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EXPEDITED PUBLICATION

Effect of Intravenous FX06 as an Adjunct to Primary Percutaneous Coronary Intervention for Acute ST-Segment Elevation Myocardial Infarction

Results of the F.I.R.E. (Efficacy of FX06 in the Prevention of Myocardial Reperfusion Injury) Trial

Dan Atar, MD, PhD, FACC^_*,_*, Peter Petzelbauer, MD, PhD, Jürg Schwitter, MD, Kurt Huber, MD, FACC, Benno Rensing, MD^||, Jaroslaw D. Kasprzak, MD, PhD^¶, Christian Butter, MD^#, Lars Grip, MD, PhD^_**, Peter R. Hansen, MD, PhD, Tim Süselbeck, MD, Peter R. Clemmensen, MD, PhD, Marcos Marin-Galiano, PhD^||||, Bernard Geudelin, MD^¶¶, Peter T. Buser, MD, FACC^## F.I.R.E. Investigators

^_* Division of Cardiology and Faculty of Medicine, Aker University Hospital, University of Oslo, Oslo, Norway
Medical University of Vienna, Vienna, Austria
Department of Cardiology, Zurich University Hospital, Zurich, Switzerland
Department of Cardiology and Emergency Medicine, Wilhelminenhospital, Vienna, Austria
^|| Department of Cardiology, St. Antonius Ziekenhuis, Nieuwegein, the Netherlands
^¶ Szpital im. Bieganskiego, II Chair of Cardiology, Medical University of Lódz, Lódz, Poland
^# Heart Center Brandenburg in Bernau-Cardiology, Brandenburg, Germany
^_** Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden
Copenhagen University Hospital Gentofte, Hellerup, Denmark
Universitätsklinikum Mannheim I. Medizinische Klinik/Kardiologie, Mannheim, Germany
Rigshospitalet, Copenhagen University Hospital, Blegdamsvej, Copenhagen, Denmark
^|||| IFE Europe GmbH, Essen, Germany
^¶¶ Fibrex Medical Research and Development GmbH, Vienna, Austria
^## University Hospital Basel, Department of Cardiology, Basel, Switzerland

Manuscript received August 8, 2008; revised manuscript received December 15, 2008, accepted December 16, 2008.

^_* Reprint requests and correspondence: Dr. Dan Atar, Professor and Head of Cardiology, Aker University Hospital, University of Oslo, N-0514 Oslo, Norway (Email: dan.atar{at}online.no).

Objectives: The purpose of this study was to investigate whether FX06 would limit infarct size when given as an adjunct to percutaneous coronary intervention.

Background: FX06, a naturally occurring peptide derived from human fibrin, has been shown to reduce myocardial infarct size in animal models by mitigating reperfusion injury.

Methods: In all, 234 patients presenting with acute ST-segment elevation myocardial infarction were randomized in 26 centers. FX06 or matching placebo was given as intravenous bolus at reperfusion. Infarct size was assessed 5 days after myocardial infarction by late gadolinium enhanced cardiac magnetic resonance imaging. Secondary outcomes included size of necrotic core zone and microvascular obstruction at 5 days, infarct size at 4 months, left ventricular function, troponin I levels, and safety.

Results: There were no baseline differences between groups. On day 5, there was no significant difference in total late gadolinium enhanced zone in the FX06 group compared with placebo (reduction by 21%; p = 0.207). The necrotic core zone, however, was significantly reduced by 58% (median 1.77 g [interquartile range 0.0, 9.09 g] vs. 4.20 g [interquartile range 0.3, 9.93 g]; p < 0.025). There were no significant differences in troponin I levels (at 48 h, –17% in the FX06 group). After 4 months, there were no longer significant differences in scar size. There were numerically fewer serious cardiac events in the FX06-treated group, and no differences in adverse events.

Conclusions: In this proof-of-concept trial, FX06 reduced the necrotic core zone as one measure of infarct size on magnetic resonance imaging, while total late enhancement was not significantly different between groups. The drug appears safe and well tolerated. (Efficacy of FX06 in the Prevention of Myocardial Reperfusion Injury [F.I.R.E.]; NCT00326976 [ClinicalTrials.gov] )

Key Words: acute myocardial infarction • ST-segment elevation • percutaneous coronary intervention • reperfusion injury • FX06 • cardiac magnetic resonance imaging

Abbreviations and Acronyms   ANCOVA = analysis of covariance   CMR = cardiac magnetic resonance imaging   ECG = electrocardiogram   IQR = interquartile range   LGE = late gadolinium enhanced   MVO = microvascular obstruction   PCI = percutaneous coronary intervention   STEMI = ST-segment elevation myocardial infarction

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