Dapagliflozin Effect on Cardiovascular Outcomes in Haemodialysis for End Stage Renal Disease
Dapagliflozin Effect on Cardiovascular Outcomes in Haemodialysis for End Stage Renal Disease
This study aims to study SGLT2 inhibitors in patients who are undergoing haemodialysis for
 end stage renal disease and established ASCVD, to examine the safety and clinical outcomes,
 consisting of a composite of non-fatal stroke, non-fatal myocardial infarction, or
 cardiovascular death as the primary outcome. The key secondary composite outcome was all
 cause death or hospitalization for unstable angina.
Cardiovascular disease accounts for more than 50% of end-stage renal disease (ESRD) deaths.
 The reported cardiovascular death rates in patients receiving dialysis are substantially
 higher than in the general population. Cardiovascular mortality in ESRD is particularly high
 after acute myocardial infarction, but it is also elevated in ESRD patients with other forms
 of atherosclerotic vascular disease (eg, chronic coronary artery disease, strokes, transient
 ischemic attacks, and peripheral arterial disease). Left ventricular hypertrophy and dilation
 are associated with increased cardiovascular mortality, as is congestive heart failure. One
 of the major reasons for such high cardiovascular mortality in ESRD is the large burden of
 cardiovascular disease present in patients with chronic artery disease before renal
 replacement therapy.

 SGLT2 inhibitors have demonstrated benefits in reduction of major adverse cardiac events and
 heart failure hospitalisation in phase 3 randomised controlled trials. In addition, several
 recent clinical publications have also indicated renal benefits in patients with chronic
 renal impairment (eGFR >30ml/min).

 The primary SGLT2 inhibition predominantly occurs at the proximal tubules of kidneys. The
 mechanistic benefits postulated (other than serum glucose lowering) included SGL2i mediated
 naturesis and glucosuria. Independent of this class's effects at the renal level, SGL2i
 possibly affect cardiac metabolism (in animal studies), with reverse adverse cardiac
 remodelling by switching myocardial substrate utilization from glucose toward oxidation of
 fatty acids, ketone bodies and branch-chained amino acids. Such improvement in cardiac
 metabolism may attenuate myocardial ischemia, improve cardiac haemodynamics and reduce
 overall cardiac mortality, either independent of or synergistic with SGLT2 inhibition at the
 kidney level.

 Currently, there is a gap in knowledge and paucity of safety, efficacy and clinical outcomes
 data for the use of SGLT2 inhibitors in patients who are undergoing haemodialysis for end
 stage renal disease and established ASCVD.

 This study aims to study SGLT2 inhibitors in this population and examine the safety and
 clinical outcomes, consisting of a composite of non-fatal stroke, non-fatal myocardial
 infarction, or cardiovascular death as the primary outcome. The key secondary composite
 outcome was all cause death or hospitalization for unstable angina.
Inclusion Criteria:

 -  Provision of informed consent prior to any study specific procedures.

 -  Female or male aged ≥ 21 years.

 -  Undergoing haemodialysis for end stage renal disease regardless of cause and previous
 cardiac events.

 Exclusion Criteria:

 -  Diagnosis of Type 1 diabetes mellitus.

 -  Pregnant or planning pregnancy or breast-feeding patients.

 -  Any clinical condition that would jeopardize patient safety while participating in
 this clinical trial.

 -  Intake of an investigational drug or participating in another clinical trial involving
 an investigational drug.

 -  Life limiting disease other than ESRD with life expectancy estimated to be less than
 12 month.