Project name: SGLT2-HYPE: Inhibition for cardiovascular endpoint reduction in hypertension 

Project start date: 1. 1. 2025
Project completion date: 30. 6. 2032
Project Budget: total EUR 6,699,998.95 (of which EUR 33,369.38 for VFN)
Project guarantor: 2nd Department of Internal Medicine, Prof. MUDr. Jan Bělohlávek, Ph.D.
Project Registration Number: 101156555

Project brief:

The project is supported by the EU Horizon EUROPE programme and will be implemented by an international consortium comprising 17 entities from 13 European countries. The project coordinator is the University Hospital Schleswig – Holstein, Germany; the VFN is one of the partners.

Hypertension is a major cause of cardiovascular disease (CVD), affecting more than 80 million EU citizens and more than 50% of people over 65 years of age, resulting in 1 million deaths per year, mainly from CVD and chronic kidney disease. Despite existing treatments, patients with hypertension are still at significant risk due to pre-existing and ongoing end-organ damage, partly caused by inadequate blood pressure control. SGLT2 inhibitors (SGLT2i) are recommended in both type 2 diabetes and heart failure to reduce morbidity and mortality. SGLT2i lower blood pressure and may also improve outcomes by reducing end-organ damage through various other effects. However, confirmation that SGLT2i are clinically useful for the treatment of hypertension is needed to change recommendations and clinical practice.

The aim of the project is to assess whether the addition of SGLT2i to standard antihypertensive therapy reduces the incidence of cardiovascular events. The project will conduct a multicenter, double-blind, randomized, placebo-controlled trial (SGLT2-HYPE) that will compare the effects of dapagliflozin with placebo in people with inadequately controlled HTN, aged ≥ 65 years and with at least one other cardiovascular disease or risk factor. The results of this study could initiate a paradigm shift towards the use of a new class of drugs in the primary treatment of hypertension.

The II. Department of Internal Medicine of the General Hospital in Prague will participate in the consortium in the inclusion of suitable patients in the project and the collection of biological samples (serum, plasma, urine) for molecular and proteomic analyses, which will contribute to the clarification of the basic biological processes affected by SGLT2i treatment in HTN. The collected samples will help to identify biomarkers and their influence on cardiovascular outcomes in HTN, progression of heart failure and cardiac remodeling. 

Abstract in English:

Hypertension (HTN) is a leading cause of cardiovascular disease (CVD), affecting >80 million EU citizens and >50% of people aged >65 years, resulting in 1 million deaths per year, predominantly from CVD and chronic kidney disease (CKD). The damage done by CVD costs almost €300 billion annually in the EU alone. Despite existing therapies, patients with HTN still face substantial risks, due to pre-existing and ongoing end-organ damage due, in part, to inadequate blood pressure (BP) control. SGLT2 inhibitors (SGLT2i) are recommended for both type-2 diabetes and heart failure to reduce morbidity and mortality. SGLT2i reduces BP and might also improve outcomes for HTN by reducing end-organ damage through various other actions. However, confirmation that SGLT2i are clinically useful for the management of HTN is required to change guidelines and clinical practice. Therefore, we designed a multicentre, double-blind, randomised, placebo-controlled trial (SGLT2-HYPE), comparing the effects of dapagliflozin to placebo in people with inadequately controlled HTN, aged ≥65 years and with at least one other CVD or risk factor. The primary endpoint is a composite of CVD and CKD morbidity and mortality; and key secondary endpoint assesses quality of life. This guideline-relevant trial will inform guidelines and practice and may introduce a new therapeutic class for HTN, enhancing the current standard of care for an extremely common, treatable cause of CVD/CKD to reduce or prevent morbidity, disability and death. By engaging with key stakeholders, the trial aims to not only revolutionize care and wellbeing but also to achieve substantial healthcare cost savings (~€10 billion annually across the EU) and prevent >250,000 deaths globally each year.

Links and other materials:

• Coordinator's press release to launch the project