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29-03-2021 | Empagliflozin | News

Diuresis ‘not dominant’ mediator of SGLT2 inhibitors’ cardiac benefits

Eleanor McDermid

medwireNews: Empagliflozin has similar cardioprotective effects in people with heart failure regardless of whether or not they have recent volume overload, report the EMPEROR-Reduced investigators.

Several recent studies have demonstrated a fluid reduction effect of sodium-glucose cotransporter (SGLT)2 inhibition in people with heart failure, and the authors of the current study note that their findings “do not negate the possibility that SGLT2 inhibitors may exert effects on urine volume or composition or on fluid compartments in the body.”

But they found that people with clinical evidence of recent volume overload “do not exhibit an exaggerated benefit with SGLT2 inhibitors, even during short-term treatment,” suggesting that the diuretic effect of the treatment class is not the major mechanism underpinning its cardioprotective effects.

Almost 40% of the 3730 EMPEROR-Reduced trial participants (none of whom had diabetes) had recent volume overload, as determined by study site investigators at enrollment.

“Because there is no consensus on the definition of euvolemia, no guidance was provided to investigators on how to identify patients with volume overload,” the researchers note.

Participants with volume overload were more likely than those without to have recent worsening of heart failure symptoms, heart failure hospitalization, and treatment with an intravenous diuretic. They more often had severe symptoms and had a significant 1.31-fold higher likelihood for experiencing a primary outcome event of cardiovascular death or heart failure hospitalization during the trial.

These participants’ clinical features and treatment history suggest “a degree of diuretic resistance, a finding supported by the lower values of serum chloride in these patients,” write Milton Packer (Baylor University Medical Center, Dallas, Texas, USA) and co-researchers in the Journal of the American College of Cardiology.

Nevertheless, this subgroup derived similar, or even slightly less, benefit from empagliflozin treatment than people without volume overload. The SGLT2 inhibitor reduced the risk for the primary outcome by 19% and 29% in the two groups, respectively, and for total heart failure hospitalizations by a corresponding 16% and 40%.

Moreover, “the benefits of empagliflozin seemed to emerge more rapidly in patients without recent volume overload,” say Packer et al.

And the two groups obtained similar treatment benefits for other endpoints, such as diuretic use, heart failure symptoms, and indicators of volume, such as natriuretic peptides, systolic blood pressure, and serum albumin.

The researchers conclude that, “taken together, our findings do not support a dominant role of diuresis in mediating the physiological changes or clinical benefits of SGLT2 inhibitors on the course of heart failure in patients with a reduced ejection fraction.”

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2021 Springer Healthcare Ltd, part of the Springer Nature Group

J Am Coll Cardiol 2021; 77: 1381–1392