Association of SGLT2 Inhibitors With Cardiovascular and Kidney Outcomes in Patients With Type 2 Diabetes: A Meta-analysis.
Association of SGLT2 Inhibitors With Cardiovascular and Kidney Outcomes in Patients With Type 2 Diabetes: A Meta-analysis.
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DOI：
10.1001/jamacardio.2020.4511
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发表时间：
2021-02-01
期刊：
影响因子：
24
通讯作者：
Cannon CP
中科院分区：
文献类型：
--
作者：
McGuire DK;Shih WJ;Cosentino F;Charbonnel B;Cherney DZI;Dagogo-Jack S;Pratley R;Greenberg M;Wang S;Huyck S;Gantz I;Terra SG;Masiukiewicz U;Cannon CP
这项荟萃分析使用了来自6项结局试验的2型糖尿病患者的数据，以研究钠-葡萄糖协同转运蛋白2抑制剂与心血管和肾脏疾病相关结局的相关性。钠-葡萄糖协同转运蛋白2（SGLT 2）抑制剂对心血管和肾脏相关结局的有效性在总体药物类别中是否相似，以及是否存在流行的心血管和慢性肾脏疾病？对4种SGLT 2抑制剂的6项结局试验进行的荟萃分析结果表明，主要心血管不良事件的风险降低和心血管死亡的异质性相关。最大程度的获益是降低因心力衰竭（HHF）和肾脏疾病进展住院的风险，HHF风险结局的估计值是试验中最一致的观察结果。这些结果表明，SGLT 2抑制剂与心血管死亡结局的相关性具有一定的异质性，该类药物中有利的HHF和肾脏疾病结局一致。钠-葡萄糖协同转运蛋白2（SGLT 2）抑制剂对心血管（CV）和肾脏结局有有利影响;然而，该类药物结局的一致性仍不确定。进行荟萃分析，评估所有4种可用SGLT 2抑制剂在2型糖尿病患者中的CV和肾脏结局。从2015年1月1日至2020年1月31日，在PubMed中进行了系统性文献检索。最初确定了145条记录;由于研究设计或感兴趣的主题，排除了137条记录。因此，共确定了6项SGLT 2抑制剂治疗2型糖尿病患者的随机、安慰剂对照CV和肾脏结局试验，贡献数据来自9篇出版物。所有分析均针对这些试验的总患者人群进行。按照系统性综述和荟萃分析（PRISMA）声明的首选报告项目进行标准化数据检索和提取。使用固定效应模型分析数据。结局包括至以下事件首次发生的时间：（1）心肌梗死、卒中或CV死亡等重大CV不良事件和各组分的复合事件，（2）因心力衰竭（HHF）或CV死亡（HHF/CV死亡）住院治疗和各组分的复合事件，以及（3）肾脏复合结局。对于总体试验人群和选定亚组的结局，汇总了风险比（HR）和95% CI，并对各试验进行了荟萃分析。来自6项试验的数据包括46969例独特的2型糖尿病患者，其中31116例（66.2%）患有动脉粥样硬化性CV疾病。所有试验参与者的平均（SD）年龄为63.7（7.9）岁; 30939（65.9%）例为男性，36849（78.5%）例为白色。每项试验的中位参与者人数为8246（范围：4401- 17160）。总体而言，SGLT 2抑制剂与重大不良CV事件风险降低相关（HR，0.90; 95% CI，0.85-0.95; Q统计量，P = .27），HHF/CV死亡（HR，0.78; 95% CI，0.73-0.84; Q统计，P = 0.09）和肾脏结局（HR，0.62; 95% CI，0.56-0.70; Q统计，P = 0.09），与结局相关性无显著异质性。HHF的相关风险降低在各试验中一致（HR，0.68; 95% CI，0.61-0.76; I2 = 0.0%），而CV死亡与结局的相关性具有显著异质性（HR，0.85; 95% CI，0.78-0.93; Q统计量，P = 0.02; I2 = 64.3%）。存在或不存在动脉粥样硬化性CV疾病并不能改变与主要不良CV事件结局的相关性（HR，0.89; 95% CI，0.84-0.95; HR，0.94; 95% CI，0.83-1.07; P = 0.63（相互作用），HHF/CV死亡与流行性动脉粥样硬化性CV疾病的结局改变无类似相关性（相互作用P = 0.62）、HHF（相互作用P = 0.26）或肾脏结局（相互作用P = 0.73）。在这项荟萃分析中，SGLT 2抑制剂与重大不良CV事件风险降低相关;此外，结果表明与CV死亡相关性存在显著异质性。该类中最大的获益是HHF和肾脏结局风险的相关降低，HHF风险获益是试验中最一致的观察结果。
This meta-analysis uses data from patients with type 2 diabetes from 6 outcomes trials to investigate the association of sodium-glucose cotransporter 2 inhibitors with cardiovascular- and kidney disease–related outcomes. Is the effectiveness of sodium-glucose cotransporter 2 (SGLT2) inhibitors on cardiovascular- and kidney-related outcomes similar across the class of medications overall and by the presence or absence of prevalent cardiovascular and chronic kidney disease? Results from a meta-analysis of 6 outcomes trials of 4 SGLT2 inhibitors suggest an associated reduction in risk of major adverse cardiovascular events and heterogeneity of cardiovascular death. The greatest magnitude of benefit was for reduction in risk for hospitalization for heart failure (HHF) and kidney disease progression, with estimates of HHF risk outcome the most consistent observation across the trials. These findings suggest that SGLT2 inhibitors have some heterogeneity of associations with outcomes for cardiovascular death, with consistency of favorable HHF and kidney disease outcomes across the class. Sodium-glucose cotransporter 2 (SGLT2) inhibitors favorably affect cardiovascular (CV) and kidney outcomes; however, the consistency of outcomes across the class remains uncertain. To perform meta-analyses that assess the CV and kidney outcomes of all 4 available SGLT2 inhibitors in patients with type 2 diabetes. A systematic literature search was conducted in PubMed from January 1, 2015, to January 31, 2020. 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. 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. 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. 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). 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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影响因子：
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作者：
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通讯作者：
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