Meeting NewsPerspective

Dapagliflozin may improve lung fluid volume in HF

Mikhail Kosiborod

PHILADELPHIA — Treatment with the SGLT2 inhibitor dapagliflozin was not associated with a reduction in mean lung fluid volume among adults with HF with reduced ejection fraction compared with placebo.

However, a greater proportion of dapagliflozin-treated patients experienced an improvement in lung fluid volume at 12 weeks, according to a new subgroup analysis of the DEFINE-HF trial.

“To our knowledge, this is the first study to demonstrate a direct effect of dapagliflozin — or any SGLT2 inhibitor for that matter — on more effective decongestion, by looking at actual fluid in the lungs,” Mikhail Kosiborod, MD, FACC, FAHA, cardiologist at Saint Luke’s Mid America Heart Institute and professor of medicine at the University of Missouri-Kansas City School of Medicine, said during a moderated poster session at the American Heart Association Scientific Sessions. “Patients with a decrease in lung fluid volume, independent of treatment assignment, experienced declines in natriuretic peptides and large improvements in Kansas City Cardiomyopathy Questionnaire (KCCQ) clinical summary score. This is the first effort to correlate noninvasive assessments of lung fluid volume with HF biomarkers and health status.”

As Healio previously reported, the DEFINE-HF trial demonstrated that treatment with dapagliflozin (Farxiga, AstraZeneca) was associated with clinically meaningful improvements in HF-related health status or N-terminal pro-B-type natriuretic peptide levels at 12 weeks in patients with HFrEF with or without diabetes.

Treatment with the SGLT2 inhibitor dapagliflozin was not associated with a reduction in mean lung fluid volume among adults with HF with reduced ejection fraction compared with placebo.
Source: Healio

For DEFINE-HF, researchers randomly assigned 263 patients with LVEF 40% or less, NYHA class II or III status, estimated glomerular filtration rate at least 30 mL/min/1.73 m2 and elevated natriuretic peptides to dapagliflozin 10 mg daily or placebo.

Within the cohort, 85 participants (41 assigned dapagliflozin; 44 assigned placebo) agreed to participate in a substudy measuring lung fluid volume with remote dielectric sensing (ReDS, Sensivest), a noninvasive method to measure absolute percentage of lung fluid volume at baseline and 12 weeks (normal range, 20% to 35%). Baseline lung fluid volume was 34%. Substudy outcomes included mean lung fluid volume and proportion of patients with an improvement or no change or a deterioration in lung fluid volume, adjusting for baseline lung fluid volume, age, estimated glomerular filtration rate and diabetes status.

At 12 weeks, researchers observed no difference in mean adjusted lung fluid volume with dapagliflozin compared with placebo (34% vs. 35%; P = .3). However, fewer dapagliflozin-treated patients experienced no change or a deterioration in lung fluid volume (47% vs. 63%), and a greater proportion of dapagliflozin-treated patients experienced an improvement in lung fluid volume compared with the placebo group (53% vs. 37%; overall P = .04), Kosiborod said.

Additionally, participants who experienced an improvement in lung fluid volume had a numerically greater reduction in NT-proBNP level compared with those who had no change in lung fluid volume (mean, –439 pg/mL vs. –47 pg/mL; P = .2), as well as a greater decrease in BNP level (mean, –143 pg/mL vs. –18 pg/mL, P = .01), and a greater improvement in HF-specific symptoms and functional status as assessed by KCCQ clinical summary score (mean, 5.5 points vs. –2.8 points; P = .005). – by Regina Schaffer

Reference:

Kosiborod MN, et al. Abstract MDP473. Presented at: American Heart Association Scientific Sessions; Nov. 16-18, 2019; Philadelphia.

Disclosure: Kosiborod reports he has received grants, honoraria and other research support from Amarin, Amgen, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Eisai, Eli Lilly, GlaxoSmithKline, Glytec, Janssen, Merck, Novartis, Novo Nordisk and Sanofi.

Mikhail Kosiborod

PHILADELPHIA — Treatment with the SGLT2 inhibitor dapagliflozin was not associated with a reduction in mean lung fluid volume among adults with HF with reduced ejection fraction compared with placebo.

However, a greater proportion of dapagliflozin-treated patients experienced an improvement in lung fluid volume at 12 weeks, according to a new subgroup analysis of the DEFINE-HF trial.

“To our knowledge, this is the first study to demonstrate a direct effect of dapagliflozin — or any SGLT2 inhibitor for that matter — on more effective decongestion, by looking at actual fluid in the lungs,” Mikhail Kosiborod, MD, FACC, FAHA, cardiologist at Saint Luke’s Mid America Heart Institute and professor of medicine at the University of Missouri-Kansas City School of Medicine, said during a moderated poster session at the American Heart Association Scientific Sessions. “Patients with a decrease in lung fluid volume, independent of treatment assignment, experienced declines in natriuretic peptides and large improvements in Kansas City Cardiomyopathy Questionnaire (KCCQ) clinical summary score. This is the first effort to correlate noninvasive assessments of lung fluid volume with HF biomarkers and health status.”

As Healio previously reported, the DEFINE-HF trial demonstrated that treatment with dapagliflozin (Farxiga, AstraZeneca) was associated with clinically meaningful improvements in HF-related health status or N-terminal pro-B-type natriuretic peptide levels at 12 weeks in patients with HFrEF with or without diabetes.

Treatment with the SGLT2 inhibitor dapagliflozin was not associated with a reduction in mean lung fluid volume among adults with HF with reduced ejection fraction compared with placebo.
Source: Healio

For DEFINE-HF, researchers randomly assigned 263 patients with LVEF 40% or less, NYHA class II or III status, estimated glomerular filtration rate at least 30 mL/min/1.73 m2 and elevated natriuretic peptides to dapagliflozin 10 mg daily or placebo.

Within the cohort, 85 participants (41 assigned dapagliflozin; 44 assigned placebo) agreed to participate in a substudy measuring lung fluid volume with remote dielectric sensing (ReDS, Sensivest), a noninvasive method to measure absolute percentage of lung fluid volume at baseline and 12 weeks (normal range, 20% to 35%). Baseline lung fluid volume was 34%. Substudy outcomes included mean lung fluid volume and proportion of patients with an improvement or no change or a deterioration in lung fluid volume, adjusting for baseline lung fluid volume, age, estimated glomerular filtration rate and diabetes status.

At 12 weeks, researchers observed no difference in mean adjusted lung fluid volume with dapagliflozin compared with placebo (34% vs. 35%; P = .3). However, fewer dapagliflozin-treated patients experienced no change or a deterioration in lung fluid volume (47% vs. 63%), and a greater proportion of dapagliflozin-treated patients experienced an improvement in lung fluid volume compared with the placebo group (53% vs. 37%; overall P = .04), Kosiborod said.

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Additionally, participants who experienced an improvement in lung fluid volume had a numerically greater reduction in NT-proBNP level compared with those who had no change in lung fluid volume (mean, –439 pg/mL vs. –47 pg/mL; P = .2), as well as a greater decrease in BNP level (mean, –143 pg/mL vs. –18 pg/mL, P = .01), and a greater improvement in HF-specific symptoms and functional status as assessed by KCCQ clinical summary score (mean, 5.5 points vs. –2.8 points; P = .005). – by Regina Schaffer

Reference:

Kosiborod MN, et al. Abstract MDP473. Presented at: American Heart Association Scientific Sessions; Nov. 16-18, 2019; Philadelphia.

Disclosure: Kosiborod reports he has received grants, honoraria and other research support from Amarin, Amgen, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Eisai, Eli Lilly, GlaxoSmithKline, Glytec, Janssen, Merck, Novartis, Novo Nordisk and Sanofi.

    Perspective

    Prior large trials have demonstrated reductions in the risk for HF-related hospitalizations with SGLT2 inhibitors in people with type 2 diabetes. The DEFINE-HF trial randomly assigned 263 patients with a prior diagnosis of class II or III congestive HF with and without type 2 diabetes already on optimal medical therapy for HF to dapagliflozin 10 mg vs. placebo for 12 weeks, and demonstrated improvements in HF symptoms and biomarkers in the treatment group. A subgroup was studied to determine if reduction in lung fluid volume could account for this. Using noninvasive “vest” technology, the researchers confirmed that participants who experienced greater symptom improvement and lower biomarkers, such as levels of BNP and NT-proBNP, had reduced lung fluid volume, suggesting this was the mechanism.

    The DEFINE-HF trial, along with the recent DAPA-HF trial, places dapagliflozin, and possibly the other SGLT2 inhibitors, as an ideal, first-line treatment option for patients with type 2 diabetes and a history of HF or those at high risk for HF needing glycemic management. The findings also open the door for the potential use of these agents as add-on to standard HF therapy in patients with HF without diabetes.

    • Elise Brett, MD
    • Assistant Clinical Professor
      Division of Endocrinology, Diabetes and Bone Disease
      Icahn School of Medicine at Mount Sinai

    Disclosures: Brett reports no relevant financial disclosures.

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