Target trial emulation framework
death
In this study, we aimed to evaluate whether levosimendan administration in patients with VA-ECMO support shortened the time to successful ECMO weaning and reduced mortality at 30-day and at 1-year. We thus emulated a hypothetical target trial in which patients were randomly assigned to levosimendan administration or no levosimendan administration, and for which eligibility criteria, ECMO procedures (implantation and weaning), and outcomes would be the same for its emulation with observational data [The target trial was emulated from our cohort each time the comparison between the two arms of the target trial were possible during the duration of ECMO support, i.e., when there was at least one patient eligible to the study who received levosimendan. Patients were eligible multiple times during follow-up; thus, a copy of a patient was created each time a patient could participate to a nested emulated trial. Patients eligible at a given time point were alive, still receiving ECMO, and did not receive levosimendan at previous time points (new-users design). At baseline of each emulated trial, patients were classified as receiving levosimendan if they started levosimendan on the ECMO day or not receiving levosimendan otherwise, and potential confounding was measured. The day zero (first follow-up) was defined as the day of beginning of ECMO support. Patients (and their respective copies) were followed from baseline of each emulated trial until death or 1-year after ICU admission (end of data collection on December 31, 2020). This methodological strategy makes coincide the time of eligibility criteria assessment, treatment assignment and starting of follow-up, thus removing immortal-time bias related to the delay between ECMO initiation and levosimendan administration [Sequential emulation of the target trial. The target trial (as defined in Additional file 