Data suggest ‘crystal-clear class effect’ for SGLT2 inhibitor benefits in HF
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An analysis of 13 randomized controlled trials of SGLT2 inhibitors showed the class reduced CV death, HF hospitalization and serious adverse events in people with HF, according to data published in The American Journal of Cardiology.
“SGLT2 inhibitors were historically known as antidiabetic drugs, but with accumulating evidence from randomized controlled trials, we now are confident about their safety and efficacy in HF and chronic kidney disease, with and without type 2 diabetes,” Ahmed Bendary, MD, FESC, associate professor of cardiovascular medicine at Benha University, Egypt, told Healio. “We found that in patients with diabetes, SGLT2 inhibitors significantly reduced HF hospitalization, CV mortality and serious adverse events. However, in patients without diabetes, despite showing a significant reduction in HF hospitalization, SGLT2 inhibitors reduced CV mortality or serious adverse events, but without statistical significance.”
In a meta-analysis, Bendary and colleagues analyzed randomized controlled trial data from 13 studies that compared the effect of SGLT2 inhibitors vs. placebo in 75,287 adults with HF, stratified by diabetes status (41,054 participants in the SGLT2 inhibitor arms).
Researchers found that SGLT2 inhibitors significantly lowered risk for HF hospitalization in participants with type 2 diabetes (RR = 0.68; 95% CI, 0.63-0.74) and without type 2 diabetes (RR = 0.75; 95% CI, 0.62-0.89). SGLT2 inhibition was also associated with reduced mortality risk in participants’ diabetes (RR = 0.87; 95% CI, 0.77-0.99); however, this finding did not rise to statistical significance in participants without diabetes (RR = 0.93; 95% CI, 0.7-1.23).
SGLT2 inhibitors also lowered risk for serious adverse events among participants with diabetes (RR = 0.94; 95% CI, 0.9-0.98) and without diabetes (RR = 0.72; 95% CI, 0.38-1.39).
“The current analysis might have been underpowered for the outcome of CV death in patients without diabetes, due to the small number of trials reporting this outcome separately in the nondiabetic population,” Bendary told Healio. “Nevertheless, across all randomized controlled trials, for all SGLT2 inhibitors, there was no evidence on significant interaction for the composite primary outcome based on the glycemic status. However, when you start looking specifically at the endpoint of CV death, some heterogenous treatment effect based on the glycemic status emerges, albeit with statistical caveats.
“The findings of this meta-analysis, among others, are undoubtedly setting the stage for a crystal-clear class effect of SGLT2 inhibitors on safe and effective improvement of HF outcomes across the ejection fraction and glycemic spectrums,” Bendary told Healio. “This is a new chapter in the HF therapeutic armamentarium.”
Bendary said more research is needed exploring the effects of SGLT2 inhibitors in people with HF with preserved EF, especially those without diabetes.
Reference:
Ahmed Bendary, MD, FESC, can be reached at ahmed.bendari@fmed.bu.edu.eg.
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