Abstract:Aims Impairment of vascular function contributes to the progression of chronic heart failure (HF) by increasing the afterload. Treatment with selective sodium-glucose cotransporter 2 (SGLT2) inhibitors improves the prognosis of HF, but the precise mechanisms remain unclear. The aim of this study was to analyse the effect of empagliflozin on vascular function in patients with HF.
Methods and resultsIn an investigator initiated, double-blind, randomized, placebo-controlled, parallel-group, clinical study, patien… Show more
“…When we also excluded the other trial performed in the HFrEF population, 28 we observed that SGLT-2 inhibitor compared to control led to a significant decrease in PWV by 0.17 m/s (MD = −0.17, 95% CI −0.31 to −0.04, I 2 = 0%, p = 0.01), with complete elimination of the observed heterogeneity. Of note, this analysis corresponds to the effect of SGLT-2 inhibitors on PWV in subjects with T2DM at background, showing a favorable effect on that cardiovascular risk marker.…”
Section: Resultsmentioning
confidence: 92%
“…We pooled data from six trials in a total of 452 enrolled participants assigned either to SGLT-2 inhibitor or control. [26][27][28][29][30][31] All trials enrolled subjects with T2DM except for two trials performed by Requena-Ibáñez et al, 27 in which none of the participants had a prior diagnosis of T2DM, and by Kolwelter et al, 28 who enrolled subjects with a prior diagnosis of heart failure with reduced ejection fraction (HFrEF), from whom less than one-fourth suffered from T2DM prior to inclusion in the trial. A thorough description of participants' baseline characteristics of interest along with PWV analysis methods is provided in Table 1.…”
Section: Results Of Search and Trial Characteristicsmentioning
Background: Arterial stiffness represents an established cardiovascular risk marker. Sodium-glucose co-transporter-2 (SGLT-2) inhibitors have significant cardio-protective effects. Herein we sought to determine the effect of SGLT-2 inhibitors on pulse wave velocity (PWV). Methods: We searched PubMed, Cochrane Library, and grey literature from inception to 7th February 2022 for randomized controlled trials (RCTs) enrolling adult subjects with or without type 2 diabetes mellitus (T2DM), assigned to a SGLT-2 inhibitor versus control and addressing their effect on PWV. We set as primary efficacy outcome the change in PWV with SGLT-2 inhibitors versus placebo or control. Results: We pooled data from six trials in a total of 452 enrolled participants assigned either to SGLT-2 inhibitor or control. Overall, SGLT-2 inhibitor treatment compared to control resulted in a nonsignificant decrease in PWV. Exclusion of a trial utilizing cardiac magnetic resonance imaging for the assessment of PWV demonstrated that SGLT-2 inhibitors induce a significant reduction in PWV by 0.21 m/s. When we restricted our analysis to RCTs enrolling subjects with T2DM, we observed that SGLT-2 inhibitor compared to control resulted in a significant decrease in PWV by 0.17 m/s. Conclusion: SGLT-2 inhibitors do not decrease PWV in patients with established cardiovascular disease or cardiovascular risk factors. However, we have shown that SGLT-2 inhibitors lead to a slight, but significant decrease in PWV in patients with T2DM. The latter finding is of great value, based on the significant correlation between PWV and micro- and macro-vascular complications of T2DM.
“…When we also excluded the other trial performed in the HFrEF population, 28 we observed that SGLT-2 inhibitor compared to control led to a significant decrease in PWV by 0.17 m/s (MD = −0.17, 95% CI −0.31 to −0.04, I 2 = 0%, p = 0.01), with complete elimination of the observed heterogeneity. Of note, this analysis corresponds to the effect of SGLT-2 inhibitors on PWV in subjects with T2DM at background, showing a favorable effect on that cardiovascular risk marker.…”
Section: Resultsmentioning
confidence: 92%
“…We pooled data from six trials in a total of 452 enrolled participants assigned either to SGLT-2 inhibitor or control. [26][27][28][29][30][31] All trials enrolled subjects with T2DM except for two trials performed by Requena-Ibáñez et al, 27 in which none of the participants had a prior diagnosis of T2DM, and by Kolwelter et al, 28 who enrolled subjects with a prior diagnosis of heart failure with reduced ejection fraction (HFrEF), from whom less than one-fourth suffered from T2DM prior to inclusion in the trial. A thorough description of participants' baseline characteristics of interest along with PWV analysis methods is provided in Table 1.…”
Section: Results Of Search and Trial Characteristicsmentioning
Background: Arterial stiffness represents an established cardiovascular risk marker. Sodium-glucose co-transporter-2 (SGLT-2) inhibitors have significant cardio-protective effects. Herein we sought to determine the effect of SGLT-2 inhibitors on pulse wave velocity (PWV). Methods: We searched PubMed, Cochrane Library, and grey literature from inception to 7th February 2022 for randomized controlled trials (RCTs) enrolling adult subjects with or without type 2 diabetes mellitus (T2DM), assigned to a SGLT-2 inhibitor versus control and addressing their effect on PWV. We set as primary efficacy outcome the change in PWV with SGLT-2 inhibitors versus placebo or control. Results: We pooled data from six trials in a total of 452 enrolled participants assigned either to SGLT-2 inhibitor or control. Overall, SGLT-2 inhibitor treatment compared to control resulted in a nonsignificant decrease in PWV. Exclusion of a trial utilizing cardiac magnetic resonance imaging for the assessment of PWV demonstrated that SGLT-2 inhibitors induce a significant reduction in PWV by 0.21 m/s. When we restricted our analysis to RCTs enrolling subjects with T2DM, we observed that SGLT-2 inhibitor compared to control resulted in a significant decrease in PWV by 0.17 m/s. Conclusion: SGLT-2 inhibitors do not decrease PWV in patients with established cardiovascular disease or cardiovascular risk factors. However, we have shown that SGLT-2 inhibitors lead to a slight, but significant decrease in PWV in patients with T2DM. The latter finding is of great value, based on the significant correlation between PWV and micro- and macro-vascular complications of T2DM.
“…We showed reduced office BP and improved metabolic control, findings well described in our previous studies [ 22 , 35 ]. In a previously published analysis that focused on vascular effects in patients with CHF, we showed a significant decrease in central systolic BP and central pulse pressure under resting conditions as well as under 24-h ambulatory conditions after 1 and 3 months of treatment with empagliflozin [ 17 ]. These effects are mediated by the reduction of the preload through natriuresis and osmotic diuresis as well as of the afterload through reducing the arterial stiffness (indicated by the decrease in central BP and improving vascular function [ 17 , 31 ].…”
Section: Discussionmentioning
confidence: 99%
“…1 ). The results on vascular parameters under 24-h daily conditions as well as under laboratory conditions were already previously published [ 17 ]. Fig.…”
Introduction
Sodium-glucose co-transporter 2 (SGLT2) inhibitors have cardiovascular protective properties in addition to the metabolic effects and represent a cornerstone of treating patients with chronic heart failure (CHF). We hypothesised that empagliflozin reduces tissue sodium content in patients with CHF.
Methods
In a double-blind, randomised (2:1), placebo-controlled, parallel-group, clinical trial, 74 patients with NYHA class II–III CHF and an ejection fraction of 49% or less received empagliflozin 10 mg once daily or placebo for 3 months. In each patient, tissue sodium content of the lower leg was assessed non-invasively by sodium-MRI (23Na-MRI) at baseline, after 1 and 3 months of treatment.
Results
After 1 and 3 months treatment with empagliflozin (n = 48), a significant decrease in skin sodium content was observed (1 month: 22.8 ± 6.1 vs. 21.6 ± 6.0 AU, p = 0.039; 3 months: 22.9 ± 6.1 vs. 21.6 ± 6.1 AU, p = 0.013), while there was no change in muscle sodium and muscle water content. In direct comparison, the change in skin sodium content between baseline and 3 months was − 1.3 ± 3.5 AU in the empagliflozin group versus 0.6 ± 3.5 AU in the placebo group (p for between-group difference = 0.022). No significant difference regarding change in muscle sodium and in muscle water content was observed after 3 months treatment between the two groups.
Conclusion
This trial showed a significant decrease in skin sodium content after 1 and 3 months of treatment with empagliflozin. The decrease in skin sodium content may reflect a decrease in subclinical micro-oedema or/and in non-osmotic bound tissue sodium, both reported to impair left ventricular function.
Trial registration number
NCT03128528 (http://www.clinicaltrials.gov).
Trial registration date
25th April 2017.
“…Vascular metrics such as central systolic blood pressure (cSBP), central pulse pressure (cPP), forward pressure height (FPH), and reflected pressure pulse height (RPH) under basal conditions decreased in the EMPA therapy group (n = 45) after one and three months. The decreased afterload of the left ventricle caused by greater arterial and aortic compliance perhaps led to a better prognosis seen in HF patients taking SGLT2 inhibition [ 21 ].…”
Despite the existence of effective medicines, heart failure continues to be the largest cause of illness and death worldwide. As a prospective family of drugs with potential cardiovascular advantages in non-diabetic patients, sodium-glucose co-transporter 2 inhibitors (SGLT2-I) have recently come to the forefront. In this comprehensive study, we assessed the favorable cardiovascular outcomes of SGLT2-I in three sizable, randomized trials with both diabetic and non-diabetic populations. The results from these studies revealed a substantial reduction in heart failure hospitalizations and cardiovascular and all-cause deaths. To further support our assertion that SGLT2-I has the potential to be a novel addition to the standard treatment plan for heart failure, we also tried to assemble several post hoc and prespecified studies of the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) study. The details of two clinical investigations that supported their use in acute decompensated heart failure were also examined, along with the most plausible mechanism of action generating their cardioprotective effects. Additionally, positive cardiovascular advantages were addressed in chronic heart failure with both preserved and reduced ejection fractions. The role of SGLT2-I in ST-elevation myocardial infarction (STEMI) and hypertrophic cardiomyopathy (HOCM) patients is currently being studied, and this research has the potential to be revolutionary. The purpose of this systematic review is to compile all information that supports the use of this life-saving drug in patients who do not have diabetes so that cardiac care can be improved globally.
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