Clinical question: What is the time to benefit for patients with heart failure (HF) and prescribed a sodium-glucose cotransporter-2 (SGLT-2) inhibitor?
Background: SGLT-2 inhibitors are an effective medication for patients with heart failure and preserved (HFpEF) or reduced ejection fraction (HRrEF).
Study design: Comparative effectiveness study
Setting: The authors conducted a systematic review of the literature up to the date of September 5, 2022. 636 articles were identified, and 449 papers were excluded due to meeting the exclusion criteria of a meta-analysis, review, nonhuman research study, correspondence, or editorial. Ultimately, the researchers settled five trials for the analysis: EMPEROR Preserved; EMPEROROR-Reduced; DAPA-HF; SOLOIST-WHF; and DELIVER. The data was reconstructed, and the authors analyzed the individualized time-to-event data set.
The study population consisted of 21,947 patients in the five trials with median age greater than 65 years, 35.7% female. The primary outcome was a composite of cardiovascular (CV) death and worsening heart failure, while the secondary outcomes were cardiovascular deaths, all-cause mortality, and hospitalization for heart failure.
Synopsis: The Kaplan-Meier curve of the pool data from the five studies demonstrated a consistently decreased incidence of CV death or worsening of heart failure for those patients receiving an SGLT-2 inhibitor (HR, 0.77; 95% CI, 0.73 to 0.82, P <0.01). Moreover, there was a reduction over time with SGTL-2 inhibitors that reached statistical significance by day 26 and sustained significance at day 118. There were several limitations to this comparative effectiveness research study that relied on an administrative database. To begin with, even though the five studies selected had similarities, differences and heterogeneity still exist. The SGLT-2 inhibitors were different medications pitted against a placebo.
Bottom line: SGLT-2 inhibitors may take effect in patients with HFpEF and HFrEF as early as 26 days and have a sustained benefit at 3.93 months. More studies should be conducted to further define the association.
Citation: Vaduganathan M, et al. SGLT2 inhibitors in patients with heart failure: a comprehensive meta-analysis of five randomised controlled trials. Lancet. 2022;400(10354):756-67.
Dr. Huang
Dr. Huang is the specialty medical director at Advocate Health, and an associate professor of internal medicine, at Wake Forest School of Medicine, both in Winston-Salem, N.C. Disclosure: Dr. Huang is on the scientific advisory board for Medicus Tek and is a hospital medicine editor for Dynamed/EBSCO.