CVD
Corey Diamond, PharmD
SGLT-2 inhibitors have demonstrated significant efficacy in the management of heart failure. The American College of Cardiology, American Heart Association, and Heart Failure Society of America recommend SGLT-2 inhibitors for patients with heart failure with reduced ejection fraction (HFrEF) due to their substantial benefits in reducing cardiovascular death and heart failure hospitalizations.
Strong evidence from clinical trials demonstrates the efficacy of SGLT-2 inhibitors. However, their impact on broader heart failure populations encountered in routine clinical settings remains largely uncertain.
A recent study published in the November 16, 2024, issue of The BMJ by Svanström and colleagues sought to conduct an observational analysis using a real-world experimental design. The analysis revealed that the use of SGLT-2 inhibitors was linked to a 25% reduction in the risk of death from any cause in patients with HFrEF.
Study design and overview
Svanström and colleagues conducted a noninterventional, observational database analysis in Denmark, leveraging data from the Danish Heart Failure Registry and other national registries. It aimed to examine the association between SGLT-2 inhibitor use and the risk of all-cause mortality in patients with HFrEF. The study period spanned from July 2020 to June 2023.
Patients aged 45 years or older with a left ventricular ejection fraction of 40% or less were included. Participants were divided into two groups: those initiating treatment with SGLT-2 inhibitors (i.e., dapagliflozin or empagliflozin) and those continuing treatment with other standard heart failure drugs without SGLT-2 inhibitors.
A “modified prevalent new user design” was employed to balance baseline characteristics between the groups. Propensity score weighting was used to adjust for potential
confounders, including demographics, comorbidities, and treatment history.
The study’s primary outcome was all-cause mortality, while secondary outcomes included cardiovascular mortality and hospital admissions for heart failure. Subgroup analyses considered factors such as age, sex, diabetes status, and renal function. To minimize bias, individuals were excluded if they had prior SGLT-2 inhibitor use, heart transplant, end-stage renal disease, or other conditions suggesting severe frailty.
To further validate findings, sensitivity analyses were conducted, including an intention-to-treat approach and adjustments for key biomarkers such as NT-proBNP. This comprehensive methodology allowed for a robust evaluation of the real-world effectiveness of SGLT-2 inhibitors in managing HFrEF.
Results
The study found that among patients with HFrEF, the use of SGLT-2 inhibitors significantly reduced the risk of death from all causes compared with standard heart failure therapies without these drugs.
Specifically, SGLT-2 inhibitor use was linked to a 25% lower risk of all-cause mortality, with an incidence rate of 5.8 deaths per 100 person-years in the SGLT-2 group versus 8.5 deaths per 100 person-years in the comparator group.
For cardiovascular outcomes, SGLT-2 inhibitors demonstrated a 23% reduction in cardiovascular mortality. However, there was no significant effect observed on hospital admissions related to heart failure or on the composite outcome of cardiovascular death or hospitalization for heart failure. The subgroup analyses showed consistent benefits across patient groups, including those with or without T2D.
The authors highlight that the findings support the broader adoption of SGLT-2 inhibitors in clinical practice for patients with HFrEF. The results align with clinical trial evidence, reinforcing the drugs’ role in reducing mortality and emphasizing their effectiveness in diverse, real-world patient populations.
“These results support the benefits of SGLT-2 inhibitors observed in randomized controlled trials and provide novel and important data on their effectiveness in real-world clinical settings and across key clinical subgroups, including patients with and without diabetes,” Svanström and colleagues concluded.
Expert peer commentary
An editorial accompanying the study by Veena Manja of the VA Northern California Healthcare System and the University of California, Davis, along with Paul Heidenreich of the VA Palo Alto Healthcare System and Stanford University, underscored the importance of validating the analysis’ findings against clinical trial results. They noted discrepancies in the study such as the greater observed reduction in mortality but lack of impact on hospitalizations.
“In spite of these limitations, these results provide assurance that no unexpected harm results from SGLT-2 inhibitors when they are used for treatment of heart failure outside the clinical trial setting” the authors of the editorial noted. ■