Introduction: the role of beta blockers (BB) post-myocardial infarction (MI) in patients without reduced ejection fraction in the era of invasive management is controversial. Results from observational studies have led to opposite results.
Methods: REBOOT is an independent multinational pragmatic, controlled, randomized, open-label, with blinded endpoint adjudication clinical trial. The study is testing the benefits of BB maintenance therapy in post-MI patients (either with or without ST segment elevation) discharged with LVEF >40%. Patients ≥18 years old undergoing invasive management during admission and without history of heart failure (HF) are eligible to participate. At discharge, they are 1:1 randomized to either receive BB (agent and dose chosen by the treating physician) or no BB therapy. The primary endpoint is a composite of all-cause death, nonfatal re-MI, or heart failure hospitalization over a minimum follow-up period of 2.75 years (minimum 2 years, maximum 3 years). Events are adjudicated by a blinded committee. Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC) is the sponsor of the trial and the coordinator of Spanish Centers while Istituto di Ricerche Farmacologiche Mario Negri IRCCS coordinates the Italian participating network. Hospital admission for COVID-19 were also recorded since June 2020.
Results: the study is currently ongoing and 29 Italian centers are still actively recruiting. A sample size of 8468 pts (728 events) was estimated to provide a power of 85% to detect a RRR of 20% (incidence of primary endpoint in control 10%) and assuming 5% withdrawals. More than 75 Spanish and 35 Italian centers recruited patients. The first patients have been included in Spain in October 2018, in Italy in January 2019. On December 31st 2022, the number of enrolled patients by Italian centers was 1685. The top three Italian enrollers at the moment are: Ospedale G. da Saliceto -Piacenza (483 pts), Ospedale S. Luigi Gonzaga – Orbassano (183 pts) and A.O San’Anna and San Sebastiano – Caserta (170 pts). The patient enrollment rate was almost stable during all the study periods with a slight decrease during COVID pandemic outbreaks. The Italian REBOOT Network goal is to include 1800 patients by April 2023. The first results will become available by the end of 2025.
Conclusion: The REBOOT, with other ongoing trials, will provide robust evidence to guide the prescription of BB to patients discharged after MI without reduced LVEF.