scholarly journals Mechanisms and Perspectives of Sodium-Glucose Co-transporter 2 Inhibitors in Heart Failure

2021 ◽  
Vol 8 ◽  
Author(s):  
Qingchun Zeng ◽  
Qing Zhou ◽  
Weitao Liu ◽  
Yutong Wang ◽  
Xingbo Xu ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Large Scale ◽  
Heart Diseases ◽  
Cardiovascular Death ◽  
Serum Glucose ◽  
Clinical Syndrome ◽  
Sglt2 Inhibitors ◽  
Reduced Ejection Fraction ◽  
Beneficial Effects

Heart failure (HF) is a common complication or late-stage manifestation of various heart diseases. Numerous risk factors and underlying causes may contribute to the occurrence and progression of HF. The pathophysiological mechanisms of HF are very complicated. Despite accumulating advances in treatment for HF during recent decades, it remains an intractable clinical syndrome with poor outcomes, significantly reducing the quality of life and expectancy of patients, and imposing a heavy economic burden on society and families. Although initially classified as antidiabetic agents, sodium-glucose co-transporter 2 (SGLT2) inhibitors have demonstrated reduced the prevalence of hospitalization for HF, cardiovascular death, and all-cause death in several large-scale randomized controlled clinical trials. These beneficial effects of SGLT-2 inhibitors can be attributed to multiple hemodynamic, inflammatory and metabolic mechanisms, not only reducing the serum glucose level. SGLT2 inhibitors have been used increasingly in treatment for patients with HF with reduced ejection fraction due to their surprising performance in improving the prognosis. In addition, their roles and mechanisms in patients with HF with preserved ejection fraction or acute HF have also attracted attention. In this review article, we discuss the possible mechanisms and applications of SGLT2 inhibitors in HF.

scholarly journals EMPEROR-Preserved: SGLT2 inhibitors breakthrough in the management of heart failure with preserved ejection fraction

2021 ◽  
Vol 2021 (3) ◽  
Author(s):  
Kerolos Wagdy ◽  
Sherif Nagy
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Complex Disease ◽  
Hospital Admissions ◽  
Sglt2 Inhibitor ◽  
Cardiovascular Death ◽  
Sglt2 Inhibitors ◽  
Preserved Ejection Fraction ◽  
Reduced Ejection Fraction ◽  
Sglt2 Inhibition

Background: Heart failure with preserved ejection fraction (HFpEF) is a complex disease which accounts for more than half of all HF hospital admissions with high prevalence and lack of effective evidence-based management. Sodium-glucose cotransporter 2 (SGLT2) inhibitor is a new antidiabetic drug that recently gained a new role in the management of heart failure with reduced ejection fraction but its role in HFpEF had yet to be studied.Study and results: EMPEROR-Preserved trial set out to evaluate the effects of SGLT2 inhibition with empagliflozin on major heart failure outcomes in patients with HFpEF. The patients were randomized in a 1:1 fashion into two groups; to receive either empagliflozin 10 mg per day (n = 2,997) or placebo (n = 2,991) in addition to usual therapy. Empagliflozin led to a 21% risk reduction of the composite of cardiovascular death or hospitalization for heart failure, which was mainly related to a 29% lower risk of hospitalization for heart failure rather than effect on cardiovascular death empagliflozin. The effects SGLT2 inhibitors were consistent in all patients.

scholarly journals Lessons learned from the DAPA-HF trial concerning the mechanisms of benefit of SGLT2 inhibitors on heart failure events in the context of other large-scale trials nearing completion

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Milton Packer
Keyword(s):  
Heart Failure ◽  
Large Scale ◽  
Cardiovascular Death ◽  
Sglt2 Inhibitors ◽  
Adverse Outcomes ◽  
Lessons Learned ◽  
Reduced Ejection Fraction ◽  
Sodium Glucose Cotransporter ◽  
Patients With Diabetes ◽  
Artery Disease

Abstract Four large-scale trials in type 2 diabetes have shown that sodium-glucose cotransporter 2 (SGLT2) inhibitors prevent the occurrence of serious heart failure events. Additionally, the DAPA-HF trial demonstrated a benefit of dapagliflozin to reduce major adverse outcomes in patients with established heart failure with a reduced ejection fraction. The trial sheds light on potential mechanisms. In DAPA-HF, the benefits of dapagliflozin on heart failure were seen to a similar extent in both patients with or without diabetes, thus undermining the hypothesis that these drugs mitigate glycemia-related cardiotoxicity. The action of SGLT2 inhibitors to promote ketogenesis is also primarily a feature of the action of these drugs in patients with diabetes, raising doubts that enhanced ketogenesis contributes to the benefit on heart failure. Also, dapagliflozin does not have a meaningful effect to decrease circulating natriuretic peptides, and it did not potentiate the actions of diuretics in DAPA-HF; moreover, intensification of diuretics therapy does not reduce cardiovascular death, questioning a benefit of SGLT2 inhibitors that is mediated by an action on renal sodium excretion. Finally, although hematocrit increases with SGLT2 inhibitors might favorably affect patients with coronary artery disease, in DAPA-HF, the benefit of dapagliflozin was similar in patients with or without an ischemic cardiomyopathy; furthermore, increases in hematocrit do not favorably affect the clinical course of patients with heart failure. Therefore, the results of DAPA-HF do not support many currently-held hypotheses about the mechanism of action of SGLT2 inhibitors in heart failure. Ongoing trials are likely to provide further insights.

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 Sodium–Glucose Co-transporter 2 Inhibitors in Heart Failure: Recent Data and Implications for Practice

2020 ◽  
Vol 6 ◽  
Author(s):  
Giuseppe Rosano ◽  
David Quek ◽  
Felipe Martínez
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Ejection Fraction ◽  
Large Scale ◽  
Chronic Phase ◽  
Cardiovascular Death ◽  
Reduced Ejection Fraction ◽  
Patients With Heart Failure ◽  
Sglt2 Inhibition ◽  
Outcome Trial

Heart failure is a shared chronic phase of many cardiac diseases and its prevalence is on the rise globally. Previous large-scale cardiovascular outcomes trials of sodium–glucose co-transporter 2 (SGLT2) inhibitors in patients with type 2 diabetes (T2D) have suggested that these agents may help to prevent primary and secondary hospitalisation due to heart failure and cardiovascular death in these patients. Data from the Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure (DAPA-HF) and Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction (EMPEROR-Reduced) have demonstrated the positive clinical impact of SGLT2 inhibition in patients with heart failure with reduced ejection fraction both with and without T2D. These data have led to the approval of dapagliflozin for the treatment of patients with heart failure with reduced ejection fraction, irrespective of T2D status. This article reviews the latest data reported from the DAPA-HF and EMPEROR-Reduced trials and their clinical implications for the treatment of patients with heart failure.

Abstract 17470: Racial Disparities in Goal Directed Medical Therapy in Patients With Systolic Heart Failure- A Single Center Study

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Ayesha Azmeen ◽  
Naga Vaishnavi Gadela ◽  
Vergara Cunegundo
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Racial Disparities ◽  
Beta Blockers ◽  
Systolic Heart Failure ◽  
The United States ◽  
Clinical Syndrome ◽  
Single Center ◽  
Geographic Variations ◽  
Reduced Ejection Fraction

Introduction: Heart failure(HF) is a clinical syndrome that is widely prevalent affecting approximately 6.5 million people in the United States. It accounts for the ever-rising health care costs in the US due to recurrent hospitalizations. Despite advancements in medical management, the mortality and the rate of hospitalizations continues to be high with geographic variations and racial disparities. Through this descriptive study, we sought to analyze the health disparities among Hispanic, African American (AA) and Caucasian population in a single-center. Methods: We identified a total of 178 patients with HF with reduced ejection fraction from our outpatient clinic by utilizing the ICD-10 codes. Patients with ejection fraction >50% have been excluded. A retrospective chart review of their ethnic background, medications, and number of heart failure exacerbations per year has been performed. Results: 178 patients (mean age 62 years, 35.56% of females) including Hispanics (n=102), AA(n=44), and Caucasians (n=32) were included in the study. Although all patients were started on Beta-blockers, only 76.4% and 37.2% of Hispanics were started on ACEi/ARBs and spironolactone respectively. Similarly, 72.7% and 45.4% of AA were started on ACEi/ARBs and spironolactone respectively. This is in contrast to Caucasians population, where a majority of patients were on started on GDMT; 90% and 75% were started on ACEi/ARBs and spironolactone respectively. This was also reflected by the number of admissions due to HF exacerbations which ranged from 2-4/year for Hispanics and AA populations and 0-1/year for Caucasians. Conclusions: GDMT for HF is known to reduce heart failure exacerbations, mortality and the ever rising cost of the healthcare system. We have observed that despite recommendations to initiate GDMT in all patients with HF with reduced ejection fraction, racial disparities exist. Physicians should be mindful of initiating GDMT in all patients.

scholarly journals SGLT 2 INHIBITORS: NEWER PARADIGMS IN THE TREATMENT OF HEART FAILURE WITH REDUCED EJECTION FRACTION

2021 ◽  
Vol 9 (11) ◽  
pp. 1043-1046
Author(s):  
Shaista Alvi
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Ejection Fraction ◽  
Randomized Controlled Trials ◽  
Large Scale ◽  
Controlled Trials ◽  
Reduced Ejection Fraction ◽  
Randomized Controlled

Heart Failure is a growing concern now a days. Many drugs are available for the treatment of heart failure but still there is increasing prevalence of heart failure. SGLT 2 inhibitors were initially developed for diabetes mellitus but they are found to be effective for Heart Failure with reduced ejection also. Many large scale randomized controlled trials also confirmed this and now they are recommended in the treatment of heart failure with reduced ejection fraction.

Abstract 16392: The Effect of Dapagliflozin on Anemia in Patients With Heart Failure and Reduced Ejection Fraction: An Analysis of DAPA-HF

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Kieran Docherty ◽  
Silvio E Inzucchi ◽  
Lars Kober ◽  
Mikhail Kosiborod ◽  
Anna Maria Langkilde ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Primary Outcome ◽  
Placebo Treatment ◽  
Cardiovascular Death ◽  
Treatment Allocation ◽  
Reduced Ejection Fraction ◽  
Improved Outcomes ◽  
Patients With Heart Failure

Background: Anemia is common and associated with worse outcomes in patients with heart failure and reduced ejection fraction (HFrEF). We examined: 1) whether dapagliflozin corrected anemia in these patients, and 2) the effect of dapagliflozin on outcomes, in patients with or without anemia, in DAPA-HF. Methods: Anemia was defined as baseline hematocrit <39% in men and <36% in women (WHO). Correction of anemia was defined as two consecutive hematocrit measurements above these thresholds at any time during follow-up (follow-up visits: 2 weeks, 2 and 4 months and 4-monthly thereafter). The primary outcome was a composite of worsening HF (hospitalization or urgent visit requiring intravenous therapy) or cardiovascular death. Findings: Of the 4744 patients randomized in DAPA-HF, 4691 had a baseline hematocrit and 1032 were anemic (22.0%). Anemia was corrected in 62% of patients in the dapagliflozin group, compared with 41% of patients in the placebo group (odds ratio 2.37 [95% CI 1.84-3.04]; p<0.001). The effect of dapagliflozin on the primary outcome was consistent in anemic and non-anemic patients (HR 0.68 [95% CI 0.52-0.88] versus 0.76 [0.65-0.89]; P-interaction=0.44) [Figure]. A consistent benefit was also observed for the secondary outcomes, irrespective of anemia status t baseline. Patients with resolution of anemia had better outcomes than those with persisting anemia: rate of primary outcome 9.9 per 100 patient-years (95% CI 8.0-12.4) in those with resolution versus 24.1 per 100 patient-years (20.4-28.3) in those without anemia resolution. Interpretation: Anemia was common in patients in DAPA-HF and associated with worse outcomes. Resolution of anemia was associated with better outcomes than persistence of anemia, regardless of treatment allocation. Although dapagliflozin corrected anemia more often than placebo, treatment with dapagliflozin improved outcomes, irrespective of anemia status.

Chronic heart failure diagnosis: HFpEF

ESC CardioMed ◽  
2018 ◽  
pp. 1762-1768
Author(s):  
Daniel N. Silverman ◽  
Sanjiv J. Shah
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Cardiopulmonary Exercise Testing ◽  
Clinical History ◽  
Right Heart Catheterization ◽  
Clinical Syndrome ◽  
Exercise Intolerance ◽  
Heart Catheterization ◽  
Reduced Ejection Fraction ◽  
Treatment Measures

Heart failure (HF) with preserved ejection fraction (HFpEF) is a very common clinical syndrome that is often misdiagnosed or overlooked due to diagnostic challenges with the lack of a specific imaging test or biomarker to make a conclusive diagnosis. Unlike HF with reduced ejection fraction, neither a reduced ejection fraction nor a dilated left ventricle is available to easily make the diagnosis of HFpEF. Furthermore, while echocardiographic evidence of diastolic dysfunction is common in patients with HFpEF, it is not a universal phenomenon. Even natriuretic peptides, which are generally thought to have good negative predictive value for the diagnosis of HF, are frequently not elevated in HFpEF patients. Finally, the cardinal symptoms of HFpEF such as dyspnoea and exercise intolerance are non-specific and may be due to many of the co-morbidities present in patients in whom the HFpEF diagnosis is entertained. This chapter presents a step-wise approach utilizing a careful clinical history, physical examination, natriuretic peptide testing, and echocardiography, which can reliably provide appropriate information to rule in or rule out the HFpEF diagnosis in the majority of patients. If there is still a question about the diagnosis, or if initial general treatment measures for the HF syndrome do not result in clinical improvement, additional testing such as right heart catheterization or cardiopulmonary exercise testing can be performed to further confirm the diagnosis. With a systematic approach to the patient with dyspnoea, the accurate diagnosis of HFpEF can be made reliably so that these high-risk patients can be appropriately treated.

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