FX06, a fibrin-derived peptide, may reduce myocardial necrosis that is associated with successfully reperfused acute ST-segment elevation myocardial infarction (STEMI), according to results from the FX06 In Reperfusion (FIRE) trial. The FIRE trial showed only modest trends in favor of FX06 but suggests possible protection from reperfusion injury.

FX06 employs a novel mechanism for targeting acute inflammation, a common response to myocardial reperfusion and a possible cause of reperfusion injury. By inhibiting the binding of fibrin to cadherin, FX06 increases the vascular endothelium barrier function and obstructs the migration of leukocytes, thereby creating a blockage in the inflammatory cascade.

The exploratory phase 2 FIRE trial (NCT00326976) was designed to evaluate whether FX06 limits infarct size following primary percutaneous coronary intervention (PCI) for acute STEMI. Within 6 hours of the onset of STEMI symptoms, 234 patients were randomly assigned to receive intravenous FX06 400 mg (n=114) or placebo (n=120) at the time of reperfusion. The extent of muscle damage that was induced by reperfusion was assessed by cardiac magnetic resonance imaging (MRI).

Dan Atar, MD, Aker University Hospital, University of Oslo, Oslo, Norway, reported findings from the FIRE trial. When assessing myocardial damage, Prof. Atar and colleagues focused on the total infarct zone. This region contains the necrotic core zone (the infarct itself), the microvascular obstruction zone that is embedded within the necrosis, and an area of edema that surrounds the infarct. The primary endpoint was total infarct size 5 days after PCI, evaluated as the late enhancement zone.

Data from FIRE favored FX06, but the trial failed to meet its primary endpoint. While FX06 reduced the total infarct size by 21%, this difference between the FX06 and placebo groups was not statistically significant (21.68 g vs 27.34 g; p=0.21). However, FX06 significantly reduced the necrotic core zone by 58% compared with placebo (1.77 g vs 4.2 g; p=0.019, ie, the true infarction).

Although following PCI, FX06 also reduced the levels of cardiac necrosis biomarkers relative to placebo, including troponin I at 24 hours (−10%) and 48 hours (−17%) and CK-MB at 90 minutes (−16%), the decrease in biomarker release between treatment groups was not statistically significant.

The short-term benefits of FX06 did not appear to be maintained. At 4 months, there were no longer any significant differences between FX06 and placebo in total infarct size (15.37 g vs 19.32 g; p=0.36) or scar mass (1.79 g vs 2.84 g; p=0.16). This finding could be explained by shrinking of the scar. Left ventricular ejection fraction also was similar in the FX06 and placebo groups at Day 5 (46.7% vs 46.6%) and at 4 months (49.1% vs 48.9%).

FX06 did not increase the rate of serious adverse events (SAEs) compared with placebo. A similar number of patients in the FX06 and placebo groups suffered from cardiac death (2 vs 5), cardiac SAEs (21 vs 29), and the composite of cardiac death and new-onset heart failure or pulmonary edema (5 vs 10). Moreover, there was no evidence of altered cardiac rhythms, hypotension, or thrombotic risk that was associated with FX06.

Based on these initial findings, Prof. Atar believes that FX06 may have a role as a cardioprotective adjunct to PCI, although any positive trends need to be explored in a larger trial and he suggests that future trials focus on the outcomes of cardiac death and new-onset heart failure, which are known complications of STEMI.