Abstract 17027: Generalizability of the US FDA Label for Dapagliflozin to Patients With Heart Failure With Reduced Ejection Fraction in the GWTG-HF Registry

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Muthiah Vaduganathan ◽  
Stephen Greene ◽  
Shuaiqi Zhang ◽  
maria v grau-sepulveda ◽  
Adam D Devore ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Ejection Fraction ◽  
Care Facility ◽  
Eligibility Criteria ◽  
Discharge Data ◽  
Reduced Ejection Fraction ◽  
Type 2 Dm ◽  
The Us ◽  
Us Fda

Background: In May 2020, dapagliflozin was approved by the US FDA as the first SGLT-2 inhibitor for HF with reduced ejection fraction (HFrEF) based on the pivotal DAPA-HF trial. Limited data are available characterizing its generalizability to US clinical practice. Methods: We studied patients with HFrEF (≤40%) hospitalized at 406 sites in the Get With The Guidelines (GWTG)-HF registry admitted between Jan 2014 - Sept 2019. We excluded patients who left against medical advice, transferred to an acute care facility or to hospice, or had missing critical data. We applied the FDA label (excluding eGFR<30 mL/min/1.73 m 2 , dialysis, or type 1 DM) and eligibility criteria of DAPA-HF to the GWTG-HF registry sample. Results: Among 154,714 patients hospitalized with HFrEF, 125,497 (81.1%) would be candidates for dapagliflozin under the FDA label. Across 355 sites with ≥10 hospitalizations, median proportion of FDA label candidates was 81.1% (77.8%-84.6%). This proportion was similar across all study years (80.4-81.7%) and higher among those without type 2 DM than with type 2 DM (85.5% vs. 75.6%). Among GWTG-HF participants, the most frequent reason for not meeting the FDA label was eGFR<30 mL/min/1.73 m 2 (n=28,605). Among patients with available paired admission and discharge data, 14.2% had eGFR<30 mL/min/1.73 m 2 at both time points, while 3.8% developed eGFR<30 mL/min/1.73 m 2 by discharge. While there were more women, more Black patients, and less Asian patients in GWTG-HF, clinical characteristics were qualitatively similar between DAPA-HF trial and GWTG-HF registry participants. Compared with the DAPA-HF trial cohort, there was lower use of evidence-based HF therapies among GWTG-HF patients ( Table ). Conclusions: These data from a large, contemporary US hospitalized HF registry suggest that 4 out of 5 patients with HFrEF (with or without type 2 DM) would be candidates for initiation of dapagliflozin, and support its broad generalizability to US clinical practice.

Evaluation of dapagliflozin in the treatment of heart failure

2020 ◽  
Author(s):  
Sara Sotirakos
Keyword(s):  
Heart Failure ◽  
New York ◽  
Sglt2 Inhibitor ◽  
Heart Association ◽  
Reduced Ejection Fraction ◽  
The Us ◽  
New York Heart Association ◽  
Us Fda ◽  
European Society Of Cardiology

The European Society of Cardiology recently addressed the use of SGLT2 inhibitor use in the treatment of heart failure (HF). Dapagliflozin is a SGLT2 inhibitor recently approved by the US FDA for treatment of patients with HF with a reduced ejection fraction with a New York Heart Association classification of II–IV. Dapagliflozin significantly decreases the risk of worsening HF or death from cardiovascular cause compared with placebo and this risk does not differ based on the presence or absence of Type 2 diabetes. This paper aims to summarize the chemistry, pharmacodynamics and pharmacokinetics of dapagliflozin; and evaluates the clinical efficacy of dapagliflozin in the treatment of HF.

scholarly journals Gap between guidelines and clinical practice in heart failure with reduced ejection fraction: Results from TSOC-HFrEF registry

2017 ◽  
Vol 80 (12) ◽  
pp. 750-757 ◽  
Author(s):  
Hung-Yu Chang ◽  
Chun-Chieh Wang ◽  
Jeng Wei ◽  
Chong-Yi Chang ◽  
Yi-Cheng Chuang ◽  
...  
Keyword(s):  
Heart Failure ◽  
Clinical Practice ◽  
Ejection Fraction ◽  
Reduced Ejection Fraction

scholarly journals MR-proANP and incident cardiovascular disease in patients with type 2 diabetes with and without heart failure with preserved ejection fraction

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Jesper Jensen ◽  
Morten Schou ◽  
Caroline Kistorp ◽  
Jens Faber ◽  
Tine W. Hansen ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Ejection Fraction ◽  
Natriuretic Peptides ◽  
Continuous Variable ◽  
Preserved Ejection Fraction ◽  
Reduced Ejection Fraction ◽  
Increased Risk ◽  
Definition Of

Abstract Background Mid-regional pro-atrial natriuretic peptide (MR-proANP) is a useful biomarker in outpatients with type 2 diabetes (T2D) to diagnose heart failure (HF). Elevated B-type natriuretic peptides are included in the definition of HF with preserved ejection fraction (HFpEF) but little is known about the prognostic value of including A-type natriuretic peptides (MR-proANP) in the evaluation of patients with T2D. Methods We prospectively evaluated the risk of incident cardiovascular (CV) events in outpatients with T2D (n = 806, mean ± standard deviation age 64 ± 10 years, 65% male, median [interquartile range] duration of diabetes 12 [6–17] years, 17.5% with symptomatic HFpEF) according to MR-proANP levels and stratified according to HF-status including further stratification according to a prespecified cut-off level of MR-proANP. Results A total of 126 CV events occurred (median follow-up 4.8 [4.1–5.3] years). An elevated MR-proANP, with a cut-off of 60 pmol/l or as a continuous variable, was associated with incident CV events (p < 0.001). Compared to patients without HF, patients with HFpEF and high MR-proANP (≥ 60 pmol/l; median 124 [89–202] pmol/l) and patients with HF and reduced ejection fraction (HFrEF) had a higher risk of CV events (multivariable model; hazard ratio (HR) 2.56 [95% CI 1.64–4.00] and 3.32 [1.64–6.74], respectively). Conversely, patients with HFpEF and low MR-proANP (< 60 pmol/l; median 46 [32–56] pmol/l) did not have an increased risk (HR 2.18 [0.78–6.14]). Conclusions Patients with T2D and HFpEF with high MR-proANP levels had an increased risk for CV events compared to patients with HFpEF without elevated MR-proANP and compared to patients without HF, supporting the use of MR-proANP in the definition of HFpEF from a prognostic point-of-view.

scholarly journals Efficacy of Dapagliflozin on Renal Function and Outcomes in Patients with Heart Failure with Reduced Ejection Fraction: Results of DAPA-HF

Circulation ◽  
2020 ◽  
Author(s):  
Pardeep S. Jhund ◽  
Scott D. Solomon ◽  
Kieran F. Docherty ◽  
Hiddo J.L. Heerspink ◽  
Inder S. Anand ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Kidney Function ◽  
Adverse Outcomes ◽  
Renal Outcome ◽  
Pharmacological Management ◽  
Reduced Ejection Fraction ◽  
Patients With Heart Failure ◽  
Rate Of Decline

Background: Many patients with heart failure and reduced ejection fraction (HFrEF) have chronic kidney disease (CKD) which complicates pharmacological management and is associated with worse outcomes. We assessed the safety and efficacy of dapagliflozin in patients with HFrEF, according to baseline kidney function, in the Dapagliflozin and Prevention of Adverse-outcomes in Heart Failure trial (DAPA-HF). We also examined the effect of dapagliflozin on kidney function after randomization. Many patients with heart failure and reduced ejection fraction (HFrEF) have chronic kidney disease (CKD) which complicates pharmacological management and is associated with worse outcomes. We assessed the safety and efficacy of dapagliflozin in patients with HFrEF, according to baseline kidney function, in the Dapagliflozin and Prevention of Adverse-outcomes in Heart Failure trial (DAPA-HF). We also examined the effect of dapagliflozin on kidney function after randomization. Methods: HFrEF patients with or without type 2 diabetes and an estimated glomerular filtration rate (eGFR) ≥30 ml/min/1.73m 2 were enrolled in DAPA-HF. We calculated the incidence of the primary outcome (CV death or worsening HF) according to eGFR category at baseline (<60 and ≥60 ml/min/1.73m 2 ) as well as using eGFR at baseline as a continuous measure. Secondary cardiovascular outcomes and a pre-specified composite renal outcome (≥ 50% sustained decline eGFR, end stage renal disease (ESRD) or renal death) were also examined, along with decline in eGFR over time. Results: Of 4742 with a baseline eGFR, 1926 (41%) had eGFR <60 ml/min/1.73m 2 . The effect of dapagliflozin on the primary and secondary outcomes did not differ by eGFR category or examining eGFR as a continuous measurement. The hazard ratio (95% confidence interval (CI)) for the primary endpoint in patients with CKD was 0.71 (0.59, 0.86) vs. 0.77 (0.64, 0.93) in those with an eGFR ≥60 ml/min/1.73m 2 (interaction p=0.54). The composite renal outcome was not reduced by dapagliflozin (HR=0.71, 95% CI 0.44, 1.16; p=0.17) but the rate of decline in eGFR between day 14 and 720 was less with dapagliflozin, -1.09 (-1.41, -0.78) vs. placebo -2.87 (-3.19, -2.55) ml/min/1.73m 2 per year (p<0.001). This was observed in those with and without type 2 diabetes (p for interaction=0.92) Conclusions: Baseline kidney function did not modify the benefits of dapagliflozin on morbidity and mortality in HFrEF and dapagliflozin slowed the rate of decline in eGFR, including in patients without diabetes. Clinical Trial Registration: https://clinicaltrials.gov Unique Identifier: NCT03036124

Sign in / Sign up

Export Citation Format

Share Document