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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
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Physical activity and the risk of heart failure: a systematic review and dose-response meta-analysis of prospective studies.
Aune, D, Schlesinger, S, Leitzmann, MF, Tonstad, S, Norat, T, Riboli, E, Vatten, LJ
European journal of epidemiology. 2021;(4):367-381
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Abstract
Although physical activity is an established protective factor for cardiovascular diseases such as ischemic heart disease and stroke, less is known with regard to the association between specific domains of physical activity and heart failure, as well as the association between cardiorespiratory fitness and heart failure. We conducted a systematic review and meta-analysis of prospective observational studies to clarify the relations of total physical activity, domains of physical activity and cardiorespiratory fitness to risk of heart failure. PubMed and Embase databases were searched up to January 14th, 2020. Summary relative risks (RRs) were calculated using random effects models. Twenty-nine prospective studies (36 publications) were included in the review. The summary RRs for high versus low levels were 0.77 (95% CI 0.70-0.85, I2 = 49%, n = 7) for total physical activity, 0.74 (95% CI 0.68-0.81, I2 = 88.1%, n = 16) for leisure-time activity, 0.66 (95% CI 0.59-0.74, I2 = 0%, n = 2) for vigorous activity, 0.81 (95% CI 0.69-0.94, I2 = 86%, n = 3) for walking and bicycling combined, 0.90 (95% CI 0.86-0.95, I2 = 0%, n = 3) for occupational activity, and 0.31 (95% CI 0.19-0.49, I2 = 96%, n = 6) for cardiorespiratory fitness. In dose-response analyses, the summary RRs were 0.89 (95% CI 0.83-0.95, I2 = 67%, n = 4) per 20 MET-hours per day of total activity and 0.71 (95% CI 0.65-0.78, I2 = 85%, n = 11) per 20 MET-hours per week of leisure-time activity. Nonlinear associations were observed in both analyses with a flattening of the dose-response curve at 15-20 MET-hours/week for leisure-time activity. These findings suggest that high levels of total physical activity, leisure-time activity, vigorous activity, occupational activity, walking and bicycling combined and cardiorespiratory fitness are associated with reduced risk of developing heart failure.
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Levosimendan Can Improve the Level of B-Type Natriuretic Peptide and the Left Ventricular Ejection Fraction of Patients with Advanced Heart Failure: A Meta-analysis of Randomized Controlled Trials.
Cui, D, Liao, Y, Li, G, Chen, Y
American journal of cardiovascular drugs : drugs, devices, and other interventions. 2021;(1):73-81
Abstract
BACKGROUND AND AIMS Levosimendan, a calcium (Ca2+)-sensitizing cardiotonic agent, is mainly used in patients with advanced heart failure. However, no research could explain how levosimendan reduces the mortality in advanced heart failure patients. We aim to illustrate the efficacy of levosimendan through clinical indexes. METHODS We searched PubMed, Embase, and CENTRAL from 1994 to August 2019 to compare the efficacy of levosimendan infusion for the treatment of advanced heart failure with that of other agents (placebo, dobutamine, furosemide, and prostaglandin E1). Levels of B-type natriuretic peptide (BNP) and N-terminal pro BNP (NT-proBNP), and left ventricular ejection fraction (LVEF) and heart rate (HR) were analyzed. The count data were analyzed by the standardized mean difference (SMD) and its 95% confidence interval (CI) to determine the effect size. We chose the random effect model or the fixed effect model according to the heterogeneity. RESULTS Nine randomized controlled trials with 413 patients were ultimately enrolled. Compared with other agents (placebo, dobutamine, furosemide, and prostaglandin E1), levosimendan significantly reduced the BNP level (SMD - 0.91; 95% CI - 1.44 to - 0.39; p = 0.001; I2 = 74.3%) and improved the LVEF (SMD 0.74; 95% CI 0.22-1.25; p = 0.005; I2 = 79.7%). However, levosimendan did not significantly change the HR (SMD 0.09; 95% CI - 0.24 to 0.42; p = 0.592; I2 = 51.5%). Meanwhile, we found that the main source of heterogeneity was the use of loaded or unloaded levosimendan. CONCLUSION Our meta-analysis suggests that intravenous levosimendan can reduce BNP level and increase LVEF in patients with advanced heart failure to reduce the mortality at the shortest follow-up available.
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Simultaneous Use of Hypertonic Saline and IV Furosemide for Fluid Overload: A Systematic Review and Meta-Analysis.
Liu, C, Peng, Z, Gao, X, Gajic, O, Dong, Y, Prokop, LJ, Murad, MH, Kashani, KB, Domecq, JP
Critical care medicine. 2021;(11):e1163-e1175
Abstract
OBJECTIVES To evaluate the efficacy of the simultaneous hypertonic saline solution and IV furosemide (HSS+Fx) for patients with fluid overload compared with IV furosemide alone (Fx). DATA SOURCES Electronic databases (MEDLINE, EMBASE, CENTRAL, Cochrane Database of Systematic Reviews, PsycINFO, Scopus, and WOS) were searched from inception to March 2020. STUDY SELECTION Randomized controlled trials on the use of HSS+Fx in adult patients with fluid overload versus Fx were included. DATA EXTRACTION Data were collected on all-cause mortality, hospital length of stay, heart failure-related readmission, along with inpatient weight loss, change of daily diuresis, serum creatinine, and 24-hour urine sodium excretion from prior to post intervention. Pooled analysis with random effects models yielded relative risk or mean difference with 95% CIs. DATA SYNTHESIS Eleven randomized controlled trials comprising 2,987 acute decompensated heart failure patients were included. Meta-analysis demonstrated that HSS+Fx was associated with lower all-cause mortality (relative risk, 0.55; 95% CI, 0.46-0.67; p < 0.05; I2 = 12%) and heart failure-related readmissions (relative risk, 0.50; 95% CI, 0.33-0.76; p < 0.05; I2 = 61%), shorter hospital length of stay (mean difference, -3.28 d; 95% CI, -4.14 to -2.43; p < 0.05; I2 = 93%), increased daily diuresis (mean difference, 583.87 mL; 95% CI, 504.92-662.81; p < 0.05; I2 = 76%), weight loss (mean difference, -1.76 kg; 95% CI, -2.52 to -1.00; p < 0.05; I2 = 57%), serum sodium change (mean difference, 6.89 mEq/L; 95% CI, 4.98-8.79; p < 0.05; I2 = 95%), and higher 24-hour urine sodium excretion (mean difference, 61.10 mEq; 95% CI, 51.47-70.73; p < 0.05; I2 = 95%), along with decreased serum creatinine (mean difference, -0.46 mg/dL; 95% CI, -0.51 to -0.41; p < 0.05; I2 = 89%) when compared with Fx. The Grading of Recommendation, Assessment, Development, and Evaluation certainty of evidence ranged from low to moderate. CONCLUSIONS Benefits of the HSS+Fx over Fx were observed across all examined outcomes in acute decompensated heart failure patients with fluid overload. There is at least moderate certainty that HSS+Fx is associated with a reduction in mortality in patients with acute decompensated heart failure. Factors associated with a successful HSS+Fx utilization are still unknown. Current evidence cannot be extrapolated to other than fluid overload states in acute decompensated heart failure.
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Patients With Type 2 Diabetes Mellitus and Heart Failure Benefit More From Sodium-Glucose Cotransporter 2 Inhibitor: A Systematic Review and Meta-Analysis.
Chen, C, Peng, H, Li, M, Lu, X, Huang, M, Zeng, Y, Dong, G
Frontiers in endocrinology. 2021;:664533
Abstract
BACKGROUND Patients with type 2 diabetes mellitus (T2DM) and heart failure (HF) are at higher risk of mortality and hospitalization for heart failure (HHF). A recent study showed that sodium-glucose cotransporter 2 (SGLT-2) inhibitors may be a promising choice. METHODS We searched the PubMed, Embase, and Cochrane databases of clinical trials for randomized controlled trials investigating the long-term effects of SGLT-2 inhibitors in patients with T2DM and HF compared with placebo. The primary outcome was cardiovascular death or HHF, and the secondary outcomes included cardiovascular death (CV death), HHF, and all-cause mortality. We also conducted an exploratory analysis and tried to identify the population, which will benefit more from the treatment. RESULTS After the study selection, a total of 5 trials, including 4 subgroup analyses, met the eligibility criteria. The results suggested that the use of SGLT-2 inhibitors was associated with a reduction in the incidence of CV death or HHF (HR, 0.69[95%CI, 0.63-0.77], P<0.00001), CV death (HR, 0.80[95%CI, 0.69-0.92], P = 0.001), HHF (HR, 0.67[95%CI, 0.60-0.76], P < 0.00001), and all-cause mortality (HR, 0.74[95%CI, 0.64-0.86], P < 0.0001). Moreover, patients with T2DM and HF may benefit more from the treatment than those with T2DM/HF. CONCLUSION The long-term use of SGLT-2 inhibitors can help reduce the risk of mortality and HHF in patients with T2DM and HF. SYSTEMATIC REVIEW REGISTRATION PROSPERO [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021233156], identifier [CRD42021233156].
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Association of SGLT2 Inhibitors With Cardiovascular and Kidney Outcomes in Patients With Type 2 Diabetes: A Meta-analysis.
McGuire, DK, Shih, WJ, Cosentino, F, Charbonnel, B, Cherney, DZI, Dagogo-Jack, S, Pratley, R, Greenberg, M, Wang, S, Huyck, S, et al
JAMA cardiology. 2021;(2):148-158
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Abstract
IMPORTANCE Sodium-glucose cotransporter 2 (SGLT2) inhibitors favorably affect cardiovascular (CV) and kidney outcomes; however, the consistency of outcomes across the class remains uncertain. OBJECTIVE To perform meta-analyses that assess the CV and kidney outcomes of all 4 available SGLT2 inhibitors in patients with type 2 diabetes. DATA SOURCES A systematic literature search was conducted in PubMed from January 1, 2015, to January 31, 2020. STUDY SELECTION One hundred forty-five records were initially identified; 137 were excluded because of study design or topic of interest. As a result, a total of 6 randomized, placebo-controlled CV and kidney outcomes trials of SGLT2 inhibitors in patients with type 2 diabetes were identified, with contributory data from 9 publications. All analyses were conducted on the total patient population of these trials. DATA EXTRACTION AND SYNTHESIS Standardized data search and abstraction were performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) Statement. Data were analyzed using a fixed-effect model. MAIN OUTCOMES AND MEASURES Outcomes included time to the first event of (1) the composite of major adverse CV events of myocardial infarction, stroke, or CV death, and each component, (2) the composite of hospitalization for heart failure (HHF) or CV death (HHF/CV death) and each component, and (3) kidney composite outcomes. For outcomes in the overall trial populations and in selected subgroups, hazard ratios (HRs) and 95% CIs were pooled and meta-analyzed across trials. RESULTS Data from 6 trials comprised 46 969 unique patients with type 2 diabetes, including 31 116 (66.2%) with atherosclerotic CV disease. The mean (SD) age of all trial participants was 63.7 (7.9) years; 30 939 (65.9%) were men, and 36 849 (78.5%) were White. The median number of participants per trial was 8246 (range, 4401-17 160). Overall, SGLT2 inhibitors were associated with a reduced risk of major adverse CV events (HR, 0.90; 95% CI, 0.85-0.95; Q statistic, P = .27), HHF/CV death (HR, 0.78; 95% CI, 0.73-0.84; Q statistic, P = .09), and kidney outcomes (HR, 0.62; 95% CI, 0.56-0.70; Q statistic, P = .09), with no significant heterogeneity of associations with outcome. Associated risk reduction for HHF was consistent across the trials (HR, 0.68; 95% CI, 0.61-0.76; I2 = 0.0%), whereas significant heterogeneity of associations with outcome was observed for CV death (HR, 0.85; 95% CI, 0.78-0.93; Q statistic, P = .02; I2 = 64.3%). The presence or absence of atherosclerotic CV disease did not modify the association with outcomes for major adverse CV events (HR, 0.89; 95% CI, 0.84-0.95 and HR, 0.94; 95% CI, 0.83-1.07, respectively; P = .63 for interaction), with similar absence of associations with outcome modification by prevalent atherosclerotic CV disease for HHF/CV death (P = .62 for interaction), HHF (P = .26 for interaction), or kidney outcomes (P = .73 for interaction). CONCLUSIONS AND RELEVANCE In this meta-analysis, SGLT2 inhibitors were associated with a reduced risk of major adverse CV events; in addition, results suggest significant heterogeneity in associations with CV death. The largest benefit across the class was for an associated reduction in risk for HHF and kidney outcomes, with benefits for HHF risk being the most consistent observation across the trials.
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Efficacy and safety of sacubitril-valsartan in patients with heart failure: a systematic review and meta-analysis of randomized clinical trials: A PRISMA-compliant article.
Lin, J, Zhou, J, Xie, G, Liu, J
Medicine. 2021;(52):e28231
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Abstract
BACKGROUND To investigate the efficacy and safety of sacubitril-valsartan in patients with heart failure, relevant randomized clinical trials (RCTs) were analyzed. METHODS We used Cochrane Library, PubMed web of science, CNKI, VIP, Medline, ISI Web of Science, CBMdisc, and Wanfang database to conduct a systematic literature research. A fixed-effects model was used to evaluate the standardized mean differences (SMDs) with 95% confidence intervals. We conducted sensitivity analysis and analyzed publication bias to comprehensively estimate the efficacy and safety of sacubitril-valsartan in patients with heart failure. RESULTS Among 132 retrieved studies, 5 relevant RCTs were included in the meta-analysis. The result showed that left ventricular ejection fraction (LVEF) was improved after sacubitril-valsartan in patients with heart failure, with an SMD (95% CI of 1.1 [1.01, 1.19] and P < .00001 fixed-effects model). Combined outcome indicators showed that, combined outcome indicators showed that, compared with control group, the left ventricular volume index (LAVI) (WMD = -2.18, 95% CI [-3.63, -0.74], P = .003), the E/e' (WMD = -1.01, 95% CI [-1.89, -0.12], P = .03), the cardiovascular death (RR = 0.89, 95% CI [0.83, 0.96], P = .003], and the rehospitalization rate of heart failure (RR = 0.83, 95% CI [0.78, 0.88], P < .01) decreased more significantly, but it had no effect on renal function (WMD = 0.74, 95% CI [0.54, 1.01], P = .06). CONCLUSIONS The present meta-analysis suggested that sacubitril-valsartan may improve the cardiac function of heart failure. Given the limited number of included studies, additional large sample-size RCTs are required to determine the long-term effect of cardiac function of sacubitril-valsartan in patients with heart failure.
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Comparing the clinical outcomes across different sodium/glucose cotransporter 2 (SGLT2) inhibitors in heart failure patients: a systematic review and network meta-analysis of randomized controlled trials.
Teo, YH, Yoong, CSY, Syn, NL, Teo, YN, Cheong, JYA, Lim, YC, Lee, CH, Yeo, TC, Chai, P, Wong, RCC, et al
European journal of clinical pharmacology. 2021;(10):1453-1464
Abstract
PURPOSE Empagliflozin, dapagliflozin, canagliflozin, and ertugliflozin have been shown in randomized controlled trials to improve cardiovascular, metabolic, and renal outcomes in heart failure patients. To date, there has not been any meta-analysis examining the differences in clinical outcomes across different SGLT2 inhibitors in heart failure patients. METHODS Four electronic databases (PubMed, Embase, Cochrane, SCOPUS) were searched on 13 September 2020 for articles published from 1 January 2000 to 13 September 2020 examining the effect of SGLT2 inhibitors on cardiovascular, renal, and metabolic outcomes in heart failure patients. Frequentist network meta-analysis was performed on extracted data. RESULTS Ten randomized controlled trials were included with a combined cohort of 15,373 patients. In heart failure patients, frequentist network meta-analysis demonstrated no demonstrable difference in treatment effect across the SGLT2 inhibitors for heart failure hospitalization, cardiovascular deaths, composite of cardiovascular deaths and heart failure hospitalizations, all-cause mortality, and a composite of cardiovascular deaths and non-fatal myocardial infarction and non-fatal stroke. There was no demonstrable difference in treatment effect for worsening renal function or the weighted mean difference for weight, hemoglobin A1c, and systolic blood pressure. CONCLUSIONS There were no demonstrable treatment differences across SGLT2 inhibitors across cardiovascular, renal, and metabolic outcomes, although this needs to be interpreted considering the wide confidence intervals, limited number of included studies, and heterogeneity present. Future research of different SGLT2 inhibitors in head-to-head studies is warranted to determine if there is a drug class effect.
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Meta-Analysis of Sodium-Glucose Cotransporter 2 Inhibitors in Heart Failure Patients Without Diabetes.
Mohamed, MMG, Shaikh, S, Osman, M, Kheiri, B
The American journal of cardiology. 2021;:175-176
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Intravenous iron for heart failure with evidence of iron deficiency: a meta-analysis of randomised trials.
Graham, FJ, Pellicori, P, Ford, I, Petrie, MC, Kalra, PR, Cleland, JGF
Clinical research in cardiology : official journal of the German Cardiac Society. 2021;(8):1299-1307
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Abstract
BACKGROUND The recent AFFIRM-AHF trial assessing the effect of intravenous (IV) iron on outcomes in patients hospitalised with worsening heart failure who had iron deficiency (ID) narrowly missed its primary efficacy endpoint of recurrent hospitalisations for heart failure (HHF) or cardiovascular (CV) death. We conducted a meta-analysis to determine whether these results were consistent with previous trials. METHODS We searched for randomised trials of patients with heart failure investigating the effect of IV iron vs placebo/control groups that reported HHF and CV mortality from 1st January 2000 to 5th December 2020. Seven trials were identified and included in this analysis. A fixed effect model was applied to assess the effects of IV iron on the composite of first HHF or CV mortality and individual components of these. RESULTS Altogether, 2,166 patients were included (n = 1168 assigned to IV iron; n = 998 assigned to control). IV iron reduced the composite of HHF or CV mortality substantially [OR 0.73; (95% confidence interval 0.59-0.90); p = 0.003]. Outcomes were consistent for the pooled trials prior to AFFIRM-AHF. Whereas first HHF were reduced substantially [OR 0.67; (0.54-0.85); p = 0.0007], the effect on CV mortality was uncertain but appeared smaller [OR 0.89; (0.66-1.21); p = 0.47]. CONCLUSION Administration of IV iron to patients with heart failure and ID reduces the risk of the composite outcome of first heart failure hospitalisation or cardiovascular mortality, but this outcome may be driven predominantly by an effect on HHF. At least three more substantial trials of intravenous iron are underway.