Evaluation Of The Mechanism Of Benefit For Dapagliflozin In Heart Failure With Preserved Ejection Fraction: An Invasive Hemodynamic Randomized Trial

Presented at the ACC.23 by: Barry Borlaug, MD - Rochester, MN, USA

Introduction and methods

Recent RCTs showed that SGLT2i treatment reduced the risk of HF hospitalization and CV death and improve quality of life in patients with HFpEF, but the mechanisms behind these benefits remain unclear. A fundamental pathophysiological feature of HFpEF is elevation of left heart filling pressures at rest and during exercise.

In the CAMEO-DAPA (Evaluation of the Cardiac and Metabolic Effects of Dapagliflozin in Heart Failure With Preserved Ejection Fraction) trial, a single-center, double-blind, phase II RCT, the effect of treatment with dapagliflozin 10 mg once daily for 24 weeks versus placebo on rest and exercise left heart filling pressures was evaluated in a total of 38 HFpEF patients (LVEF ≥50%; NYHA class 2–3 HF symptoms; pulmonary capillary wedge pressure (PCWP) ≥25 mmHg during exercise).

The primary endpoint was change in PCWP between baseline and 24 weeks incorporating rest and exercise measurements. Key secondary endpoints were rest/exercise right atrial (RA) and pulmonary arterial (PA) pressures; directly measured plasma, total blood, and red-cell volumes; and body weight.

Main results

• Compared with placebo-treated patients, dapagliflozin-treated patients showed a larger decrease in PCWP from baseline, both at rest (∆ absolute difference: –3.5 mmHg; 95%CI: –6.7 to –0.4; P=0.029) and during exercise (∆ absolute difference: –6.1 mmHg; 95%CI: –11.2 to –1.0; P=0.019) (likelihood-ratio test in overall linear mixed model: P<0.001).
• Although dapagliflozin had no effect on change in RA pressure or mean PA pressure at rest (both P>0.05), it did lower both RA pressure (treatment effect estimate: –4.2 mmHg; 95%CI: –7.3 to –1.0; P=0.010) and mean PA pressure (treatment effect estimate: –5.9 mmHg; 95%CI: –10.9 to –0.9; P=0.022) during exercise compared with placebo.
• After 24 weeks, body weight (treatment effect estimate: –3.5 kg; 95%CI: –5.9 to –1.1; P=0.006) and plasma volume (treatment effect estimate: –285 mL; 95%CI: –510 to –60; P=0.015) were decreased in the dapagliflozin group compared with the placebo group. However, there was no difference between the groups in change in total blood or red-cell volume (both P>0.05).
• Change in body weight at 24 weeks was related to change in PCWP at rest (r=0.51; P=0.001) and during exercise (r=0.43; P=0.009).

Conclusion

In HFpEF patients, 24-week treatment with dapagliflozin reduced PCWP at rest and during exercise compared with placebo. Dapagliflozin also reduced RA and PA pressures, body weight, and plasma volume.

• Our reporting is based on the information provided at the ACC.23 -