SGLT2 INHIBITION FOR CARDIOVASCULAR ENDPOINT REDUCTION IN HYPERTENSION (SGLT2-HYPE)

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 reduce BP and might also improve outcomes for HTN by reducing end-organ damage through diverse 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; a key secondary endpoint assesses quality of life.

With 5,792 participants, assuming an annual placebo event rate of 2.5% compared to 2% with SGLT2i, a 3-year recruitment period and a minimum follow-up period of 4-years (7-years in total), the trial has 80% power for p<0.05 (two-sided).

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.