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 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.

scholarly journals Clinical Characteristics and Outcomes of Patients With Heart Failure With Reduced Ejection Fraction and Chronic Obstructive Pulmonary Disease: Insights From PARADIGM‐HF

2021 ◽  
Vol 10 (4) ◽  
Author(s):  
Solmaz Ehteshami‐Afshar ◽  
Leanne Mooney ◽  
Pooja Dewan ◽  
Akshay S. Desai ◽  
Ninian N. Lang ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Obstructive Pulmonary Disease ◽  
Ejection Fraction ◽  
Pulmonary Disease ◽  
Cardiovascular Death ◽  
Chronic Obstructive ◽  
Heart Failure Hospitalization ◽  
Obstructive Pulmonary Disease ◽  
Reduced Ejection Fraction ◽  
Patients With Heart Failure

Background Chronic obstructive pulmonary disease (COPD) is a common comorbidity in heart failure with reduced ejection fraction, associated with undertreatment and worse outcomes. New treatments for heart failure with reduced ejection fraction may be particularly important in patients with concomitant COPD. Methods and Results We examined outcomes in 8399 patients with heart failure with reduced ejection fraction, according to COPD status, in the PARADIGM‐HF (Prospective Comparison of Angiotensin Receptor Blocker–Neprilysin Inhibitor With Angiotensin‐Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial. Cox regression models were used to compare COPD versus non‐COPD subgroups and the effects of sacubitril/valsartan versus enalapril. Patients with COPD (n=1080, 12.9%) were older than patients without COPD (mean 67 versus 63 years; P <0.001), with similar left ventricular ejection fraction (29.9% versus 29.4%), but higher NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide; median, 1741 pg/mL versus 1591 pg/mL; P=0.01), worse functional class (New York Heart Association III/IV 37% versus 23%; P <0.001) and Kansas City Cardiomyopathy Questionnaire–Clinical Summary Score (73 versus 81; P <0.001), and more congestion and comorbidity. Medical therapy was similar in patients with and without COPD except for beta‐blockade (87% versus 94%; P <0.001) and diuretics (85% versus 80%; P <0.001). After multivariable adjustment, COPD was associated with higher risks of heart failure hospitalization (hazard ratio [HR], 1.32; 95% CI, 1.13–1.54), and the composite of cardiovascular death or heart failure hospitalization (HR, 1.18; 95% CI, 1.05–1.34), but not cardiovascular death (HR, 1.10; 95% CI, 0.94–1.30), or all‐cause mortality (HR, 1.14; 95% CI, 0.99–1.31). COPD was also associated with higher risk of all cardiovascular hospitalization (HR, 1.17; 95% CI, 1.05–1.31) and noncardiovascular hospitalization (HR, 1.45; 95% CI, 1.29–1.64). The benefit of sacubitril/valsartan over enalapril was consistent in patients with and without COPD for all end points. Conclusions In PARADIGM‐HF, COPD was associated with lower use of beta‐blockers and worse health status and was an independent predictor of cardiovascular and noncardiovascular hospitalization. Sacubitril/valsartan was beneficial in this high‐risk subgroup. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01035255.

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 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.

P3542Natriuretic peptides added to clinical parameters predict two-year prognosis of patients with chronic heart with mid-range and reduced ejection fraction

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
J Spinar ◽  
L Spinarova ◽  
M Spinarova ◽  
K Labr ◽  
J Jarkovsky ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Ejection Fraction ◽  
Heart Transplantation ◽  
Natriuretic Peptides ◽  
Prognostic Score ◽  
Clinical Status ◽  
Reduced Ejection Fraction ◽  
Nyha Classification ◽  
Patients With Heart Failure

Abstract Background The guidelines recommend to determine natriuretic peptides, clinical status (NYHA classification) and comorbidities in order to predict the prognosis in patients with heart failure. The aim ofthis registry was to develop a prognostic score in chronic heart failure patients, using clinical status, comorbidities and natriuretic peptides. Methods Consecutive 1088 patients with stable chronic heart failure with reduced ejection fraction (HFrEF) (LVEF<40%) and mid-range EF (HFmrEF) (LVEF 40–49%) were enrolled. Two-year all-cause mortality, heart transplantation and/or LVAD implantation were defined as the primary endpoint (MACE). Results The occurrence of MACE was 14.9% and increased with higher NYHA, 4.9% (NYHA I), 11.4% (NYHA II) and 27.8% (NYHA III-IV) (p<0.001). The occurrence of MACE was 3%, 10% and 15–37% in patients with NT-proBNP levels ≤125pg/ml, 126–1000pg/ml and >1000pg/ml respectively. Discrimination abilities of NYHA and NT-proBNP were (AUC 0.670; p<0.001 and AUC 0.722; p<0.001). The predictive value of the developed clinical model, which took account of older age, advanced heart failure (NYHA III+IV), anaemia, hyponatraemia, hyperuricaemia and taking a higher dose of loop diuretics (>40 mg furosemide daily) (AUC 0.773; p<0.001) was increased by adding the NT-proBNP level (AUC 0.790). Conclusion Natriuretic peptides, clinical status and comorbiditis predict two year prognosis and they can help to a better identification of a high-risk groups of patients with heart failure with reduced and mid range ejection fraction in which more intense treatment should be considered, mainly LVAD implantation or listing to heart transplantation waiting list. Acknowledgement/Funding None

LCZ696, an Angiotensin–neprilysin Inhibitor Versus Enalapril in Heart Failure – Summary of PARADIGM-HF Results

2016 ◽  
Vol 02 (01) ◽  
pp. 14 ◽  
Author(s):  
José Silva Cardoso ◽  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Cardiovascular Death ◽  
Reduced Ejection Fraction ◽  
Neprilysin Inhibitor ◽  
Patients With Heart Failure

This editorial summarises important findings from the PARADIGM-HF study. PARADIGM-HF indicated that the angiotensin receptorneprilysin inhibitor, LCZ696, is superior to enalapril in reducing the risks of cardiovascular death and of hospitalisation for heart failure in patients with heart failure and reduced ejection fraction.

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 Dapagliflozin and Diuretic Use in Patients With Heart Failure and Reduced Ejection Fraction in DAPA-HF

Circulation ◽  
2020 ◽  
Vol 142 (11) ◽  
pp. 1040-1054 ◽  
Author(s):  
Alice M. Jackson ◽  
Pooja Dewan ◽  
Inder S. Anand ◽  
Jan Bělohlávek ◽  
Olof Bengtsson ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Diuretic Therapy ◽  
Cardiovascular Death ◽  
Adverse Outcomes ◽  
Unique Identifier ◽  
Reduced Ejection Fraction ◽  
End Point ◽  
Patients With Heart Failure ◽  
Failure Event

Background: In the DAPA-HF trial (Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure), the sodium-glucose cotransporter 2 inhibitor dapagliflozin reduced the risk of worsening heart failure and death in patients with heart failure and reduced ejection fraction. We examined the efficacy and tolerability of dapagliflozin in relation to background diuretic treatment and change in diuretic therapy after randomization to dapagliflozin or placebo. Methods: We examined the effects of study treatment in the following subgroups: no diuretic and diuretic dose equivalent to furosemide <40, 40, and >40 mg daily at baseline. We examined the primary composite end point of cardiovascular death or a worsening heart failure event and its components, all-cause death and symptoms. Results: Of 4616 analyzable patients, 736 (15.9%) were on no diuretic, 1311 (28.4%) were on <40 mg, 1365 (29.6%) were on 40 mg, and 1204 (26.1%) were taking >40 mg. Compared with placebo, dapagliflozin reduced the risk of the primary end point across each of these subgroups: hazard ratios were 0.57 (95% CI, 0.36–0.92), 0.83 (95% CI, 0.63–1.10), 0.77 (95% CI, 0.60–0.99), and 0.78 (95% CI, 0.63–0.97), respectively ( P for interaction=0.61). The hazard ratio in patients taking any diuretic was 0.78 (95% CI, 0.68–0.90). Improvements in symptoms and treatment toleration were consistent across the diuretic subgroups. Diuretic dose did not change in most patients during follow-up, and mean diuretic dose did not differ between the dapagliflozin and placebo groups after randomization. Conclusions: The efficacy and safety of dapagliflozin were consistent across the diuretic subgroups examined in DAPA-HF. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03036124.

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