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

• Applicant: Dr. Peter Moritz Becher
• Subject Area: Cardiology, Angiology
• Term: from 2021 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 456458270

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.

• DFG Programme: WBP Fellowship
• International Connection: Sweden
• Host: Professor Dr. Gianluigi Savarese