Meta-Analysis of Cell-based CaRdiac stUdiEs (ACCRUE) in patients with acute myocardial infarction based on individual patient data

Mariann Gyöngyösi, Wojciech Wojakowski, Patricia Lemarchand, Ketil Lunde, Michal Tendera, Jozef Bartunek, Eduardo Marban, Birgit Assmus, Timothy D Henry, Jay H Traverse, Lemuel A Moyé, Daniel Sürder, Roberto Corti, Heikki Huikuri, Johanna Miettinen, Jochen Wöhrle, Slobodan Obradovic, Jérome Roncalli, Konstantinos Malliaras, Evgeny Pokushalov, Alexander Romanov, Jens Kastrup, Martin W Bergmann, Douwe E Atsma, Axel Diederichsen, Istvan Edes, Imre Benedek, Theodora Benedek, Hristo Pejkov, Noemi Nyolczas, Noemi Pavo, Jutta Bergler-Klein, Imre J Pavo, Christer Sylven, Sergio Berti, Eliano P Navarese, Gerald Maurer, ACCRUE Investigators, Rayyan Hemetsberger, Dietmar Glogar, Sasko Kedev, Erik Jørgensen, Yongzhong Wang, Rasmus S Ripa, Mariann Gyöngyösi, Wojciech Wojakowski, Patricia Lemarchand, Ketil Lunde, Michal Tendera, Jozef Bartunek, Eduardo Marban, Birgit Assmus, Timothy D Henry, Jay H Traverse, Lemuel A Moyé, Daniel Sürder, Roberto Corti, Heikki Huikuri, Johanna Miettinen, Jochen Wöhrle, Slobodan Obradovic, Jérome Roncalli, Konstantinos Malliaras, Evgeny Pokushalov, Alexander Romanov, Jens Kastrup, Martin W Bergmann, Douwe E Atsma, Axel Diederichsen, Istvan Edes, Imre Benedek, Theodora Benedek, Hristo Pejkov, Noemi Nyolczas, Noemi Pavo, Jutta Bergler-Klein, Imre J Pavo, Christer Sylven, Sergio Berti, Eliano P Navarese, Gerald Maurer, ACCRUE Investigators, Rayyan Hemetsberger, Dietmar Glogar, Sasko Kedev, Erik Jørgensen, Yongzhong Wang, Rasmus S Ripa

Abstract

Rationale: The meta-Analysis of Cell-based CaRdiac study is the first prospectively declared collaborative multinational database, including individual data of patients with ischemic heart disease treated with cell therapy.

Objective: We analyzed the safety and efficacy of intracoronary cell therapy after acute myocardial infarction (AMI), including individual patient data from 12 randomized trials (ASTAMI, Aalst, BOOST, BONAMI, CADUCEUS, FINCELL, REGENT, REPAIR-AMI, SCAMI, SWISS-AMI, TIME, LATE-TIME; n=1252).

Methods and results: The primary end point was freedom from combined major adverse cardiac and cerebrovascular events (including all-cause death, AMI recurrance, stroke, and target vessel revascularization). The secondary end point was freedom from hard clinical end points (death, AMI recurrence, or stroke), assessed with random-effects meta-analyses and Cox regressions for interactions. Secondary efficacy end points included changes in end-diastolic volume, end-systolic volume, and ejection fraction, analyzed with random-effects meta-analyses and ANCOVA. We reported weighted mean differences between cell therapy and control groups. No effect of cell therapy on major adverse cardiac and cerebrovascular events (14.0% versus 16.3%; hazard ratio, 0.86; 95% confidence interval, 0.63-1.18) or death (1.4% versus 2.1%) or death/AMI recurrence/stroke (2.9% versus 4.7%) was identified in comparison with controls. No changes in ejection fraction (mean difference: 0.96%; 95% confidence interval, -0.2 to 2.1), end-diastolic volume, or systolic volume were observed compared with controls. These results were not influenced by anterior AMI location, reduced baseline ejection fraction, or the use of MRI for assessing left ventricular parameters.

Conclusions: This meta-analysis of individual patient data from randomized trials in patients with recent AMI revealed that intracoronary cell therapy provided no benefit, in terms of clinical events or changes in left ventricular function.

Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01098591.

Keywords: anterior wall myocardial infarction; heart failure; meta-analysis; outcome assessment; stem cells.