Dapagliflozin improves pulmonary capillary wedge pressure during exercise in HFpEF
Key takeaways:
- Dapagliflozin reduced left heart filling pressures at rest and during exercise in adults with HFpEF.
- The data provide new insight into mechanisms underlying the effects of dapagliflozin in HFpEF.
NEW ORLEANS — Treatment with the SGLT2 inhibitor dapagliflozin for 24 weeks favorably reduced pulmonary capillary wedge pressure at rest and during exercise in adults with HF with preserved ejection fraction vs. placebo, data show.
Elevated left heart filling pressures at rest and during exercise are a fundamental pathophysiologic feature of HFpEF that drive disability, worsen clinical status and lead to increased risk for adverse outcomes, Barry A. Borlaug, MD, consultant in the department of cardiovascular medicine at Mayo Clinic in Rochester, Minnesota, said during a featured clinical research presentation at the American College of Cardiology Scientific Session.
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“Our study shows that treatment with dapagliflozin for 24 weeks favorably reduced pulmonary capillary wedge pressure at rest and during exercise in patients with HFpEF, improving the fundamental hemodynamic abnormality underlying this disorder,” Borlaug said during the presentation.
In a single-center study, Borlaug and colleagues analyzed data from 37 adults with HFpEF with a pulmonary capillary wedge pressure (PCWP) greater than 25 mm Hg during exercise, randomly assigned to dapagliflozin (Farxiga, AstraZeneca) 10 mg once daily (n = 21) or placebo (n = 16) for 24 weeks. The mean age of participants was 67 years; 66% were women and 71% had obesity. At baseline and 24 weeks, participants underwent invasive exercise testing, hemodynamic assessments and measurements of total blood, plasma and red blood cell count volumes.
The primary endpoint was PCWP — a surrogate measure of left atrial pressure — incorporating measurements at rest and peak exercise. Secondary endpoints included right atrial and pulmonary arterial pressures at rest and during exercise; plasma, blood and red cell volumes; and body weight, all assessed at baseline and 24 weeks.
Within the cohort, mean PCWP was 33 mm Hg during exercise.
At 24 weeks, researchers observed no effect on wedge pressures during periods of rest or exercise compared with baseline for participants assigned placebo; however, participants assigned dapagliflozin experienced a mean 3.5 mm Hg reduction in resting wedge pressure, a 25% treatment effect reduction (95% CI, –6.7 to –0.4; P = .029). During exercise, there was a 6.1 mm Hg reduction (95% CI, –11.2 to –1; P = .019).
The overall mixed model likelihood ratio test to determine whether there was an overall effect of dapagliflozin vs. placebo, incorporating both rest and exercise, was highly significant (P < .001), Borlaug said.
Researchers observed trends for reductions in both mean right atrial and pulmonary arterial pressures at rest with dapagliflozin, becoming statistically significant during exercise, with a 4.2 mm Hg reduction in right atrial pressure (95% CI, –7.3 to –1; P = .01) and a 5.9 mm Hg reduction in mean pulmonary arterial pressure (95% CI, –10.9 to –0.9; P = .022).
There was an average 3.5 kg reduction in body weight among participants assigned dapagliflozin compared with placebo (95% CI, –5.9 to –1.1; P = .006). There was a trend but no significant change in total blood volume, but evidence of reduced plasma volume in the dapagliflozin group compared with the placebo group (treatment effect estimate, –285 mL; 95% CI, –510 to –60; P = .015), Borlaug said. Participants with a greater reduction in total body weight experienced a greater reduction in PCWP during rest (r = 0.51; P = .001) and during exercise (r = 0.43; P = .009).
The correlations with plasma volume “were much weaker than the relationships observed with total body weight,” Borlaug said.
Borlaug said the favorable hemodynamic changes seen with dapagliflozin were “tightly related” to reductions in body weight rather than changes in plasma volume.
“These findings provide new insight into the mechanisms underlying the favorable clinical effects of dapagliflozin in people with HFpEF,” Borlaug said.
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Borlaug BA, et al. Featured Clinical Research III. Presented at: American College of Cardiology Scientific Session; March 4-6, 2023; New Orleans (hybrid meeting).