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Meta-Analysis Assessing the Impact of Major Co-Morbidities, Gender, and Race on Cardiovascular Efficacy of Sodium-Glucose Co-Transporter-2 Inhibitors Among Patients With Heart Failure With Preserved or Reduced Ejection Fraction.
Patoulias, D, Papadopoulos, C, Imprialos, K, Stavropoulos, K, Doumas, M
The American journal of cardiology. 2022;:201-205
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Meta-Analysis Addressing the Effect of Sodium-Glucose Cotransporter 2 Inhibitors on Flow-Mediated Dilation in Patients With Type 2 Diabetes Mellitus.
Patoulias, D, Papadopoulos, C, Kassimis, G, Vassilikos, V, Karagiannis, A, Doumas, M
The American journal of cardiology. 2022;:133-135
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Association of Sodium-Glucose Cotransporter 2 Inhibitors With Cardiovascular Outcomes in Patients With Type 2 Diabetes and Other Risk Factors for Cardiovascular Disease: A Meta-analysis.
Bhattarai, M, Salih, M, Regmi, M, Al-Akchar, M, Deshpande, R, Niaz, Z, Kulkarni, A, Siddique, M, Hegde, S
JAMA network open. 2022;(1):e2142078
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Abstract
IMPORTANCE The cardiovascular outcome in selected populations when sodium-glucose cotransporter 2 inhibitors (SGLT2-Is) are emerging as standard therapy is not clearly understood. It is important to learn the magnitude of cardiovascular benefit using SGLT2-Is across the select subgroups that include both sexes and multiple age and racial and ethnic groups. OBJECTIVES To evaluate the association between use of SGLT2-Is and cardiovascular benefits in a prespecified group in a larger sample size using data obtained from randomized clinical trials. DATA SOURCES Search of electronic databases PubMed, Google Scholar, Web of Science, and Cochrane from inception to January 10, 2021, with additional studies identified through conference papers and meeting presentations, ClinicalTrials.gov, and reference lists of published studies. STUDY SELECTION Placebo-controlled randomized clinical trials in which participants had atherosclerotic cardiovascular disease (ASCVD) or risk factors for ASCVD, diabetes, or heart failure and which reported the primary outcome were included in this study. Multicenter observational and nonobservational studies and those with different outcomes of interest were excluded. DATA EXTRACTION AND SYNTHESIS Medical Subject Heading search terms included SGLT2-I and multiple cardiovascular outcomes in different combinations. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. The analysis of all outcomes was performed using a Mantel-Haenszel equation and the random-effects model. MAIN OUTCOMES AND MEASURES Six efficacy outcomes of SGLT2-I use (cardiovascular death and hospitalization for heart failure [HHF] as the primary outcome and major adverse cardiovascular event, HHF, cardiovascular death, acute myocardial infarction, and all-cause mortality as secondary outcomes), were evaluated. Subgroup analysis was performed for the primary outcome of cardiovascular death or HHF. Odds ratios (ORs) and 95% CIs were used to compare 2 interventions. RESULTS Ten studies with 71 553 participants were included, among whom 39 053 received SGLT2-Is; among studies that reported these data, 28 809 were men and 15 655 were women (mean age, 65.2 [range, 61.9-70.0] years). Race and ethnicity were defined in the original trials and were categorized as Asian, Black, or other (6900 participants) and White (26 646 participants) for the purposes of this analysis (the category "other" was not specified consistently). In terms of age, 16 793 were younger than 65 years and 17 087 were 65 years or older. At a mean follow-up 2.3 (range, 0.8-4.2) years, the SGLT2-I group favored reduction in primary outcome (3165 of 39 053 [8.10%] vs 3756 of 32 500 [11.56%]; OR, 0.67 [95% CI, 0.55-0.80]; P < .001). No difference was noted in the rate of acute myocardial infarction compared with the placebo group (1256 of 26 931 [4.66%] vs 958 of 20 373 [4.70%]; OR, 0.95 [95% CI, 0.87-1.03]; P = .22). Subgroup analysis favored SGLT2-I use for the primary outcome in both sexes, age groups, and racial and ethnic groups. CONCLUSIONS AND RELEVANCE This meta-analysis supports that SGLT2-Is have emerged as an effective class of drugs for improving cardiovascular morbidity and mortality in selected patients. Sodium-glucose cotransporter 2 inhibitors were not associated with reduced risk of acute myocardial infarction. Future long-term prospective studies are warranted to understand the long-term cardiovascular benefits.
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Do background ischemic heart disease and baseline left ventricular ejection fraction affect cardiovascular efficacy of SGLT-2 inhibitors in heart failure with reduced ejection fraction?
Patoulias, D, Papadopoulos, C, Kassimis, G, Doumas, M
Journal of cardiovascular medicine (Hagerstown, Md.). 2022;(1):e30-e32
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Effects of SGLT2 inhibitors on cardiovascular outcomes in patients with stage 3/4 CKD: A meta-analysis.
Li, N, Zhou, G, Zheng, Y, Lv, D, Zhu, X, Wei, P, Zheng, M, Liu, S, Zhou, E, Sun, W, et al
PloS one. 2022;(1):e0261986
Abstract
INTRODUCTION After stage 3 CKD, the risk of adverse cardiovascular events increased significantly. Therefore, we performed a meta-analysis to investigate the cardiovascular protective effect of SGLT2 inhibitors in patients with stage 3/4 CKD with different baseline kidney function or underlying diseases. METHOD To identify eligible trials, we systematically searched the Embase, PubMed, Web of Science, and Cochrane library databases from inception to April 15, 2021. The primary cardiovascular outcome was defined as a combination of cardiovascular mortality and hospitalization due to heart failure. Baseline kidney functions (stage 3a CKD: eGFR45-59mL/min per 1.73m2, stage 3b CKD: eGFR30-44mL/min per 1.73m2, stage 4 CKD: eGFR<30mL/min per 1.73m2) and underlying diseases (Type 2 diabetes, heart failure (Preserved ejection fraction or reduced ejection fraction), atherosclerotic cardiovascular disease) were used to stratify efficacy and safety outcomes. The results were subjected to a sensitivity analysis to ensure that they were reliable. RESULTS In the present study, a total of eleven trials were included that involved a total of 27,823 patients with stage 3/4 CKD. The treatment and control groups contained 14,451 and 13,372 patients, respectively. In individuals with stage 3/4 CKD, SGLT2 inhibitors reduced the risk of primary cardiovascular outcomes by 26% (HR 0.74, [95% CI 0.69-0.80], I2 = 0.00%), by 30% in patients with stage 3a CKD (HR 0.70, [95% CI 0.59-0.84], I2 = 18.70%), by 23% in patients with stage 3b CKD (HR 0.77, [95% CI 0.66-0.90], I2 = 2.12%), and by 29% in patients with stage 4 CKD (HR 0.71, [95% CI 0.53-0.96], I2 = 0.00%). The risk of primary outcomes was reduced by 29% (HR 0.71, [95% CI 0.63-0.80], I2 = 0.00%) in patients with type 2 diabetes, by 28% (HR 0.72, [95% CI 0.56-0.93], I2 = 37.23%) in patients with heart failure with preserved ejection fraction, by 21% (HR 0.79, [95% CI 0.70-0.89], I2 = 0.00%) in patients with heart failure with reduced ejection fraction, and by 25% (HR 0.75, [95% CI 0.64-0.88], I2 = 0.00%) in patients with atherosclerotic cardiovascular disease. CONCLUSIONS For stage 3/4 CKD, SGLT2 inhibitors significantly decreased the risk of primary cardiovascular outcomes, and these benefits were consistent throughout the spectrum of different kidney functions, even in stage 4 CKD. There was no evidence of increased adverse outcomes across different baseline clinical complications, such as type 2 diabetes, heart failure, or atherosclerotic cardiovascular disease.
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Association of SGLT2 inhibitors with arrhythmias and sudden cardiac death in patients with type 2 diabetes or heart failure: A meta-analysis of 34 randomized controlled trials.
Fernandes, GC, Fernandes, A, Cardoso, R, Penalver, J, Knijnik, L, Mitrani, RD, Myerburg, RJ, Goldberger, JJ
Heart rhythm. 2021;(7):1098-1105
Abstract
BACKGROUND Sodium-glucose cotransporter 2 inhibitors (SGLT2is) reduce hospitalizations and death from heart failure (HF), but their effect on arrhythmia expression has been poorly investigated. OBJECTIVE The purpose of this study was to evaluate the association of SGLT2is with arrhythmias in patients with type 2 diabetes mellitus (T2DM) or HF. METHODS We searched PubMed and ClinicalTrials.gov. Two independent investigators identified randomized double-blind trials that compared SGLT2is with placebo or active control for adults with T2DM or HF. Primary outcomes were incident atrial arrhythmias, ventricular arrhythmias (VAs), and sudden cardiac death (SCD). RESULTS We included 34 randomized (25 placebo-controlled and 9 active-controlled) trials with 63,166 patients (35,883 SGLT2is vs 27,273 control: mean age 53-67 years; 63% male). Medications included canagliflozin, dapagliflozin, empagliflozin, or ertugliflozin. Except for 1 study of HF, all patients had T2DM. Follow-up ranged from 24 weeks to 5.7 years. The cumulative incidence of events was low: 3.6, 1.4, and 2.5 per 1000 patient-years for atrial arrhythmias, VAs and SCD, respectively. SGLT2i therapy was associated with a significant reduction in the risk of incident atrial arrhythmias (odds ratio 0.81; 95% confidence interval 0.69-0.95; P = .008) and the "SCD" component of the SCD outcome (odds ratio 0.72; 95% confidence interval 0.54-0.97; P = .03) compared with control. There was no significant difference in incident VA or the "cardiac arrest" SCD component between groups. CONCLUSION SGLT2is are associated with significantly reduced risks of incident atrial arrhythmias and SCD in patients with T2DM. Prospective trials are warranted to confirm the antiarrhythmic effect of SGLT2is and whether this is a class or drug-specific effect.
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Regional variation of effects of new antidiabetic medications in cardiovascular outcome trials.
Cotter, G, Davison, BA, Edwards, C, Senger, S, Teerlink, JR, Zannad, F, Nielsen, OW, Metra, M, Mebazaa, A, Chioncel, O, et al
American heart journal. 2021;:73-80
Abstract
BACKGROUND In international trials, glucagon-like protein-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2Is) were effective in improving cardiovascular (CV) outcomes. METHODS We assessed the effect of GLP-1RAs and SGLT2Is treatment effect on CV endpoints by geographical region in multiple international trials using random effects weighted least squares meta-regressions. RESULTS The estimated effects of both SGLT2Is and GLP-1RAs on major adverse CV events (MACE) in North America (SGLT2Is n = 12,399, HR 0.90, 95% CI 0.81-1.01; GLP-1RAs n = 12,515, HR 0.95, 95% CI 0.83- 1.09) and in Europe (SGLT2Is n = 19,435, HR 0.93, 95% CI 0.85-1.02; GLP-1RAs n = 22,812, HR 0.88, 95% CI 0.79-0.99) were numerically lower but not statistically different to the rest of the world (ROW) (SGLT2Is n = 15,127, HR 0.83, 95% CI 0.75-0.92, p-value for interaction 0.26; GLP-1RAs n = 17,494, HR 0.82, 95% CI 0.73-0.92, p-value for interaction 0.28). Effects of SGLT2Is on heart failure readmission or CV death varied significantly by region (P = 0.0094). The effect of SGLT2Is was significantly smaller in Europe (n = 18,653, HR 0.86, 95% CI 0.78-0.95) than in the ROW (n = 12,463, HR 0.68, 95% CI 0.61-0.76, P = 0.0024). The smaller effect in North America (n = 9776, HR 0.76, 95% CI 0.66-0.87) did not differ significantly from that in the ROW (P = 0.2370). CONCLUSION The effects of SGLT2Is on HF events are larger in the ROW. Further analyses and studies are needed to better elucidate the differential effects of SGLTIs and GLP-1RAs by geographical regions.
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Effects of Sodium/Glucose Cotransporter 2 (SGLT2) Inhibitors on Cardiovascular and Metabolic Outcomes in Patients Without Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized-Controlled Trials.
Teo, YH, Teo, YN, Syn, NL, Kow, CS, Yoong, CSY, Tan, BYQ, Yeo, TC, Lee, CH, Lin, W, Sia, CH
Journal of the American Heart Association. 2021;(5):e019463
Abstract
Background Recent studies have increasingly shown that sodium-glucose cotransporter 2 (SGLT2) inhibitors may have beneficial cardiovascular and metabolic effects in patients without diabetes mellitus. Hence, we conducted a systematic review and meta-analysis to determine the effect of SGLT2 inhibitors on cardiovascular and metabolic outcomes in patients without diabetes mellitus. Methods and Results Four electronic databases (PubMed, Embase, Cochrane, and SCOPUS) were searched on August 30, 2020 for articles published from January 1, 2000 to August 30, 2020, for studies that examined the effect of SGLT2 inhibitors on cardiovascular and metabolic outcomes in patients without diabetes mellitus. A random-effects pairwise meta-analysis model was used to summarize the studies. A total of 8 randomized-controlled trials were included with a combined cohort of 5233 patients. In patients without diabetes mellitus, those with heart failure treated with SGLT2 inhibitors had a 20% relative risk reduction in cardiovascular deaths and heart failure hospitalizations, compared with those who were not treated (risk ratio, 0.78; P<0.001). We additionally found that treatment with SGLT2 inhibitors improved multiple metabolic indices. Patients on SGLT2 inhibitors had a reduction in body weight of -1.21 kg (P<0.001), body mass index of -0.47 kg/m2 (P<0.001), systolic blood pressure of -1.90 mm Hg (P=0.04), and fasting plasma glucose of -0.38 mmol/L (P=0.05), compared with those without. There were no between-group differences in NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels, waist circumference, diastolic blood pressure, glycated hemoglobin, low-density lipoprotein cholesterol levels, and estimated glomerular filtration rates. Across our combined cohort of 5233 patients, hypoglycemia was reported in 22 patients. Conclusions SGLT2 inhibitors improve cardiovascular outcomes in patients without diabetes mellitus with heart failure. In patients without diabetes mellitus, SGLT2 inhibitors showed positive metabolic outcomes in weight and blood pressure control.
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Do SGLT-2 inhibitors exhibit similar cardiovascular benefit in patients with heart failure with reduced or preserved ejection fraction?
Singh, AK, Singh, R, Misra, A
Journal of diabetes. 2021;(7):596-600
Abstract
Highlights The beneficial cardiovascular (CV) effects of SGLT-2 inhibitors (SGLT-2i) in patients with heart failure are already known. Whether SGLT-2i exert similar CV effects in heart failure with reduced or preserved ejection fraction is not known. This meta-analysis showed SGLT-2i exert similar CV benefits irrespective of the types of heart failure. Future trials will confirm or refute the CV effects of SGLT-2i in patients with heart failure with preserved ejection fraction.
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Sotagliflozin Reduces HF Events in T2DM Regardless of Baseline Characteristics, Including HF, CKD and LVEF.
Zhao, LM, Ding, LL, Zhan, ZL, Qiu, M
Cardiovascular drugs and therapy. 2021;(5):1077-1078