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

心力衰竭(HF)是一种重要的心血管疾病，其发病率、发病率和死亡率仍居高不下。心力衰竭是一种复杂的临床综合征，具有明显的症状，由心脏结构和/或功能异常引起。2型糖尿病(T2 DM)是心力衰竭发病的危险因素，对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经常同时发生，两种疾病单独存在会增加彼此的风险。在HFrEF和HFpEF患者的HF队列中，T2 DM的患病率报告为10%到47%。此外，与仅患有其中一种慢性病的患者相比，患有心力衰竭并伴有T2 DM的患者预后不良。鉴于心力衰竭与2型糖尿病之间的重要相互作用，心力衰竭加重已被作为目前所有关注心力衰竭患者2型糖尿病治疗的随机对照试验(RCT)中的一个重要的次要终点。钠-葡萄糖共转运蛋白2的抑制剂(SGLT2i)阻断了肾脏近曲小管中的钠-葡萄糖转运蛋白2。更详细地说，SGLT2i可增加尿糖排泄，改善血糖控制和钠尿。这两种机制导致细胞外体积减少，这可能导致失代偿期心衰患者血管壁应力降低、心功能增强和充血减少。SGLT2i对心力衰竭患者的血流动力学、代谢和肾脏影响可能是有益的。最近的EMPA-REG试验结果和CAVAS显示，与标准治疗相比，使用SGLT2i卡那利福秦和埃帕利福秦的治疗显著降低了T2 DM患者的住院和死亡风险。CREATE TIMI 58试验显示，服用达帕利嗪可将心血管死亡或心力衰竭住院的风险降低17%。SGLT2i最近已被推向市场，但在现实世界的患者中的有效性测试很差，特别是在心力衰竭人群及其特定表型方面。虽然治疗的有效性只能通过随机对照试验来评估，但临床试验中的患者群体是高度选定的，因此需要在大量真实人群中进行分析，以评估试验结果的概括性(即有效性)。因此，建议的研究项目的目的是描述SGLT2i在世界上最大的和预期的T2 DM合并心力衰竭患者队列中的当前使用情况和与使用SGLT2i相关的结果。此外，射血分数谱(HFpEF、HFmrEF、HFrEF)以及按年龄、性别和合并症分组的患者的使用和结果将在SwedeHF登记中进行调查。

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.