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

Inzucchi, Silvio E.; Docherty, Kieran F.; Køber, Lars; Kosiborod, Mikhail; Martínez, Felipe A.; Ponikowski, Piotr; Sabatine, Marc S.; Solomon, Scott D.; Verma, Subodh; Bělohlávek, Jan; Böhm, Michael; Chiang, Chern‐En; Boer, Rudolf A. de; Díez, Mirta; Dukát, Andre; Ljungman, Charlotta; Bengtsson, Olof; Langkilde, Anna Maria; Sjöstrand, Mikaela; Jhund, Pardeep S.; McMurray, John J.V.; Committees, DAPA-HF Investigators and

doi:10.2337/figshare.13235543

Cited by 8 publications

(11 citation statements)

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“…Importantly, the benefits of SGLT2i for HF were documented to be similar in patients with or without DM 45,46 . On the other hand, in HF and reduced ejection fraction, treatment with dapagliflozin can reduce the incidence of new DM and subsequent mortality 47 . These results are compelling and suggest the need for further assessment of the effects of SGLT2i on the progression of HF associated with prediabetes.…”

Section: Discussionmentioning

confidence: 98%

“…45,46 On the other hand, in HF and reduced ejection fraction, treatment with dapagliflozin can reduce the incidence of new DM and subsequent mortality. 47 These results are compelling and suggest the need for further assessment of the effects of SGLT2i on the progression of HF associated with prediabetes. The ongoing DANish randomized, double-blind, placebo-controlled trial in patients with chronic HEART failure (DANHEART) will provide important messages on the potential benefit and safety of metformin in patients with HF and with prediabetes.…”

Section: Discussionmentioning

confidence: 99%

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Association between prediabetes and adverse outcomes in heart failure

Mai

Wen

Qiu

et al. 2021

Diabetes Obesity Metabolism

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Aims Patients with heart failure (HF) and with diabetes experienced significantly worse outcomes than those without diabetes. However, data on the prognostic impact of prediabetes in HF are inconclusive. This meta‐analysis aimed to explore the association between prediabetes and the risk of all‐cause mortality and adverse cardiac outcomes in patients with HF. Materials and methods We searched multiple electronic databases (PubMed, Embase and Google Scholar) for relevant studies up to 31 March 2021. Studies were included for analysis if multivariable adjusted relative risks of adverse outcomes were reported in patients with prediabetes and with HF compared with those with normoglycaemia. Random‐effects models were used to calculate the pooled hazard ratios (HRs) and 95% confidence intervals (CIs). Results Twelve studies comprising 28 643 patients with HF reported the risk of all‐cause mortality and cardiac outcomes associated with prediabetes. The prevalence of prediabetes ranged from 9.6% to 37.2%. After a median follow‐up duration of 2.3 years, patients with HF and with prediabetes were associated with an increased risk of all‐cause mortality (HR 1.29, 95% CI 1.06‐1.58), cardiovascular mortality (HR 1.59, 95% CI 1.09‐2.32), HF hospitalization (HR 1.33, 95% CI 1.09‐1.61), all‐cause mortality and/or HF hospitalization (HR 1.22, 95% CI 1.01‐1.47), as well as cardiovascular mortality and/or HF hospitalization (HR 1.21, 95% CI 1.07‐1.37). Conclusions Prediabetes is associated with a worse prognosis in patients with HF. Further risk stratification and effective treatment strategies are needed in patients with prediabetes and with HF to improve the prognosis.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Association between prediabetes and adverse outcomes in heart failure

Mai

Wen

Qiu

et al. 2021

Diabetes Obesity Metabolism

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“…[27][28][29] Furthermore, a secondary analysis of the Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction (DAPA-HF) trial showed that dapagliflozin lowered the incidence of diabetes in patients with HF and reduced ejection fraction. 30 In addition to SGLT2i, catheter ablation emerged as another important prevention strategy for cardiovascular death and HHF in patients with AF. Catheter ablation was associated with significantly lower rates of HHF and death Diabetes, heart failure, and NT-proBNP in atrial fibrillation 2373 in patients with HF and an LVEF ≤35%.…”

Section: Discussionmentioning

confidence: 99%

Relationship of diabetes, heart failure, and N‐terminal pro‐B‐type natriuretic peptide with cardiovascular outcomes in patients with atrial fibrillation

Hofer

Pailer²,

Sulzgruber

et al. 2022

ESC Heart Failure

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Aims We aim to explore the relationship of heart failure (HF) and diabetes with cardiovascular (CV) death or hospitalization for HF (HHF) and to study the clinical utility of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in an unselected patient population with atrial fibrillation (AF). Methods and resultsPatients with AF admitted to a tertiary academic center between January 2005 and July 2019 were identified through a search of electronic health records. We used Cox regression models adjusted for age, sex, estimated glomerular filtration rate, diabetes, HF, body mass index, prior myocardial infarction, coronary artery disease, hypertension, smoking, C-reactive protein, and low-density lipoprotein cholesterol. To select the most informative variables, we performed a least absolute shrinkage and selection operator Cox regression with 10-fold cross-validation. In total, 7412 patients (median age 70 years, 39.7% female) were included in this analysis and followed over a median of 4.5 years. Both diabetes [adjusted (Adj.) HR 1.87, 95% CI 1.55-2.25] and HF (Adj. HR 2.57, 95% CI 2.22-2.98) were significantly associated with CV death/HHF after multivariable adjustment. Compared with patients with diabetes, HF patients had a higher risk of HHF but a similar risk of CV and all-cause death. NT-proBNP showed good discriminatory performance (area under the curve 0.78, 95% CI 0.77-0.80) and the addition of NT-proBNP to the covariates used for adjustment resulted in a significant area under the curve improvement (Δ = 0.04, P < 0.001). With least absolute shrinkage and selection operator, the strongest associations for CV death/HHF were obtained for NT-proBNP [HR 1.91 per 1-SD in log-transformed biomarker], HF (HR 1.72), and diabetes (HR 1.56). Conclusions Diabetes and HF were independently associated with an increased risk of CV death/HHF in an unselected AF patient population, and NT-proBNP improved risk assessment. These findings suggest that AF patients with diabetes and/or HF should be managed not only for their risk of stroke and systemic embolic events but also for CV death/HHF.

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“…These results indicate a complementary value of dapagliflozin in addition to the established combined therapy for HF and Worsening HF episodes (either unplanned hospitalization or urgent heart failure visit requiring intravenous therapy but not requiring a hospital admission) or CV death, analyzed as time to first event either in the full population or in patients with LVEF \ 60% further evidence for its use in ambulatory patients with HFrEF to improve clinical outcomes [25]. Finally, an exploratory analysis on the effect of dapagliflozin on incident T2D in the cohort without diabetes enrolled in the trial showed that treatment with dapagliflozin reduced the incidence of new diabetes [26] and therefore could be exerting a protective effect in these patients with HF where the risk of developing diabetes is elevated.…”

Section: Mechanism Effectmentioning

confidence: 99%

Benefits of SGLT2i for the Treatment of Heart Failure Irrespective of Diabetes Diagnosis: A State-of-the-Art Review

2022

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Morbidity and mortality associated with heart failure (HF) has remained high despite advances in therapy. Furthermore, HF-associated risk in patients with type 2 diabetes mellitus (T2D) is even higher than in patients without T2D owing to the strong reciprocal relationship between conditions. However, until recently, no therapy to treat patients with diabetes also reduced cardiovascular risks related to HF. Recent clinical studies (DAPA-HF, EMPEROR-Reduced and EMPEROR-Preserved, SOLOIST-WHF trial) and meta-analysis have demonstrated that sodium-glucose cotransporter-2 inhibitors (SGLT2i) are among the first antidiabetic drugs capable of reducing cardiovascular risks related to HF and improving the prognosis of patients with and without diabetes. Their pleiotropic mechanisms of action place them at the intersection of hemodynamic, metabolic, Elı ´as Delgado, Esteban Jo ´dar, Pedro Mezquita-Raya, and O ´scar Moreno-Pe ´rez have equally participated in the development of the manuscript.

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

Cited by 8 publications

References 0 publications

Association between prediabetes and adverse outcomes in heart failure

Association between prediabetes and adverse outcomes in heart failure

Relationship of diabetes, heart failure, and N‐terminal pro‐B‐type natriuretic peptide with cardiovascular outcomes in patients with atrial fibrillation

Benefits of SGLT2i for the Treatment of Heart Failure Irrespective of Diabetes Diagnosis: A State-of-the-Art Review

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