In Vivo Studies of Coronary Stent Thrombosis in Model Systems and in Man

Introduction: Coronary stent thrombosis (ST) is a significant complication of percutaneous coronary intervention (PCI) associated with poor clinical outcomes. The aim of this thesis was to investigate the underlying causes and mechanisms of ST and to study the potential use of novel coronary stents. Methods: ST patients and controls were recruited to the PRESTIGE study and underwent detailed clinical assessment, optical coherence tomography (OCT), platelet function testing (PFT) and thrombin generation studies. A rabbit iliac model was developed to investigate the bio-neutrality of RGD-peptide stents and the thrombogenicity of Absorb bioabsorbable vascular scaffolds (BVS). Results: ST patients in the PRESTIGE study were younger, had more diabetes mellitus, thromboembolic antecedents, recent non-cardiac surgery, first generation drug eluting stents (DES), less aspirin use and less circumflex arteries involved. The OCT studies showed predominantly malapposition and under-expansion in early ST and uncovered struts and neoatherosclerosis in very late ST. Clopidogrel ‘high on treatment platelet reactivity’ (HPR) rates were high. The in vivo studies demonstrated more platelet adherence to the BVS than standard DES. The recovery model showed good healing and endothelialisation of RGD stents, with no ST at 28-days. However, this positive outcome was similar in the control bare metal stents (BMS). Conclusion: ST patients have risk factors that can potentially be used to predict risk in patients undergoing PCI. The rate of malapposition and under-expansion seen on OCT in early ST highlights the importance of adequate stent sizing and post dilation. The rate of uncovered struts and neoatherosclerosis in very late ST highlights the need for a more bio-neutral stent and aggressive secondary prevention. The in vivo results may partly explain some of the disappointing outcomes reported in the ABSORB II and III studies. Finally, the HPR rate on clopidogrel warrants further consideration when deciding on DAPT strategy in high risk patients.