Immediate Versus Delayed Stenting in Patients with Acute ST-Elevation Myocardial Infarction: A Randomized Open-Label Bayesian Trial

Background: Stents immediately implanted in thrombus-laden arteries cause embolization, which paradoxically impairs myocardial reperfusion and function.   Methods: We conducted a Bayesian open-label randomized trial across 15 centres in France and Canada. Patients with acute ST-elevation myocardial infarction (STEMI) and reperfused by thrombectomy or small-size balloon angioplasty were randomly assigned to immediate stenting or to a bridging anti-thrombin therapy and delayed stenting between 18h to 48h after reperfusion. Using a hierarchical Bayesian analysis, we borrowed data from exchangeable twin trials to form a posterior probability of the risk ratio (RR) for the combined occurrence of cardiovascular death, heart failure, non-fatal myocardial infarction (MI), or target-vessel revascularisation (TVR) over 9 months in the intent-to-treat populations.   Findings: Between April 2014 and September 2017, 305 participants were randomly assigned to delayed (n = 152) or immediate stenting (n = 153). In parallel, four similar RCTs were reported that satisfied exchangeability requirements, leading to 1,873 participants, including 930 assigned to delayed and 943 assigned to immediate stenting. The primary endpoint occurred in 167 participants (18.1%) assigned to delayed stenting compared to 194 participants (20.6%) assigned to immediate stenting (RR, 0.91; 95% credible interval [95%CrI], 0.76 to 1.09; probability of superiority, 89%). Delayed stenting led to a meaningful increase in unplanned target revascularization acutely (RR, 1.54; 95% CrI, 0.98 to 2.41, probability of inferiority, 99%). At long term, delayed stenting reduced the combined occurrence of CV death or heart failure (RR, 0.83; 95% CrI, 0.67 to 1.02, probability of superiority, 99%).  Interpretation: In patients with STEMI, delayed stenting did not reduce the occurrence of cardiovascular death, non-fatal MI, heart failure and unplanned TVR compared to the immediate stenting. There is a high probability that delayed stenting substantially reduces cardiovascular death and heart failure in the longer-term. Trial Registration: ClinicalTrials.gov identifier: NCT01542385. Funding Statement: The trial was supported by an operating grant from the peer-reviewed, publically funded Canadian Institute of Health Research (CIHR), through the Industry-Partnered Collaborative Research program (grant #298937), in collaboration with Boston Scientific and AstraZeneca (unrestricted grants support). The industry partners played no role in the conduct and oversight of the study. Declaration of Interests: The investigators disclose the following relationships: E. Marc Jolicoeur: Advisory Board: Institut National d’Excellence en Sante et Services Sociaux du Quebec, Servier, Imbria Pharmaceutical, Carre technology; Board of Directors, Societe de Sciences Vasculaires du Quebec; Data Safety Monitoring Board: XyloCor; Research grants; Boston Scientific, AstraZeneca; The University of Glasgow (employer, C Berry) holds research and/or consultancy agreements with AstraZeneca, Abbott Vascular, Boehringer Ingelheim, GSK, HeartFlow, Novartis and Siemens Healthcare; Francois Roubille: Advisory Board: Abbott, Air liquide, Research grants; Boston Scientific, AstraZeneca. Consultancy agreements with AstraZeneca, Abbott Vascular, Air liquide, Amgen, Boehringer Ingelheim, GSK, MSD, Novartis, Sanofi, Novartis, Novonordisk, Vifor; Geraud Souteyrand: Consultancy agreements; Medtronic, Abbott, and Terumo; Guillaume Cayla: Consultancy agreements; Astra Zeneca, Amgen, Abbot Vascular, BMS, Boston, Biotronik, Medtronic, Pfizer, and Sanofi; Nicolas Delarche: Advisory board: Novartis; Samer Mansour: Consultant/Advisory board/Speaker’s Bureau: Abbott vascular, Soundbite, Boehringer Ingelheim, AstraZeneca, Bayer, BMS-Pfizer Alliance, Medtronic, Amgen, Sanofi, Servier, Gilead and Novartis; Erick Schampaert: Consultant/Advisory board/Speaker’s Bureau: Abbott, AstraZeneca, Bayer, BMS-Pfizer Alliance, Medtronic, Philips-Volcano, Servier; Loic Belle: Research Grant: AstraZeneca, Medtronic, Biotronic, Boston Scientific, Abbott Vascular, Terumo Ethics Approval Statement: The protocol complied with the Declaration of Helsinki and was approved by IRB at each participating centers. The trial was coordinated by the Montreal Health Innovation Coordinating Centre under the direction of the executive committee, which was responsible for trial conduct, the integrity of the data analysis, and the reporting of results.