Use of the inhibitors of sodium-glucose cotransporter 2 in patients with different heart failure phenotypes and with type 2 diabetes mellitus

钠-葡萄糖协同转运蛋白2抑制剂在不同心力衰竭表型和2型糖尿病患者中的应用

• 批准号: 456458270
• 负责人: Dr. Peter Moritz Becher
• 金额: --
• 依托单位: Karolinska Institutet
• 依托单位国家: 德国
• 项目类别: WBP Fellowship
• 财政年份: 2021
• 资助国家: 德国
• 起止时间: 2020-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/456458270?language=en
• 关键词: Use; inhibitors; sodium; glucose; cotransporter

Heart failure (HF) is an important cardiovascular disease due to its increasing prevalence, significant morbidity, and still high mortality rates. HF is a complex clinical syndrome characterized by distinct symptoms, which is caused by structural and/ or functional cardiac abnormalities. Type 2 diabetes mellitus (T2DM) is a risk factor for incident HF and causes a considerable financial burden on health care systems in the western world. T2DM and HF often occur concomitantly and both diseases independently increase the risk for each other. In HF cohorts of patients with HFrEF and HFpEF, the prevalence of T2DM reports of 10% to 47%. Moreover, patients suffering from HF and concomitant T2DM showed impaired prognosis as compared with those patients suffering from only one of these chronic diseases. Given the important interaction between HF and T2DM, aggravation of HF has been used as a significant secondary endpoint in all the current randomized controlled trails (RCTs) focusing on T2DM treatments in HF patients. Inhibitors of sodium-glucose cotransporter 2 (SGLT2i) block the sodium-glucose transport protein 2 in the proximal convoluted tube of the kidney. In detail, SGLT2i increase the urinary glucose excretion, which improves glycemic control and natriuresis. These two mechanisms lead to a decreased extracellular volume, which may lead to a reduction in vascular wall stress, enhanced cardiac function and less congestion in decompensated HF patients. Hemodynamic, metabolic as well as renal effects induced by SGLT2i may be beneficial in patients with HF. The recent trials EMPA-REG OUTCOME and CANVAS showed that the treatment with the SGLT2i canagliflozin and empagliflozin compared to standard of care significantly reduced the risk of hospitalization and death in patients with T2DM. The DECLARE TIMI 58 trial revealed a 17% reduction of the risk of cardiovascular death or HF hospitalization with dapagliflozin.SGLT2i have recently been introduced to the market and have been poorly tested in real-world patients in terms of effectiveness, in particular in HF populations and their specific phenotypes. Although efficacy of treatments can only be assessed only by randomized controlled trials, patient populations in clinical trials are highly selected and thus analyses in large real-world populations are needed to assess generalizability of trials’ findings (i.e. effectiveness). Therefore, the aim of the proposed research project is to describe current use and outcomes associated with use of SGLT2i in one of the world-largest and prospective cohort of T2DM patients with HF. Moreover, use and outcomes across the ejection fraction spectrum (HFpEF, HFmrEF, HFrEF) and subgroups of patients by age, sex and comorbidities will be investigated in SwedeHF registry.

心力衰竭（HF）是一种重要的心血管疾病，由于其患病率不断增加，发病率显著，死亡率仍然很高。HF是一种复杂的临床综合征，其特征在于独特的症状，其由心脏结构和/或功能异常引起。2型糖尿病（T2 DM）是HF事件的风险因素，并给西方国家的医疗保健系统造成相当大的经济负担。T2 DM和HF通常伴随发生，两种疾病独立地增加彼此的风险。在HFrEF和HFpEF患者的HF队列中，T2 DM的患病率报告为10%-47%。此外，与仅患有其中一种慢性疾病的患者相比，患有HF和伴随T2 DM的患者显示预后受损。鉴于HF和T2 DM之间的重要相互作用，HF加重已被用作当前所有关注HF患者T2 DM治疗的随机对照试验（RCT）的重要次要终点。钠-葡萄糖协同转运蛋白2（SGLT 2 i）抑制剂阻断肾脏近曲管中的钠-葡萄糖转运蛋白2。具体而言，SGLT 2 i可增加尿糖排泄，从而改善血糖控制和尿钠排泄。这两种机制导致细胞外容量减少，这可能导致失代偿性HF患者血管壁应力降低、心脏功能增强和充血减少。SGLT 2 i诱导的血流动力学、代谢和肾脏效应可能对HF患者有益。最近的试验EMPA-REG OUTCOME和CANVAS显示，与标准治疗相比，SGLT 2 i卡格列净和恩格列净治疗显著降低了T2 DM患者的住院和死亡风险。DAPAGLIFLOZIN.SGLT2i最近被引入市场，在现实世界的患者中，特别是在HF人群及其特定表型中，其有效性的测试结果很差。虽然治疗的有效性只能通过随机对照试验进行评估，但临床试验中的患者人群是高度选择性的，因此需要在大型现实人群中进行分析，以评估试验结果的普遍性（即有效性）。因此，拟定研究项目的目的是描述SGLT 2 i在一个全球最大的T2 DM HF患者前瞻性队列中的当前使用情况和使用相关结局。此外，将在SwedeHF登记研究中研究射血分数谱（HFpEF、HFmrEF、HFrEF）和按年龄、性别和合并症划分的患者亚组的使用和结局。