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Iron therapy in iron-deficiency patients with heart failure with preserved ejection fraction: A protocol for meta-analysis.
Fukuta, H, Hagiwara, H, Kamiya, T
Medicine. 2021;(32):e26919
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Abstract
BACKGROUND Nearly half of patients with heart failure (HF) have preserved ejection fraction (EF) and the mortality and morbidity of patients with HF with preserved EF (HFpEF) are high. However, there is no established therapy to improve survival in these patients. HFpEF patients are often elderly and their primary chronic symptom is severe exercise intolerance. Thus, improvement of exercise capacity presents another important clinical outcome in HFpEF patients. Iron deficiency is common in HF patients, and the presence of iron deficiency, regardless of concomitant anemia, is associated with worse symptoms, impaired exercise capacity, and higher mortality and hospitalization in these patients. Several meta-analyses of randomized controlled trials reported that iron administration improved HF symptoms, exercise capacity, and clinical outcomes in iron-deficiency patients with HF with reduced EF. However, there is insufficient evidence as to the effect of iron administration in iron-deficiency HFpEF patients. METHODS AND RESULTS This meta-analysis will include randomized controlled trials on the effects of iron administration on HF symptoms, exercise capacity, and health-related quality of life in iron-deficiency HFpEF patients. Information of studies will be collected from PubMed, Web of Science, Cochrane Library, and ClinicalTrials.gov. The primary outcome will be exercise capacity (6-minute walking distance). The secondary outcomes will be HF symptoms, health-related quality of life, and mortality and hospitalization rates. CONCLUSION This meta-analysis will evaluate the effect of iron therapy in iron-deficiency HFpEF patients, providing evidence as to the iron administration in these patients. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42020205297.
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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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Efficacy of Trimetazidine in Limiting Periprocedural Myocardial Injury in Patients Undergoing Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis.
Wang, C, Chen, W, Yu, M, Yang, P
Angiology. 2021;(6):511-523
Abstract
We systematically searched the literature to assess the efficacy of trimetazidine in reducing periprocedural myocardial injury and improving postoperative left ventricular ejection fraction (LVEF) in patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI). An electronic search was conducted based on the PubMed, Ovid, Scopus, Springer, CENTRAL, and Google Scholar databases; 14 randomized controlled trials (RCTs) were included. Our meta-analysis showed a significant reduction in cardiac troponin I (cTnI) levels with trimetazidine compared with controls (P < .00001) but not in serum creatine kinase-myocardial band levels (P = .49). There were significantly reduced odds of ischemic ST-T segment changes with trimetazidine (P = .0.03) but lack of significant difference in the incidence of anginal attacks between the 2 groups (P = .10). Results also suggest significantly higher LVEF with trimetazidine compared with controls (P < .00001). Meta-regression analysis indicated no influence of duration of trimetazidine therapy on cTnI levels. The administration of preprocedure trimetazidine may have a role in reducing periprocedural myocardial injury in patients with CAD undergoing PCI. Evidence also suggests that postoperative trimetazidine may improve LVEF in the short term. Lack of high-quality trials and the heterogeneity of studies limit the ability of our analysis to draw strong conclusions. Further well-designed RCTs are required to supplement current evidence.
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Meta-Analysis Assessing the Cardiovascular Efficacy of Sodium-Glucose Co-Transporter-2 Inhibitors According to Baseline Treatment of Interest.
Patoulias, D, Papadopoulos, C, Katsimardou, A, Doumas, M
The American journal of cardiology. 2021;:134-136
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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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Meta-Analysis of Antithrombotic Strategies in Patients With Heart Failure With Reduced Ejection Fraction and Sinus Rhythm.
Ueyama, H, Takagi, H, Briasoulis, A, Harrington, M, Steinberg, D, Kuno, T
The American journal of cardiology. 2020;:92-98
Abstract
Heart failure with reduced ejection fraction (HFrEF) is associated with an increased risk of thrombotic events. We compared the safety and efficacy of different antithrombotic strategies for HFrEF and sinus rhythm. PubMed and Embase were searched through January 2020 for studies comparing oral anticoagulants versus antiplatelet agents or placebo in HFrEF and sinus rhythm to include in this network meta-analysis. We identified 5 randomized controlled trials with a total of 9,390 patients randomized to low dose rivaroxaban, vitamin K antagonist (VKA), antiplatelets, or placebo. Low dose rivaroxaban and VKA did not show a significant decrease in stroke compared with placebo but were associated with an increased risk of major bleeding (risk ratio [RR] 6.86, 95% confidence interval [CI] 1.16 to 40.7; RR 8.62, 95% CI 1.52 to 48.9, respectively). When compared with antiplatelets, low dose rivaroxaban and VKA were associated with a significantly decreased risk of stroke (RR 0.67, 95% CI 0.47 to 0.96; RR 0.50, 95% CI 0.33 to 0.76, respectively), but with a significantly increased risk of major bleeding (RR 1.65, 95% CI 1.16 to 2.33; RR 2.07, 95% CI 1.51 to 2.84, respectively). There was no significant difference in these outcomes between low dose rivaroxaban versus VKA and antiplatelets versus placebo. There were no significant differences in all-cause mortality, myocardial infarction, or rehospitalization for heart failure among each treatment. In conclusion, in patient with HFrEF and sinus rhythm, use of oral anticoagulation with or without antiplatelet agents increases the risk of bleeding without substantial effects on the risk of ischemic stroke.
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Effects of antidiabetic drugs on left ventricular function/dysfunction: a systematic review and network meta-analysis.
Zhang, DP, Xu, L, Wang, LF, Wang, HJ, Jiang, F
Cardiovascular diabetology. 2020;(1):10
Abstract
BACKGROUND Although a variety of antidiabetic drugs have significant protective action on the cardiovascular system, it is still unclear which antidiabetic drugs can improve ventricular remodeling and fundamentally delay the process of heart failure. The purpose of this network meta-analysis is to compare the efficacy of sodium glucose cotransporter type 2 (SGLT-2) inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) agonists, metformin (MET), sulfonylurea (SU) and thiazolidinediones (TZDs) in improving left ventricular (LV) remodeling in patients with type 2 diabetes (T2DM) and/or cardiovascular disease (CVD). METHODS We searched articles published before October 18, 2019, regardless of language or data, in 4 electronic databases: PubMed, EMBASE, Cochrane Library and Web of Science. We included randomized controlled trials in this network meta-analysis, as well as a small number of cohort studies. The differences in the mean changes in left ventricular echocardiographic parameters between the treatment group and control group were evaluated. RESULTS The difference in the mean change in LV ejection fraction (LVEF) between GLP-1 agonists and placebo in treatment effect was greater than zero (MD = 2.04% [0.64%, 3.43%]); similar results were observed for the difference in the mean change in LV end-diastolic diameter (LVEDD) between SGLT-2 inhibitors and placebo (MD = - 3.3 mm [5.31, - 5.29]), the difference in the mean change in LV end-systolic volume (LVESV) between GLP-1 agonists and placebo (MD = - 4.39 ml [- 8.09, - 0.7]); the difference in the mean change in E/e' between GLP-1 agonists and placebo (MD = - 1.05[- 1.78, - 0.32]); and the difference in the mean change in E/e' between SGLT-2 inhibitors and placebo (MD = - 1.91[- 3.39, - 0.43]). CONCLUSIONS GLP-1 agonists are more significantly associated with improved LVEF, LVESV and E/e', SGLT-2 inhibitors are more significantly associated with improved LVEDD and E/e', and DPP-4 inhibitors are more strongly associated with a negative impact on LV end-diastolic volume (LVEDV) than are placebos. SGLT-2 inhibitors are superior to other drugs in pairwise comparisons.
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Efficacy and Safety of Inorganic Nitrate Versus Placebo Treatment in Heart Failure with Preserved Ejection Fraction.
Gui, Y, Chen, J, Hu, J, Ouyang, M, Deng, L, Liu, L, Sun, K, Tang, Y, Xiang, Q, Xu, J, et al
Cardiovascular drugs and therapy. 2020;(4):503-513
Abstract
BACKGROUND Heart failure with preserved ejection fraction (HFpEF) is common, yet there is a lack of effective treatments. In this meta-analysis, we assessed the efficacy and safety of inorganic nitrate in patients with HFpEF. METHODS AND RESULTS We systematically searched PubMed, Embase, and the Cochrane Library from the inception of the database through March 2020. We included randomized controlled trials that compared the efficacy and safety of inorganic nitrate with a placebo in the treatment of patients with HFpEF. The primary outcome of the meta-analysis was exercise capacity (measured as a change in peak oxygen uptake). We also assessed the effect of inorganic nitrate on diastolic function (measured as changes in E/A and E/e', assessed by echocardiography), quality of life (estimated using the Kansas City Cardiomyopathy Questionnaire), and rest and exercise hemodynamics (measured by invasive cardiac catheterization). In the pooled data analysis, there were no significant differences in peak oxygen uptake (mL/kg/min) [mean difference (MD), 0.25; 95% CI, - 0.07 to 0.57], diastolic function [E/A-standardized mean difference (SMD), 0.51; 95% CI, - 0.17 to 1.20; or E/e'-SMD, 0.02; 95% CI, - 0.23 to 0.27], or quality of life. However, a significant change was observed in the rest and exercise hemodynamics between the inorganic nitrate and placebo treatment in HFpEF patients. No study has reported the effect of inorganic nitrate on hospitalization and mortality of patients with HFpEF. CONCLUSIONS In patients with HFpEF, the use of inorganic nitrate is not associated with improvements in exercise capacity, diastolic function, and quality of life but is associated with significant changes in rest and exercise hemodynamics.
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SGLT2 inhibitors in patients with heart failure with reduced ejection fraction: a meta-analysis of the EMPEROR-Reduced and DAPA-HF trials.
Zannad, F, Ferreira, JP, Pocock, SJ, Anker, SD, Butler, J, Filippatos, G, Brueckmann, M, Ofstad, AP, Pfarr, E, Jamal, W, et al
Lancet (London, England). 2020;(10254):819-829
Abstract
BACKGROUND Both DAPA-HF (assessing dapagliflozin) and EMPEROR-Reduced (assessing empagliflozin) trials showed that sodium-glucose co-transporter-2 (SGLT2) inhibition reduced the combined risk of cardiovascular death or hospitalisation for heart failure in patients with heart failure with reduced ejection fraction (HFrEF) with or without diabetes. However, neither trial was powered to assess effects on cardiovascular death or all-cause death or to characterise effects in clinically important subgroups. Using study-level published data from DAPA-HF and patient-level data from EMPEROR-Reduced, we aimed to estimate the effect of SGLT2 inhibition on fatal and non-fatal heart failure events and renal outcomes in all randomly assigned patients with HFrEF and in relevant subgroups from DAPA-HF and EMPEROR-Reduced trials. METHODS We did a prespecified meta-analysis of the two single large-scale trials assessing the effects of SGLT2 inhibitors on cardiovascular outcomes in patients with HFrEF with or without diabetes: DAPA-HF (assessing dapagliflozin) and EMPEROR-Reduced (assessing empagliflozin). The primary endpoint was time to all-cause death. Additionally, we assessed the effects of treatment in prespecified subgroups on the combined risk of cardiovascular death or hospitalisation for heart failure. These subgroups were based on type 2 diabetes status, age, sex, angiotensin receptor neprilysin inhibitor (ARNI) treatment, New York Heart Association (NYHA) functional class, race, history of hospitalisation for heart failure, estimated glomerular filtration rate (eGFR), body-mass index, and region (post-hoc). We used hazard ratios (HRs) derived from Cox proportional hazard models for time-to-first event endpoints and Cochran's Q test for treatment interactions; the analysis of recurrent events was based on rate ratios derived from the Lin-Wei-Yang-Ying model. FINDINGS Among 8474 patients combined from both trials, the estimated treatment effect was a 13% reduction in all-cause death (pooled HR 0·87, 95% CI 0·77-0·98; p=0·018) and 14% reduction in cardiovascular death (0·86, 0·76-0·98; p=0·027). SGLT2 inhibition was accompanied by a 26% relative reduction in the combined risk of cardiovascular death or first hospitalisation for heart failure (0·74, 0·68-0·82; p<0·0001), and by a 25% decrease in the composite of recurrent hospitalisations for heart failure or cardiovascular death (0·75, 0·68-0·84; p<0·0001). The risk of the composite renal endpoint was also reduced (0·62, 0·43-0·90; p=0·013). All tests for heterogeneity of effect size between trials were not significant. The pooled treatment effects showed consistent benefits for subgroups based on age, sex, diabetes, treatment with an ARNI and baseline eGFR, but suggested treatment-by-subgroup interactions for subgroups based on NYHA functional class and race. INTERPRETATION The effects of empagliflozin and dapagliflozin on hospitalisations for heart failure were consistent in the two independent trials and suggest that these agents also improve renal outcomes and reduce all-cause and cardiovascular death in patients with HFrEF. FUNDING Boehringer Ingelheim.
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Meta-analysis of Nicorandil effectiveness on myocardial protection after percutaneous coronary intervention.
Zhao, XT, Zhang, CF, Liu, QJ
BMC cardiovascular disorders. 2019;(1):144
Abstract
BACKGROUND Using the current meta-analysis as well as systematic review, to determine the curative effect of Nicorandil in comparison of no Nicorandil after elective percutaneous coronary intervention(PCI) on patients. METHODS Published literatures were identified via a computerized literature search of CENTRAL, PubMed, Cochrane, Embase Databases of Systematic Reviews. A set of randomized trials evaluating Nicorandil in comparison of no Nicorandil administered following PCI in patients harboring coronary artery disease were included. Outcomes were revealed based on the following parameters: peak creatine kinase-MB (CK-MB) value, left ventricular ejection fraction (LVEF), peak troponin I (cTnI), and major adverse cardiovascular events (MACEs) per randomized patients. RESULTS We included a total of 14 RCTs involving 1864 subjects in the present review. According to this meta-analysis, LVEF was significantly improved in Nicorandil group; the peak CK-MB level and the incidence of adverse cardiovascular events were remarkably lower in Nicorandil group. Nicorandil and no Nicorandil administered group appeared to be equivalent with regards to cTnI. CONCLUSIONS Nicorandil is effective for patients undergoing elective PCI with coronary artery disease in terms of reducing the incidence of adverse cardiovascular events as well as improving heart function. Nicorandil may exert potential role as a valid and adjunctive therapy accompanied with PCI.