medwireNews: Sodium-glucose cotransporter (SGLT)2 inhibitors reduce the risk for adverse outcomes in a broad range of patients with heart failure (HF), suggest findings from a meta-analysis of five randomized placebo-controlled trials.
“Despite the differences in patient populations and study designs, the evidence is strikingly consistent and resoundingly clear—SGLT2 inhibitors are the bedrock of therapy for heart failure regardless of ejection fraction or care setting,” say the authors of a comment accompanying the research published in The Lancet.
The study, which was also presented at the European Society of Cardiology conference in Barcelona, Spain, comprised a prespecified meta-analysis of DELIVER and EMPEROR-Preserved – two trials of SGLT2 inhibitors in patients with HF and preserved or mildly reduced ejection fraction – as well as a larger post-hoc meta-analysis including trials of these agents in patients with HF and reduced ejection fraction. Median follow-up time ranged from 9 months to 2.3 years.
Scott Solomon (Brigham and Women’s Hospital, Boston, Massachusetts, USA) and co-investigators found that among a total of 12,251 participants from DELIVER and EMPEROR-Preserved, SGLT2 inhibition with dapagliflozin or empagliflozin reduced the risk for cardiovascular (CV) death or first hospitalization for HF relative to placebo, with a significant hazard ratio (HR) of 0.80.
These findings remained consistent when these endpoints were analyzed separately, with an HR of 0.88 for CV death and 0.74 for first HF hospitalization.
The team then evaluated these data in combination with two trials involving participants with HF and reduced ejection fraction – DAPA-HF and EMPEROR-Reduced – as well as those hospitalized with worsening HF regardless of ejection fraction in the SOLOIST-WHF trial.
In this broader meta-analysis (n=21,947), SGLT2 inhibitors significantly reduced the risk for CV death or HF hospitalization (HR=0.77), with a number needed to treat of 25 to prevent one event during a weighted mean of 23 months.
And this result was consistent across the majority of subgroups studied, including people with and without diabetes, across categories of BMI and kidney function, and in those with and without mineralocorticoid receptor antagonist or angiotensin receptor neprilysin inhibitor use.
Commentators Katherine Tuttle (Providence Medical Research Center, Spokane, Washington, USA) and Janani Rangaswami (George Washington University School of Medicine, Washington DC, USA) say that the strengths of these analyses “include large sample sizes and use of different agents, making the case for generalisability across the SGLT2 inhibitor class.”
They note, however, that “demographic representation remains problematic in these studies,” with “woefully small” participant numbers from non-White and non-Asian groups.
“[C]oncerted efforts should be made to find study sites that enrol Black and other groups at high risk,” they add.
Tuttle and Rangaswami conclude: “The next frontier is to equitably implement SGLT2 inhibitors, and other therapies, by overcoming barriers to delivery of optimal care.”
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