Fractalkine Inhibition in Acute Myocardial Infarction leads to reduced intramyocardial haemorrhage

Abstract Background The fractalkine receptor CX3CR1 has been linked to the development of microvascular obstruction (MVO) in ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PPCI). Pre-clinical studies have demonstrated a reduction in infarct size, inflammation and intramyocardial haemorrhage (IMH) with inhibition of CX3CR1. Purpose The FRACTAL study is a phase IIa, pilot, randomized, 2-arm parallel group, placebo-controlled, double blinded, multi-centre trial. In addition to assessing the safety and tolerability of the fractalkine inhibitor KAND567 in STEMI patients, a subgroup exploratory analysis was performed. We investigated into the translation of MRI and blood samples characteristics between the two groups. Methods Patients with an anterior STEMI who had an occluded proximal to mid left anterior descending (LAD) artery were recruited. These patients had to present within 5 hours of the onset of their chest pain. They were subsequently randomised on a 1:1 basis to receive either KAND567 or placebo. Patients then underwent an MRI at day 3, and subsequently a comparator at 3 months. Additionally, throughout the period of their follow-up, patients would regularly undergo blood sampling to assess multiple parameters. Results Of the 71 patients recruited into the study, 29 patients in the KAND567 arm and 28 patients in the placebo arm received both MRIs. The KAND567 arm had shown a similar troponin rise at day 1 compared to placebo (4357 vs 4286). Baseline MRI demonstrated an identical infarct size between both arms. The presence and absence of IMH was then analysed defining IMH+ as presence of IMH and IMH- as IMH absence. The presence of IMH in patients showed a larger infarct size. The infarct size of IMH+ were the same between KAND567 and placebo, which was a similar finding in the IMH- arm too. However, when compared to day 90 MRI demonstrated a numerically smaller infarct size in the KAND567 group with a smaller percentage of IMH. This was consistent with a lower rate of IMH in the KAND567 arm too, when compared between the groups (35.5% vs 55.2%; p=0.15) (see table below). This seemed to be related to the smaller distribution IMH+, as the IMH+ infarcts were much larger in both arms, whilst overall infarct size in IMH subgroup were identical. Conclusion KAND567 appears to prevent the transition from IMH- to IMH+, while it doesn’t change infarct size in the respective subgroups of IMH+ or IMH-.MRI Comparator Table