Continuation vs Discontinuation of Dapagliflozin (SGLT‑2 inhibitor) in Heart Failure Patients Undergoing Cardiac Surgery: 30‑Day Cardiovascular Outcomes (DISCO Study)

The primary objective is to assess whether continuing SGLT-2 inhibitors up to the morning of cardiac surgery provides superior 30‑day cardiovascular outcome compared with discontinuation three days before surgery in patients with heart failure and reduced ejection fraction who have been on therapy for at least four weeks. Demonstrating a benefit would inform peri‑operative management and potentially reduce postoperative morbidity in this high‑risk population.

Secondary objectives include evaluation of the impact of the same pre‑operative strategy on:

• the incidence of perioperative myocardial injury at 2 days;
• the occurrence of low cardiac output syndrome at 7 days;
• the rate of rehospitalization for cardiac decompensation at day 30;
• the incidence of all‑cause mortality at 7 and 30 days;
• the frequency of euglycemic ketoacidosis within 7 days post‑operatively;
• the development of acute renal failure in intensive care within 7 days;
• the time to resume SGLT-2 inhibitor therapy after surgery;
• patient‑reported quality of life at 30 days;
• the duration of intensive care length of stay;
• the overall hospital stay.

The trial enrolled adult patients of both sexes who were scheduled for elective cardiac surgery requiring cardiopulmonary bypass. All participants had been receiving an SGLT‑2 inhibitor, with or without metformin, for a minimum of four weeks and demonstrated a left ventricular ejection fraction below 50% consistent with heart failure. Inclusion required signed informed consent and enrollment in a social security or equivalent scheme. The sponsor did not provide the total number of participants or specific age range details; therefore, the exact size of the study population and precise age limits are not disclosed. Lifestyle factors such as diet, physical activity, or other habits were not reported as selection criteria.

The DISCO Study is a phase IV, multicenter, randomized, double‑blind, controlled trial evaluating the impact of peri‑operative management of SGLT‑2 inhibitors on postoperative cardiovascular outcomes in adults with heart failure (left ventricular ejection fraction < 50%) scheduled for cardiac surgery with cardiopulmonary bypass. Eligible participants must have received dapagliflozin or empagliflozin, with or without metformin, for at least four weeks and provide informed consent. After a screening visit to confirm inclusion criteria and baseline assessments, participants are randomly assigned to either continue their SGLT‑2 inhibitor until the morning of surgery or discontinue the drug three days before surgery; both groups receive identical‑appearing tablets to maintain blinding. Study visits occur pre‑operatively (screening and randomization), intra‑operatively (recording of surgical details), and post‑operatively on day 1, day 2, day 7, and day 30 to collect high‑sensitivity troponin I levels, cardiac output data, rehospitalisation status, mortality, renal function, ketoacidosis, and quality‑of‑life questionnaires. The primary composite endpoint comprises peri‑operative myocardial injury, low cardiac output syndrome, 30‑day rehospitalisation for left‑sided heart failure, and all‑cause mortality at 30 days. Secondary endpoints assess each component individually, acute renal failure, euglycaemic ketoacidosis, time to resumption of SGLT‑2 inhibitor therapy, intensive‑care and total hospital length of stay, and EQ‑5D scores. Participant involvement extends from the screening visit through the day‑30 follow‑up, approximately 6–8 weeks. Early termination may occur if a participant withdraws consent, experiences a serious adverse event related to study medication, or violates major protocol criteria; investigators may also discontinue a participant for safety concerns. Recruitment commenced 1 May 2026 and is planned to conclude 1 September 2028.

The investigational product identified as dapagliflozin is supplied in oral tablet form (pharmaceutical identifier PHF00082MIG) at a strength of 10 mg per tablet. Administration follows the study protocol, with dosing recorded in the case report form.

The investigational product identified as empagliflozin is supplied in oral tablet form (pharmaceutical identifier PHF00082MIG) at a strength of 25 mg per tablet. Administration follows the study protocol, with dosing recorded in the case report form.

The combination product containing metformin hydrochloride and dapagliflozin is supplied in oral tablet form (pharmaceutical identifier PHF00082MIG) with a total tablet strength of 10 mg. The tablet provides both active substances and is administered orally as specified in the protocol.

The combination product containing metformin hydrochloride and empagliflozin is supplied in oral tablet form (pharmaceutical identifier PHF00082MIG) with a total tablet strength of 25 mg. The tablet provides both active substances and is administered orally as specified in the protocol.

Participants allocated to the control arm discontinue the SGLT-2 inhibitor regimen three days prior to the scheduled cardiac operation, thereby receiving no study medication during the peri‑operative period. This approach reflects standard‑of‑care management for patients not continuing SGLT‑2 inhibition.

Subjects randomized to continue therapy receive the assigned oral tablet on the morning of surgery, which involves cardiopulmonary bypass. Drug intake is documented in the case report form, and adherence is verified by study personnel at each peri‑operative assessment.

The efficacy assessment will focus on a composite primary endpoint comprising peri‑operative myocardial injury, low cardiac output syndrome, rehospitalisation for left‑sided heart failure, and all‑cause mortality within 30 days after surgery. Myocardial injury is identified by an increase in high‑sensitivity troponin I measured during the first 48 hours post‑operatively, using laboratory‑specific threshold multiples (218× for coronary artery bypass grafting or aortic valve procedures, 499× for other cardiac surgeries). Low cardiac output syndrome is recorded when positive inotropes are required for more than 48 hours or when temporary mechanical circulatory support (ECLS, CPIA, Impella®) is initiated within the first 7 days. Rehospitalisation for left heart failure is captured if, within 30 days, patients require escalation of diuretics, inotropes, or ventilatory support for acute pulmonary oedema, with stays limited to cardiology‑related units. All‑cause mortality is documented at both 7 days and 30 days post‑surgery. Data collection follows predefined timepoints: biomarker sampling at 0–48 hours, clinical monitoring for cardiac output and support devices up to day 7, and follow‑up visits or record reviews at days 7 and 30 for rehospitalisation and mortality outcomes.

Secondary efficacy parameters include the individual components of the primary composite, as well as euglycaemic ketoacidosis (pH < 7.35, capillary ketonemia > 0.6 mmol/L, glucose < 2.5 g/L within 7 days), acute renal failure (KDIGO stage ≥ 2 in intensive care within 7 days), the interval in days before postoperative resumption of SGLT‑2 inhibitors, health‑related quality of life assessed with the EQ5D questionnaire performed the day before surgery and on day 30, intensive‑care unit length of stay, and total hospital length of stay. Each secondary endpoint will be measured according to its specified definition and recorded at the corresponding postoperative interval, with laboratory assays, clinical observations, and patient‑reported outcomes processed using standard statistical methods for comparative analysis between the continuation and discontinuation groups.