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Dapagliflozin in Heart Failure With Preserved Ejection Fraction

In patients with heart failure with preserved ejection fraction (HFpEF), dapagliflozin reduced resting and exercise pulmonary capillary wedge pressure (PCWP) and had favorable effects on plasma volume and body weight, researchers report. “These findings provide new insight into the hemodynamic mechanisms of benefit with sodium-glucose cotransporter-2 inhibitors in HFpEF,” the authors add.

The single-center, double-blinded, randomized, placebo-controlled trial included patients with New York Heart Association class II or III heart failure, ejection fraction of 50% or more, and elevated PCWP during exercise. To test the effects of dapagliflozin 10 mg, cardiac hemodynamics were measured at rest and during exercise using high-fidelity micromanometers at baseline and after 24 weeks of treatment.

“Among 38 patients completing baseline assessments (median age 68 years; 66% women; 71% obese), 37 completed the trial. Treatment with dapagliflozin resulted in reduction in the primary end point of change in PCWP at rest and during exercise at 24 weeks relative to treatment with placebo (likelihood ratio test for overall changes in PCWP; P<0.001), with lower PCWP at rest (estimated treatment difference [ETD], −3.5 mm Hg [95% CI, −6.6 to −0.4]; P=0.029) and maximal exercise (ETD, −5.7 mm Hg [95% CI, −10.8 to −0.7]; P=0.027). Body weight was reduced with dapagliflozin (ETD, −3.5 kg [95% CI, −5.9 to −1.1]; P=0.006), as was plasma volume (ETD, −285 mL [95% CI, −510 to −60]; P=0.014), but there was no significant effect on red blood cell volume. There were no differences in oxygen consumption at 20-W or peak exercise, but dapagliflozin decreased arterial lactate at 20 W (−0.70 ± 0.77 versus 0.37 ± 1.29 mM; P=0.006).”

Source: Circulation