American Heart Journal Plus (Jun 2022)
Preventative effects of dapagliflozin on early ventricular dysfunction and remodeling in patients with acute anterior STEMI - The PREDOMINACE trial
Abstract
Background: Sodium glucose cotransporter 2 inhibitors (SGLT-2i) are oral hypoglycemic drugs that can reduce the risk of deteriorating heart failure (HF) or cardiovascular death in patients with HF. Although some animal models have shown that SGLT-2i can effectively inhibit reperfusion injury after acute myocardial infarction (AMI), there is no clinical evidence to prove that SGLT-2i can also play a significant role in improving reperfusion injury in patients with AMI. Therefore, PREDOMINACE study enrolled patients with acute anterior large ST-segment elevation myocardial infarction, who are at high risk of developing HF in the future. The aim of this trial is to study the prevention effects of dapagliflozin on early ventricular dysfunction and remodeling in patients with acute anterior ST-segment elevation myocardial infarction (STEMI), and to explore the efficacy and safety of dapagliflozin in the treatment of patients with diabetes and without diabetes after acute anterior STEMI. Methods: Within a multi-center, randomized, single-blind, controlled trial we will recruit patients with acute anterior STEMI from the Second Hospital of Tianjin Medical University and Tianjin Chest Hospital, who are randomly divided into intervention group or control group in a 1:1 ratio. The intervention group was given dapagliflozin (10 mg once daily) before primary percutaneous coronary intervention (PPCI) and 30 days after PPCI, while the control group is not given SGLT-2i. The primary endpoint is the impact of dapagliflozin on changes of NT-proBNP levels in 30 days of acute anterior STEMI. Secondary endpoints include changes in echocardiographic left ventricular remodeling parameters (LVESV, LVEDV, EF), and the changes of ECG (Q wave leads 30 days after PPCI/ST-segment elevation leads at baseline,ST-segment decline degree 24 h and 7 days after PPCI). Hospitalization rate due to HF or other causes, incidence of malignant arrhythmias, and all-cause mortality will be assessed as exploratory secondary endpoints. Discussion: The PREDOMINACE trial will test dapagliflozin in patients with acute anterior STEMI, regardless of the presence or absence of diabetes. Therefore, the PREDOMINACE trial may support that the effects of SGLT-2i on improving cardiac remodeling, reducing cardiac pre and after load and improving cardiac metabolism are independent of its antidiabetic effects. Results will provide the clinical rationale for SGLT-2i to improve prognosis in patients with AMI.Trial registration: Chinese Clinical Trial Registry. Identifier: ChiCTR2100048157. Registered 23 September 2021.
