Dapagliflozin in Heart Failure: A Comprehensive Meta-analysis on Functional Capacity, Symptoms, and Safety Outcomes.

To evaluate the comparative effects of dapagliflozin versus placebo in patients with heart failure (HF), focusing on functional capacity, symptoms, and safety outcomes. Despite advancements in heart failure (HF) therapy, HF is still a significant cause of recurrent hospitalization and death worldwide. Dapagliflozin has demonstrated potential in lowering hospitalizations and mortality associated with heart failure; however, its impact on functional capacity, particularly the 6-min walk distance (6MWD), and the comprehensive assessment of safety outcomes in diverse HF populations, including those with preserved or reduced ejection fraction (HFpEF and HFrEF, respectively), requires further investigation. PubMed, Web of Science, Cochrane Library, and Scopus databases were comprehensively searched to identify randomized controlled trials (RCTs) investigating the efficacy of dapagliflozin in comparison with control interventions for heart failure. The primary outcome was a change in the 6MWD, KCCQ score, and safety measures included hospitalization, all-cause mortality, and adverse events. In our meta-analysis of ten studies involving 12,695 patients with heart failure, dapagliflozin showed significantly improved Kansas City Cardiomyopathy Questionnaire (KCCQ) scores [risk ratio (RR) of 2.75, 95% confidence interval (CI) (1.95-3.569), p < 0.00001] and no significant differences in 6-min walk distance [6MWD; RR of 3.59, 95% CI (- 1.44 to 8.63), p = 0.16]. Dapagliflozin demonstrated a notable reduction in hospitalization for heart failure [RR of 0.76, 95% CI (0.68-0.84), p < 0.00001], significant overall reduction on the effect of any cause mortality [RR of 0.90, 95% CI (0.83-0.99), p = 0.03). There was, however, no significant effect on adverse events [RR of 0.96, 95% CI (0.98-1.03), p = 0.39). Our meta-analysis of ten trials concluded that dapagliflozin significantly improved KCCQ scores in both HFrEF and HFpEF. The improvement in 6MWD was not statistically significant but trended toward dapagliflozin. Dapagliflozin also showed a mortality benefit in patients with reduced ejection fraction; however, in patients with preserved ejection fraction, the result was not statistically significant. There was also a statistically significant reduction in heart failure hospitalizations across all classes.

Addo B ，Agyeman W ，Ibrahim S ，Berchie P ... -  《-》

Long-term surrogate cardiovascular outcomes of SGLT2 inhibitor empagliflozin in chronic heart failure: a systematic review and meta-analysis.

The sodium‒glucose cotransporter-2 (SGLT2) inhibitor empagliflozin (EMPA) has been demonstrated to reduce the risk of cardiovascular mortality or hospitalization for heart failure (HF) in patients. Nevertheless, data concerning the long-term cardiovascular effects in clinically important subgroups are scarce. A prespecified meta-analysis of randomized controlled trials (RCTs) was conducted to assess the long-term effects of EMPA on cardiovascular outcomes in HF patients, regardless of HF type and glycemic status. The assessment included parameters related to left ventricular (LV) remodeling, including the LV volume, the LV mass index (LVMI), the ejection fraction, the systolic blood pressure, and biomarkers. Moreover, the effects of the treatment on exercise capacity and quality of life (QoL) were analyzed. Furthermore, these cardiovascular parameters were evaluated in prespecified subgroups of HF patients, including type of HF, type 2 diabetes status, and duration of therapy. The quantitative meta-analysis was synthesized and analyzed via the statistical software Stata 17.0. The meta-analysis revealed that EMPA administration significantly contributed to a reduction in systolic blood pressure (SBP) (MD = 4.93 mmHg, 95% CI=[-9.67, -0.19]; P < 0.0001) and left ventricular end-diastolic volume (LVEDV) (MD=-18.03 mL, 95% CI=[-25.4, -10.67], P < 0.0001). Furthermore, left ventricular end-systolic volume (LVESV) (MD=-16.09 mL, 95% CI=[-26.94, -5.25]; P < 0.0001) and N-terminal pro-B-type NP (NT-proBNP) (SMD=-0.54, 95% CI=[-0.94, -0.13]; P = 0.01) significantly decreased. These decreases were accompanied by improvements in the 6-minute walk distance (6MWD, SMD = 0.78, 95% CI=[-0.22, -1.79], P = 0.13) and KCCQ score (MD = 1.98, 0.97-2.99; P < 0.0001). The results of the subgroup analysis indicated that EMPA administration was associated with more pronounced benefits in terms of cardiac remodeling, function and exercise capacity for specific populations, including (1) HF with a reduced ejection fraction (HFrEF); (2) the absence of diabetes; and (3) treatment for no less than 6 months. Additionally, EMPA may lead to an increased risk of cardiovascular adverse events (AEs) but is less effective for improving the QoL in HF patients with preserved EF (HFpEF) populations.

Yan Q ，Chen X ，Yu C ，Yin Y ... -  《BMC Cardiovascular Disorders》

The effects of Dapagliflozin in a real-world population of HFrEF patients with different hemodynamic profiles: worse is better.

Sodium-Glucose Cotransporter-2 inhibitors (SGLT2i) represent a deep revolution of the therapeutic approach to heart failure (HF), preventing its insurgence but also improving the management of the disease and slowing its natural progression. To date, few studies have explored the effectiveness of SGLT2i and, in particular, Dapagliflozin in a real-world population. Therefore, in this observational prospective study, we evaluated Dapagliflozin's effectiveness in a real-world HF population categorized in the different hemodynamic profiles. From January 2022 to June 2023, we enrolled 240 patients with chronic HF and reduced ejection fraction (HFrEF) on optimal medical therapy, according to 2021 ESC guidelines, that added treatment with Dapagliflozin from the HF Clinics of 6 Italian University Hospitals. Clinical, biochemical, and echocardiographic parameters were collected before and after 6 months of Dapagliflozin introduction. Moreover, the HFrEF population was classified according to hemodynamic profiles (A: SV ≥ 35 ml/m2; E/e' < 15; B: SV ≥ 35 ml/m2; E/e' ≥ 15; C: SV < 35 ml/m2; E/e' < 15; D: SV < 35 ml/m2; E/e' ≥ 15). Then, we compared the Dapagliflozin population with two retrospective HF cohorts, hereinafter referred to as Guide Line 2012 (GL 2012) group and Guide Line 2016 (GL 2016) group, in accordance with the HF ESC guidelines in force at the time of patients enrolment. Precisely, we evaluated the changes to baseline in clinical, functional, biochemical, and echocardiographic parameters and compared them to the GL 2012 and GL 2016 groups. Dapagliflozin population (67.18 ± 11.11 years) showed a significant improvement in the echocardiographic and functional parameters (left ventricular ejection fraction [LVEF], LV end-diastolic volume [LVEDV], LVEDV index, stroke volume index [SVi], left atrium volume index [LAVi], filling pressure [E/e' ratio], tricuspid annular plane systolic excursion [TAPSE], tricuspid annular S' velocity [RVs'], fractional area change [FAC], inferior vena cava [IVC diameter], pulmonary artery systolic pressure [sPAP], NYHA class, and quality of life) compared to baseline. In particular, TAPSE and right ventricle diameter (RVD1) ameliorate in congestive profiles (B and D); accordingly, the furosemide dose significantly decreased in these profiles. Comparing the three populations, the analysis of echocardiographic parameters (baseline vs follow-up) highlighted a significant decrease of sPAP in the Dapagliflozin population (p < 0.05), while no changes were recorded in the GL 2012 and GL 2016 population. Moreover, at the baseline evaluation, the GL 2012 and 2016 groups needed a higher significant dose of furosemide compared to Dapagliflozin group. Finally, Dapagliflozin patients had significantly fewer rehospitalizations (1.25%) compared with the other two groups (GL 2012 18.89%, p 0.0097; GL 2016 15.32%, p 0.0497). We demonstrate that Dapagliflozin is rapidly effective in an HFrEF real-world population; furthermore, the more significant effect is recorded in HFrEF patients with a congestive profile (B and D), supporting the introduction of Dapagliflozin in patients with a congestive profile and a worse prognosis. In conclusion, our data suggest evaluating the patient's hemodynamic state beyond LVEF in HFrEF.

Loria F ，Mone P ，Rispoli A ，Di Fonzo R ，Masarone D ，Mancusi C ，Correale M ，Vitullo A ，Granatiero M ，Mazzeo P ，Mercurio V ，Fiore F ，Di Sarro E ，Falco L ，Izzo C ，Campanile A ，Virtuoso N ，Stabile E ，Bonanno S ，Dattilo G ，Tocchetti CG ，Santulli G ，Vecchione C ，Ciccarelli M ，Visco V ... -  《Cardiovascular Diabetology》

Comparative cardiovascular benefits of individual SGLT2 inhibitors in type 2 diabetes and heart failure: a systematic review and network meta-analysis of randomized controlled trials.

Kongmalai T ，Hadnorntun P ，Leelahavarong P ，Kongmalai P ，Srinonprasert V ，Chirakarnjanakorn S ，Chaikledkaew U ，McKay G ，Attia J ，Thakkinstian A ... -  《Frontiers in Endocrinology》

Dapagliflozin Effects on Cardiac Deformation in Heart Failure and Secondary Clinical Outcome.

Sodium-glucose cotransporter 2 inhibitors were shown to reduce morbidity and mortality in patients with heart failure. This study aims to assess potential effects of dapagliflozin in nondiabetic patients with heart failure with reduced ejection fraction (HFrEF) and heart failure with mildly reduced ejection fraction (HFmrEF) on cardiac function assessed by speckle tracking echocardiography (STE). This randomized, prospective, single-center, open-label trial compared consecutive nondiabetic outpatients with HFrEF or HFmrEF receiving dapagliflozin with patients treated with optimal medical therapy (OMT) except sodium-glucose cotransporter type 2 inhibitors. Primary endpoint was the presence of a significant modification of left ventricular global longitudinal strain, diastolic function (as peak atrial longitudinal strain) and right ventricular function by STE from baseline to 6 months. Cardiovascular events and parameters of congestion were assessed as safety-exploratory endpoints. Overall, 88 patients (38% HFmrEF) were enrolled and randomized to start dapagliflozin on top of OMT (n = 44) or to continue with OMT (n = 44). All STE values improved in the dapagliflozin group after 6 months, whereas there was a nonsignificant improvement in OMT group. Moreover, when comparing the modification of STE parameters at follow-up in patients with HFrEF and HFmrEF, only the main treatment effect resulted statistically significant in both groups (P < 0.0001), indicating a significant difference between dapagliflozin and OMT. This study provided randomized data on the beneficial effect of dapagliflozin in nondiabetic patients with HFrEF and HFmrEF in terms of myocardial performance measured by the most sensitive echocardiographic technique, ie, STE. This suggests its usefulness for left ventricular reverse remodeling and better quality of life in patients with HFrEF and HFmrEF. (Effects of Dapagliflozin on cardiac deformation and clinical outcomes in heart failure with reduced and mildly reduced ejection fraction [DAPA ECHO trial]; EudraCT number: 2021-005394-66).

Pastore MC ，Stefanini A ，Mandoli GE ，Piu P ，Diviggiano EE ，Iuliano MA ，Carli L ，Marchese A ，Martini L ，Pecere A ，Cavigli L ，Giacomin E ，Pagliaro A ，Righini FM ，Sorini Dini C ，Soliman Aboumarie H ，Focardi M ，D'Ascenzi F ，Valente S ，Cameli M ... -  《-》