背景:一些具有里程碑意义的随机对照试验(RCT)已经证明了钠-葡萄糖共转运2(SGLT2)抑制剂在降低全因死亡率方面的功效,心血管(CV)死亡率和心力衰竭(HF)住院。人们对它们的作用机制以及它们是否对逆转心脏重塑有直接影响非常感兴趣。因此,我们对安慰剂对照的RCT进行了荟萃分析,评估了SGLT2抑制对HF患者心脏逆转重构的影像学来源标志物的影响.
方法:我们根据系统评价和荟萃分析(PRISMA)声明和Cochrane协作的首选报告项目进行了系统评价和荟萃分析。包括PubMed在内的每个主要数据库的数据查询,EMBASE,进行MEDLINE和Cochrane图书馆。纳入评估18岁以上HF患者的RCT,比较SGLT2抑制剂与安慰剂对照。结果测量包括左心室舒张末期容积和容积指数(LVEDV/LVEDVi),左心室收缩末期容积和容积指数(LVSDV/LVSDVi),左心室射血分数(LVEF),左心室质量指数(LVMi),左心房容积指数(LAVi)和左心室整体纵向应变(LVGLS)。射血分数保留的HF人群的研究被排除在参数分析之外,这将受到基线LVEF的显著影响,如卷和LVEF。从每个研究中提取平均差异和标准误差,并使用随机效应模型汇集了研究中的平均差异和标准误差。进行预先指定的亚组分析,以根据使用的成像方式(心脏磁共振成像和超声心动图)对结果进行分层。本研究在PROSPERO注册:CRD42023482722。
结果:七个随机分组,纳入了由657例患者组成的HF患者的安慰剂对照试验.纳入研究的总体LVEF范围为29±8.0%至55.5±4.2%。在HFrEF参数分析的研究中,基线LVEF范围为29±8%至45.5±12%。汇总数据显示SGLT2抑制,与安慰剂对照相比,导致LVEDV的平均差[-11.62ml(95%置信区间,CI-17.90至-5.25;z=3.67,P=0.0004)],LVEDVi[-6.08ml(95%CI-9.96至-2.20;z=3.07;P=0.002)],LVESV[-12.47ml(95%CI-19.12至-5.82;z=3.68;P=0.0002)],LVESVi[-6.02ml(95%CI-10.34至-1.70;z=2.73;P=0.006)],LVM[-9.77g(95%CI-17.65至-1.89;z=2.43;P=0.02)],LVMi(-3.52g[95%CI-7.04至0.01;z=1.96;P=0.05)]和LVEF[+2.54mL(95%CI1.10至3.98;z=3.62;P=0.0005)]。GLS(n=327)[+0.42%(95CI-0.19至1.02;P=0.18)]或LAVi[-3.25ml(95%CI-8.20至1.69;z=1.29;P=0.20)]无显著差异。
结论:这项荟萃分析提供了更多的数据和深入了解SGLT2抑制对心力衰竭患者心脏逆转重建的影响。与安慰剂对照相比,我们发现,SGLT2抑制剂治疗显著改善了逆转心脏重塑的几个标志物.
BACKGROUND: Several landmark randomized-controlled trials (RCTs) have demonstrated the efficacy of sodium-glucose co-transport 2 (SGLT2) inhibitors in reducing all-cause mortality, cardiovascular (CV) mortality and heart failure (HF) hospitalizations. Much interest surrounds their mechanism of action and whether they have direct effects on reverse cardiac
remodelling. Therefore, we conducted a meta-analysis of placebo controlled RCTs evaluating the impact of SGLT2 inhibition on imaging derived markers of reverse cardiac
remodelling in patients with HF.
METHODS: We performed a systematic review and meta-analysis in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) Statement and Cochrane Collaboration. Data interrogation of each major database including PubMed, EMBASE, MEDLINE and Cochrane Library was performed. RCTs evaluating HF patients >18 years comparing SGLT2 inhibitor versus placebo-control were included. Outcome measures included left ventricular end-diastolic volume and volume index (LVEDV/LVEDVi), left ventricular end-systolic volume and volume index (LVSDV/LVSDVi), left ventricular ejection fraction (LVEF), left ventricular mass index (LVMi), left atrial volume index (LAVi) and left ventricular global longitudinal strain (LV GLS). Studies with an HF with preserved ejection fraction population were excluded from analysis of parameters, which would be significantly affected by baseline LVEF, such as volumes and LVEF. The mean difference and standard error were extracted from each study and a random effects model used pool the mean difference and standard error across studies. A pre-specified sub-group analysis was performed to stratify results according to imaging modality used (cardiac magnetic resonance imaging and echocardiography). This study is registered on PROSPERO: CRD42023482722.
RESULTS: Seven randomized, placebo-controlled trials in patients with HF comprising a total population of 657 patients were included. Overall LVEF of included studies ranged from 29 ± 8.0% to 55.5 ± 4.2%. In studies included in analysis of HFrEF parameters, baseline LVEF ranged from 29 ± 8% to 45.5 ± 12%. Pooled data demonstrated SGLT2 inhibition, compared with placebo control, resulted in significant improvements in mean difference of LVEDV [-11.62 ml (95% confidence interval, CI -17.90 to -5.25; z = 3.67, P = 0.0004)], LVEDVi [-6.08 ml (95% CI -9.96 to -2.20; z = 3.07; P = 0.002)], LVESV [-12.47 ml (95% CI -19.12 to -5.82; z = 3.68; P = 0.0002)], LVESVi [-6.02 ml (95% CI -10.34 to -1.70; z = 2.73; P = 0.006)], LVM [-9.77 g (95% CI -17.65 to -1.89; z = 2.43; P = 0.02)], LVMi (-3.52 g [95% CI -7.04 to 0.01; z = 1.96; P = 0.05)] and LVEF [+2.54 mL (95% CI 1.10 to 3.98; z = 3.62; P = 0.0005)]. No significant difference in GLS (n = 327) [+0.42% (95%CI -0.19 to 1.02; P = 0.18)] or LAVi [-3.25 ml (95% CI -8.20 to 1.69; z = 1.29; P = 0.20)] was noted.
CONCLUSIONS: This meta-analysis provides additional data and insight into the effects of SGLT2 inhibition on reverse cardiac
remodelling in patients with HF. Compared with placebo control, we found that treatment with a SGLT2 inhibitor produced significant improvements in several markers of reverse cardiac
remodelling.