, ‘canagliflozin’, ‘dapagliflozin’, ‘empagliflozin’, ‘ertugliflozin’, and ‘heart failure’. For inclusion, studies needed to have at least 6 months of follow-up. The initial search returned 9493 particles of which 167 underwent full-text screening.

The 5 studies included were EMPEROR-PRESERVED, VERTIS-CV, DECLARE-TIMI 58, SOLOIST-WHF, and SCORED. From these studies, investigators obtained data related to 9726 patients, including 5046 receiving an SGLT2 inhibitor and 4680 receiving placebo therapy. Outcomes of interest for the current study were effects of SGLT2 inhibitor use on cardiovascular death or hospitalizations for heart failure, hospitalizations for heart failure, cardiovascular death, and all-cause mortality. Investigators noted a random-effects model with inverse-variance weights was used to combine the effect measures from all studies on a logarithmic scale.

Results suggested SGLT2 inhibitor use was associated with a significant reduction in cardio vascular death or hospitalization for heart failure (HR, 0.78 [95% CI, 0.69-0.87]; I²=0%) and in hospitalization for heart failure (HR, 0.71 [95% CI, 0.61-0.84]; I²=0%), but no significant differences were observed in regard to cardiovascular death (HR, 1.01 [95% CI, 0.80- 1.28]; I²=23%) and all-cause mortality (HR, 1.01 [95% CI, 0.89-1.14]; I²=0%) compared to placebo therapy. In a prespecified subanalysis of patients with an ejection fraction greater than 50%, which included 5928 patients, SGLT2 inhibitor use was associated with a significant reduction in cardiovascular death or hospitalization for heart failure (HR, 0.77 [95% CI, 0.66-0.91]; I²=22%).

“We found that patients taking SGLT2 inhibitors were 22% less likely to die from heart-related causes or be hospitalized for heart failure exacerbation than those taking placebo,” Vassiliou added. “This is very important because this is the first medication that can provide a benefit to this previously untreatable group of patients—in terms of heart-related deaths or hospitalization.”

This study, “Sodium glucose co-transporter 2 inhibitors in heart failure with preserved ejection fraction: a systematic review and meta-analysis,” was published in the European Journal of Preventive Cardiology.