Effect of empagliflozin on ventricular arrhythmias in patients with type 2 diabetes treated with an implantable cardioverter-defibrillator: the EMPA-ICD trial.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of hospitalization for heart failure and cardiovascular death with type 2 diabetes; however, their effect on arrhythmias is unclear. The purpose of this study was to investigate the effects of empagliflozin on ventricular arrhythmias in patients with type 2 diabetes. A total of 150 patients with type 2 diabetes who were treated with an implantable cardioverter-defibrillator or cardiac resynchronization therapy defibrillator (ICD/CRT-D) were randomized to once-daily empagliflozin or placebo for 24 weeks. The primary endpoint was the change in the number of ventricular arrhythmias from the 24 weeks before to the 24 weeks during treatment. Secondary endpoints included the change in the number of appropriate device discharges and other values. In the empagliflozin group, the number of ventricular arrhythmias recorded by ICD/CRT-D decreased by 1.69 during treatment compared to before treatment, while in the placebo group, the number increased by 1.79. The coefficient for the between-group difference was - 1.07 (95% confidence interval [CI] - 1.29 to - 0.86; P < 0.001). The change in the number of appropriate device discharges during and before treatment was 0.06 in the empagliflozin group and 0.27 in the placebo group, with no significant difference between the groups (P = 0.204). Empagliflozin was associated with an increase in blood ketones and hematocrit and a decrease in blood brain natriuretic peptide and body weight. In patients with type 2 diabetes treated with ICD/CRT-D, empagliflozin reduces the number of ventricular arrhythmias compared with placebo. Trial registration jRCTs031180120.

Fujiki S ，Iijima K ，Nakagawa Y ，Takahashi K ，Okabe M ，Kusano K ，Owada S ，Kondo Y ，Tsujita K ，Shimizu W ，Tomita H ，Watanabe M ，Shoda M ，Watanabe M ，Tokano T ，Murohara T ，Kaneshiro T ，Kato T ，Hayashi H ，Maemura K ，Niwano S ，Umemoto T ，Yoshida H ，Ota K ，Tanaka T ，Kitamura N ，Node K ，Minamino T ，EMPA ICD investigators ... -  《Cardiovascular Diabetology》

The effects of empagliflozin on ventricular arrhythmias in heart failure patients with an implantable cardioverter-defibrillator: a double-blind randomized controlled trial.

Sodium-glucose transporter 2 (SGLT2) inhibitors such as empagliflozin are one of the main treatments for type 2 diabetes mellitus (DM2) and heart failure (HF). They have also demonstrated anti-arrhythmic effects in some preclinical and clinical studies. The purpose of this study was to assess the effects of empagliflozin on ventricular arrhythmias in HF patients with an implantable cardioverter-defibrillator (ICD). In a prospective double-blinded, randomized controlled trial of Iran County, Mashhad (72 patients 1:1), we compared the frequency and proportion of ventricular arrhythmias and ICD therapies during the 24 weeks to the prior 24 weeks. Results revealed that empagliflozin significantly reduced the frequency and proportion of ventricular tachycardia (VT)/fibrillation (VF) episodes (P = 0.019 and 0.039, respectively). Moreover, it tended to reduce the frequency and proportion of ICD therapies, including anti-tachycardia pacing (ATP) and shock. Subgroup analysis of patients with or without any antiarrhythmic drugs (digoxin, mexiletine, amiodarone, or sotalol) revealed that only patients who were previously on the antiarrhythmic drugs benefit from empagliflozin antiarrhythmic effects. In conclusion, empagliflozin exhibits anti-arrhythmic effects in HF patients with an ICD. Larger and long-term clinical studies are still needed to investigate and confirm all positive effects of SGLT2 inhibitors in this regard. Trial registration number: IRCT20120520009801N7 (Approval date: June 11, 2022).

Abedi F ，Mohammadpour AH ，Ghavami V ，Heidari-Bakavoli A ，Jomezadeh V ，Tayyebi M ... -  《-》

Empagliflozin's role in reducing ventricular repolarization heterogeneity: insights into cardiovascular mortality decline from the EMPATHY-HEART trial.

The incidence of myocardial infarction (MI) and sudden cardiac death (SCD) is significantly higher in individuals with Type 2 Diabetes Mellitus (T2DM) than in the general population. Strategies for the prevention of fatal arrhythmias are often insufficient, highlighting the need for additional non-invasive diagnostic tools. The T-wave heterogeneity (TWH) index measures variations in ventricular repolarization and has emerged as a promising predictor for severe ventricular arrhythmias. Although the EMPA-REG trial reported reduced cardiovascular mortality with empagliflozin, the underlying mechanisms remain unclear. This study investigates the potential of empagliflozin in mitigating cardiac electrical instability in patients with T2DM and coronary heart disease (CHD) by examining changes in TWH. Participants were adult outpatients with T2DM and CHD who exhibited TWH > 80 µV at baseline. They received a 25 mg daily dose of empagliflozin and were evaluated clinically including electrocardiogram (ECG) measurements at baseline and after 4 weeks. TWH was computed from leads V4, V5, and V6 using a validated technique. The primary study outcome was a significant (p < 0.05) change in TWH following empagliflozin administration. An initial review of 6,000 medical records pinpointed 800 patients for TWH evaluation. Of these, 412 exhibited TWH above 80 µV, with 97 completing clinical assessments and 90 meeting the criteria for high cardiovascular risk enrollment. Empagliflozin adherence exceeded 80%, resulting in notable reductions in blood pressure without affecting heart rate. Side effects were generally mild, with 13.3% experiencing Level 1 hypoglycemia, alongside infrequent urinary and genital infections. The treatment consistently reduced mean TWH from 116 to 103 µV (p = 0.01). The EMPATHY-HEART trial preliminarily suggests that empagliflozin decreases heterogeneity in ventricular repolarization among patients with T2DM and CHD. This reduction in TWH may provide insight into the mechanism behind the decreased cardiovascular mortality observed in previous trials, potentially offering a therapeutic pathway to mitigate the risk of severe arrhythmias in this population. NCT: 04117763.

Lauretti C ，Antonio GL ，Fernandes AE ，Stocco FG ，Girardi ACC ，Verrier RL ，Caramelli B ... -  《-》

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》

Effect of empagliflozin on weight in patients with prediabetes and diabetes.

The impact of blood glucose-lowering medications on weight has always been a topic of interest in the treatment of diabetic patients. This study investigates the effect of empagliflozin on weight in patients with prediabetes and type 2 diabetes. This quasi-experimental study was performed on patients with prediabetes or type 2 diabetes with an HbA1c level up to 1% higher than the treatment target, and not using other blood glucose-lowering medications. Patients received 10 milligrams of Empagliflozin once daily for three months, and weight, BMI, waist circumference, and blood pressure were evaluated monthly. Forty-three patients (21 women and 22 men) enrolled. The average weight of patients decreased by 2.96 ± 1.96 kg (3.8%) (P < 0.001). BMI decreased by -1.10 ± 0.71 Kg/m2 (3.72%) (P < 0.001). The waist circumference of patients decreased by -3.23 ± 3.69 centimeters (P < 0.001). FPG decreased from 114.86 to 109.48 mg/dL (P < 0.001), and HbA1c decreased from 6.52% to 6.38% (P < 0.001). The weight change was more significant in men than women (-3.59 ± 1.74 vs. -2.30. ± 1.99), (P = 0.029). Weight reduction was greater in patients with GFR higher than 90 compared to GFR lower than 90 (-3.34. ± 2.00 vs. -2.16 ± 1.67) (P = 0.063). Also, no significant difference was observed in the weight, BMI, and waist circumference changes between different BMI groups (less than 25, 25 to 30, 30 to 35, and higher than 35). The trend of weight and BMI changes during the three-month empagliflozin treatment period was significant (P < 0.001) and didn't reach a plateau level after three months. The change in waist circumference was also significant, reaching a plateau level after one month (P < 0.001). There was no significant change in blood pressure. In conclusion the weight, BMI, and waist circumference of patients decreased following the administration of empagliflozin. Weight reduction was more pronounced in males than females and in patients with a GFR above 90 than those with a GFR below 90. Trial registration: This study was approved by the Research Deputy of Kerman University of Medical Sciences with tracking number 401,000,516, IRCT code: IRCT20090317001774N10, and ethical code: IR.KMU.AH.REC.1402.065 was approved by Research Ethics Committee of Afzalipour Hospital- Kerman University of Medical Sciences.

Sanjari M ，Hadavizadeh M ，Sadeghi N ，Naghibzadeh-Tahami A ... -  《-》