scholarly journals Dapagliflozin and the Incidence of Type 2 Diabetes in Patients With Heart Failure and Reduced Ejection Fraction: An Exploratory Analysis From DAPA-HF

2020 ◽  
Author(s):  
Silvio E Inzucchi ◽  
Kieran F Docherty ◽  
Lars Køber ◽  
Mikhail N Kosiborod ◽  
Felipe A Martinez ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Ejection Fraction ◽  
Sglt2 Inhibitor ◽  
Adverse Outcomes ◽  
Exploratory Analysis ◽  
Diabetes Incidence ◽  
Reduced Ejection Fraction ◽  
Patients With Heart Failure

<b>Objective </b> <p>The SGLT2 inhibitor dapagliflozin reduced the risk of cardiovascular mortality and worsening heart failure in the <a>Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure </a>trial (DAPA-HF). This report explores the effect of dapagliflozin on incident type 2 diabetes in the non-diabetic cohort enrolled in the trial.</p> <p><b> </b></p> <p><b>Research Design/Methods</b></p> <p>The subgroup of 2605 patients with heart failure and reduced ejection fraction (HFrEF), no prior history of diabetes, and a HbA1c of <6.5% at baseline was randomized to dapagliflozin 10 mg daily or placebo. In this exploratory analysis, surveillance for new onset diabetes was accomplished through periodic HbA1c testing as part of the study protocol and comparison between the treatment groups assessed through a Cox proportional hazards model.</p> <p><b> </b></p> <p><b>Results</b></p> <p>At baseline, the mean HbA1c was 5.8%. At 8 months, there were minimal changes, with a placebo-adjusted change in the dapagliflozin group of -0.04%. Over a median follow-up of 18 months, diabetes developed in 93/1307 patients (7.1%) in the placebo group and 64/1298 (4.9%) in the dapagliflozin group. Dapagliflozin led to a 32% reduction in diabetes incidence (HR 0.68, 95% CI, 0.50-0.94; p=0.019.) More than 95% of the participants who developed type 2 diabetes had prediabetes at baseline (HbA1c 5.7-6.4%.) Participants who developed diabetes in DAPA-HF had a higher subsequent mortality than those who did not.</p> <p><b>Conclusions</b></p> <p>In this exploratory analysis among patients with HFrEF, treatment with dapagliflozin reduced the incidence of new diabetes. This potential benefit needs confirmation in trials of longer duration and in people without heart failure.</p>

scholarly journals Dapagliflozin and the Incidence of Type 2 Diabetes in Patients With Heart Failure and Reduced Ejection Fraction: An Exploratory Analysis From DAPA-HF

2020 ◽  
Author(s):  
Silvio E Inzucchi ◽  
Kieran F Docherty ◽  
Lars Køber ◽  
Mikhail N Kosiborod ◽  
Felipe A Martinez ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Ejection Fraction ◽  
Sglt2 Inhibitor ◽  
Adverse Outcomes ◽  
Exploratory Analysis ◽  
Diabetes Incidence ◽  
Reduced Ejection Fraction ◽  
Patients With Heart Failure

<b>Objective </b> <p>The SGLT2 inhibitor dapagliflozin reduced the risk of cardiovascular mortality and worsening heart failure in the <a>Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure </a>trial (DAPA-HF). This report explores the effect of dapagliflozin on incident type 2 diabetes in the non-diabetic cohort enrolled in the trial.</p> <p><b> </b></p> <p><b>Research Design/Methods</b></p> <p>The subgroup of 2605 patients with heart failure and reduced ejection fraction (HFrEF), no prior history of diabetes, and a HbA1c of <6.5% at baseline was randomized to dapagliflozin 10 mg daily or placebo. In this exploratory analysis, surveillance for new onset diabetes was accomplished through periodic HbA1c testing as part of the study protocol and comparison between the treatment groups assessed through a Cox proportional hazards model.</p> <p><b> </b></p> <p><b>Results</b></p> <p>At baseline, the mean HbA1c was 5.8%. At 8 months, there were minimal changes, with a placebo-adjusted change in the dapagliflozin group of -0.04%. Over a median follow-up of 18 months, diabetes developed in 93/1307 patients (7.1%) in the placebo group and 64/1298 (4.9%) in the dapagliflozin group. Dapagliflozin led to a 32% reduction in diabetes incidence (HR 0.68, 95% CI, 0.50-0.94; p=0.019.) More than 95% of the participants who developed type 2 diabetes had prediabetes at baseline (HbA1c 5.7-6.4%.) Participants who developed diabetes in DAPA-HF had a higher subsequent mortality than those who did not.</p> <p><b>Conclusions</b></p> <p>In this exploratory analysis among patients with HFrEF, treatment with dapagliflozin reduced the incidence of new diabetes. This potential benefit needs confirmation in trials of longer duration and in people without heart failure.</p>

scholarly journals Dapagliflozin and the Incidence of Type 2 Diabetes in Patients With Heart Failure and Reduced Ejection Fraction: An Exploratory Analysis From DAPA-HF

Diabetes Care ◽  
2020 ◽  
pp. dc201675
Author(s):  
Silvio E. Inzucchi ◽  
Kieran F. Docherty ◽  
Lars Køber ◽  
Mikhail N. Kosiborod ◽  
Felipe A. Martinez ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Ejection Fraction ◽  
Exploratory Analysis ◽  
Reduced Ejection Fraction ◽  
Patients With Heart Failure

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

scholarly journals Towards quadruple therapy for heart failure with reduced ejection fraction: DAPA-HF secondary analysis data

2020 ◽  
Vol 25 (5) ◽  
pp. 3870
Author(s):  
Zh. D. Kobalava ◽  
V. V. Medovchshikov ◽  
N. B. Yeshniyazov
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Sglt2 Inhibitor ◽  
Secondary Analysis ◽  
Analysis Data ◽  
Adverse Outcomes ◽  
Reduced Ejection Fraction ◽  
Sodium Glucose Cotransporter ◽  
Patients With Heart Failure ◽  
First Time

Patients with heart failure with reduced ejection fraction (HFrEF), despite optimal evidence-based treatment, have a high residual risk of adverse outcomes. The favorable results of studies on cardiovascular safety and the effectiveness of sodium-glucose cotransporter 2 (SGLT2) inhibitors in patients with type 2 diabetes (T2D), including outcomes associated with heart failure, were the reason for studying the effectiveness in patients with HFrEF regardless of the T2D status. For the first time in the DAPA-HF study, the SGLT2 inhibitor dapagliflozin in patients with HFrEF showed a positive effect on hard endpoints. Data of the secondary analysis confirmed the effectiveness of dapagliflozin regardless of the T2D status, therapy, age, and quality of life. The results of DAPA-HF have become a serious statement for changing the standards of the guideline-recommended therapy of HFrEF.

scholarly journals Effects of SGLT2 inhibitor dapagliflozin in patients with heart failure with reduced ejection fraction

2020 ◽  
Vol 25 (8) ◽  
pp. 4049
Author(s):  
N. R. Khasanov
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Drug Class ◽  
Sglt2 Inhibitor ◽  
Cardiovascular Death ◽  
Sglt2 Inhibitors ◽  
Reduced Ejection Fraction ◽  
Patients With Heart Failure ◽  
Recommended Therapy

SGLT2 inhibitors have been shown to reduce the risk of cardiovascular events and the development and decompensation of heart failure (HF) in patients with type 2 diabetes (T2D). The improved prognosis in HF may be related not only to the hypoglycemic effect of this drug class. The DAPA-HF study, which included patients with HF with reduced ejection fraction, demonstrated the benefit of dapagliflozin in reducing the risk of cardiovascular death and worsening HF, as well as improving HF symptoms compared to placebo, regardless of the presence of T2D and the recommended therapy for HF.

scholarly journals Effect of Empagliflozin on Left Ventricular Volumes in Patients with Type 2 Diabetes, or Prediabetes, and Heart Failure with Reduced Ejection Fraction (SUGAR-DM-HF)

Circulation ◽  
2020 ◽  
Author(s):  
Matthew M. Y. Lee ◽  
Katriona J. M. Brooksbank ◽  
Kirsty Wetherall ◽  
Kenneth Mangion ◽  
Giles Roditi ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Ejection Fraction ◽  
Global Longitudinal Strain ◽  
Sglt2 Inhibitor ◽  
Left Ventricular ◽  
Sglt2 Inhibitors ◽  
Reduced Ejection Fraction ◽  
B Lines

Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of heart failure hospitalization and cardiovascular death in patients with heart failure and reduced ejection fraction (HFrEF). However, their effects on cardiac structure and function in HFrEF are uncertain. Methods: We designed a multicenter randomized, double-blind, placebo-controlled trial to investigate the cardiac effects of empagliflozin in patients in NYHA functional class II to IV with a left ventricular (LV) ejection fraction ≤40% and type 2 diabetes or prediabetes. Patients were randomized 1:1 to empagliflozin 10 milligrams once daily or placebo, stratified by age (<65 and ≥65 years) and glycemic status (diabetes or prediabetes). The co-primary outcomes were change from baseline to 36 weeks in LV end-systolic volume indexed to body surface area (LVESVi) and LV global longitudinal strain (LV GLS) measured using cardiovascular magnetic resonance (CMR). Secondary efficacy outcomes included other CMR measures (LVEDVi, LVEF), diuretic intensification, symptoms (Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ-TSS)), 6-minute walk distance (6MWD), B-lines on lung ultrasound and biomarkers (including NT-proBNP). Results: From April 2018 to August 2019, 105 patients were randomized: 77 (73.3%) male, mean age 68.7 [SD 11.1] years, 82 (78.1%) diabetes and 23 (21.9%) prediabetes, mean LVEF 32.5% [9.8%], and 81 (77.1%) NYHA II and 24 (22.9%) NYHA III. Patients received standard treatment for HFrEF. Compared with placebo, empagliflozin reduced LVESVi by 6.0 (-10.8 to -1.2) ml/m 2 (p=0.015). There was no difference in LV GLS. Empagliflozin reduced LVEDVi by 8.2 (-13.7 to -2.6) ml/m 2 (p=0.0042) and reduced NT-proBNP by 28 (2 to 47) %, p=0.038. There were no between-group differences in other CMR measures, KCCQ-TSS, 6MWD or B-lines. Conclusions: The SGLT2 inhibitor empagliflozin reduced LV volumes in patients with HFrEF and type 2 diabetes or prediabetes. Favorable reverse LV remodeling may be a mechanism by which SGLT2 inhibitors reduce HF hospitalization and mortality in HFrEF. Clinical Trial Registration: URL: https://www.clinicaltrials.gov Unique Identifier: NCT03485092.

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