Heart failure remains a major public health disease with high morbidity and mortality, and it is the leading cause of hospitalizations in older patients (>65 years). The role of sodium-glucose cotransporter 2 inhibitors (SGLT2i) is now well-established in patients with heart failure and diabetes mellitus. However, their efficacy and safety in heart failure patients without diabetes remains unclear. Therefore, we conducted a meta-analysis of randomized controlled trials (RCTs) to evaluate the role of SGLT2i in this vulnerable population.
A comprehensive search of electronic database was performed. Two investigators (MM, SS) screened the trials and extracted the data independently. The primary outcome of interest was a composite of cardiovascular death and heart failure hospitalizations. The secondary outcome was the quality-of-life (QoL) improvement as measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ). We calculated odds ratios (ORs) and mean differences (MDs) with their 95% confidence intervals (CIs) for dichotomous and continuous data, respectively, using a random-effects model.
We identified 4 RCTs included 7,168 patients (mean age 66.3 ± 11.0 years, 37.1% were females, and 46.5% were non-Caucasians) with a mean follow up of 14.5 ± 5.0 months. Only one trial was exclusively in heart failure patients without diabetes, and the other 3 RCTs included patients with and without diabetes, for which we extracted data from the nondiabetics patients. , , The mean left ventricular ejection fraction (LVEF) was 30% ± 6.8% (83.5% with ischemic cardiomyopathy) and the mean eGFR was 66 ± 20 ml/min/1.73 m 2 . Compared with the placebo group, SGLT2i was associated with a significant reduction of the primary composite outcome (OR = 0.71; 95% CI = 0.63 to 0.81; p <0.01) and a significant improvement in the KCCQ (MD = 5.37; 95% CI = 0.73 to 10.0; p = 0.02; Figure 1 ).
In this study of patients with heart failure without diabetes, we found that SGLT2i was associated with a significant reduction of cardiovascular mortality and heart failure hospitalization. In addition, SGLT2i was associated with a significant improvement in QoL as measured by the KCCQ.
In patients with diabetes mellitus and heart failure, SGLT2i was associated with a decreased risk of clinically relevant cardiovascular death, heart failure hospitalization, and heart failure symptoms. In our investigation, we found that SGLT2i administered to non-diabetic heart failure is associated improved clinical outcomes. These findings suggest that the benefits of SGLT2i are independent of glucose lowering effects. Although the beneficial effects of SGLT2i were thought to be due to its diuretic effects, recent trials showed favorable effects on myocardial remodeling.
Limitations of this study are mainly due to small sample size, relatively short follow-up duration, and limited trials of exclusively heart failure patients without diabetes. Further larger RCTs with long-term follow-up are needed.
In conclusion, among heart failure patients without diabetes, SGLT2i was associated with a significant reduction of cardiovascular mortality and heart failure hospitalization as well as improvements in QoL.
Disclosures
The authors report no competing interests.
References
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