Heterogeneity in cardiorenal protection by Sodium glucose cotransporter 2 inhibitors in heart failure across the ejection fraction strata: Systematic review and meta-analysis

Saeed Taheri
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Abstract

BACKGROUND Gliflozins or Sodium glucose cotransporter 2 inhibitors (SGLT2i) are relatively novel antidiabetic medications that have recently been shown to represent favorable effects on patients’ cardiorenal outcomes. However, there is shortage of data on potential disparities in this therapeutic effect across different patient subpopulations. AIM To investigate differential effects of SGLT2i on the cardiorenal outcomes of heart failure patients across left ventricular ejection fraction (LVEF) levels. METHODS Literature was searched systematically for the large randomized double-blind controlled trials with long enough follow up periods reporting cardiovascular and renal outcomes in their patients regarding heart failure status and LVEF levels. Data were then meta-analyzed after stratification of the pooled data across the LVEF strata and New York Heart Associations (NYHA) classifications for heart failure using Stata software version 17.0. RESULTS The literature search returned 13 Large clinical trials and 13 post hoc analysis reports. Meta-analysis of the effects of gliflozins on the primary composite outcome showed no significant difference in efficacy across the heart failure subtypes, but higher efficacy were detected in patient groups at lower NYHA classifications (I 2 = 46%, P = 0.02). Meta-analyses across the LVEF stratums revealed that a baseline LVEF lower than 30% was associated with enhanced improvement in the primary composite outcome compared to patients with higher LVEF levels at the borderline statistical significance (HR: 0.70, 95%CI: 0.60 to 0.79 vs 0.81, 95%CI: 0.75 to 0.87; respectively, P = 0.06). Composite renal outcome was improved significantly higher in patients with no heart failure than in heart failure patients with preserved ejection fraction (HFpEF) (HR: 0.60, 95%CI: 0.49 to 0.72 vs 0.94, 95%CI: 0.74 to 1.13; P = 0.04). Acute renal injury occurred significantly less frequently in heart failure patients with reduced ejection fraction who received gliflozins than in HFpEF (HR: 0.67, 95%CI: 51 to 0.82 vs 0.94, 95%CI: 0.82 to 1.06; P = 0.01). Volume depletion was consistently increased in response to SGLT2i in all the subgroups. CONCLUSION Heart failure patients with lower LVEF and lower NYHA sub-classifications were found to be generally more likely to benefit from therapy with gliflozins. Further research are required to identify patient subgroups representing the highest benefits or adverse events in response to SGLT2i.
葡萄糖钠共转运体 2 抑制剂在不同射血分数阶层对心力衰竭患者心肾保护的异质性:系统回顾和荟萃分析
背景 Gliflozins 或葡萄糖钠共转运体 2 抑制剂(SGLT2i)是一种相对新型的抗糖尿病药物,近来已被证明对患者的心肾功能有良好的影响。然而,关于不同患者亚群在这种治疗效果上的潜在差异,目前还缺乏相关数据。目的 探讨不同左心室射血分数(LVEF)水平的 SGLT2i 对心衰患者心肾功能预后的不同影响。方法 系统地检索了具有足够长随访期的大型随机双盲对照试验的文献,这些试验报告了心衰状态和 LVEF 水平下患者的心血管和肾脏疗效。然后使用 Stata 软件 17.0 版对 LVEF 分层和纽约心脏协会(NYHA)心衰分类的汇总数据进行分层后进行元分析。结果 文献检索结果显示有 13 项大型临床试验和 13 项事后分析报告。格列酮嗪对主要综合结果影响的 Meta 分析表明,不同心衰亚型的疗效无显著差异,但在 NYHA 分级较低的患者组中发现了更高的疗效(I 2 = 46%,P = 0.02)。对 LVEF 分层进行的 Meta 分析显示,与 LVEF 水平较高的患者相比,基线 LVEF 低于 30% 的患者的主要复合结局改善程度更高,但在统计学上有边缘显著性(HR:0.70,95%CI:0.60 至 0.79 vs 0.81,95%CI:0.75 至 0.87;分别为 P = 0.06)。与射血分数保留的心衰患者(HFpEF)相比,无心衰患者的综合肾功能改善率明显更高(HR:0.60,95%CI:0.49 至 0.72 vs 0.94,95%CI:0.74 至 1.13;P = 0.04)。与 HFpEF 相比,射血分数降低的心衰患者接受格列酮类药物治疗后,急性肾损伤的发生率明显降低(HR:0.67,95%CI:51 至 0.82 vs 0.94,95%CI:0.82 至 1.06;P = 0.01)。所有亚组患者对 SGLT2i 的反应中,血容量耗竭持续增加。结论 LVEF 较低和 NYHA 分级较低的心衰患者一般更容易从格列奈类治疗中获益。还需要进一步研究,以确定哪些亚组患者服用 SGLT2i 后获益最大,哪些亚组患者服用 SGLT2i 后不良反应最多。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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