Prospective validation of the ARC HBR trade off model in the all comer PIONEER IV trial

Abstract Introduction Bleeding and thrombotic events can impact patients’ survival after percutaneous coronary intervention (PCI). However, given these events often have common predictors, device selection and pharmacotherapy are a difficult conundrum. Urban et al.(1) developed the ARC–High Bleeding Risk(HBR) Trade-off Model to predict the bleeding and thrombosis risk in HBR patients. Purpose We aim to validate prospectively whether the HBR ARC formula can be applied to non-HBR patients treated with new-generation stents with rapid healing design. Methods We validated the ARC-HBR trade-off model in the ongoing all-comers PIONEER IV trial, a randomized controlled trial comparing PCI outcomes between angiography-derived physiology guidance or angiographic guidance approach, with the use of diagnostic tests at physician discretion. All PCIs were performed with the Healing-Targeted Supreme (HT Supreme) stents, a thin strut drug-eluting stent covered with a bio-degradable polymer coating that consists of an electro-grafted fracture/delamination-resistant base layer (150-200nm), interdigitated with a polyglycolic lactate layer that releases 90% of sirolimus within 30 days with a peak arterial concentration at 20 days. The coating minimizes excess neointimal proliferation while allowing rapid endothelialization. All patients received 1 month of dual antiplatelet therapy (DAPT), followed by 11 months of ticagrelor monotherapy. The clinical data were obtained from the trial database. Patients who passed 6-month follow-up were included. The study endpoints are: 1) myocardial infarction(MI) and/or stent thrombosis (ST) and 2)Bleeding Academic Research Consortium (BARC) types 3 to 5 bleeding. Results As of January 2024, 1270 patients were enrolled. A total of 638 passed 6 months follow-up. At 180 days, 12 patients (1.9%) had BARC types 3 to 5 bleeding, and 17 (2.7%) experienced an MI and/or ST (16 MIs [2.5%] and 2 [0.3%] STs). Using the formulas, the estimated risks of thrombosis and bleeding were 2.5% (IQR 1.8%-3.9%) and 2.1%(IQR 2.0%-3.4%), respectively, with the area under the receiver operation curve (ROC) of 0.64 (CI 0.48-0.80) for predicting BARC types 3 to 5 bleeding (Fig1A), and 0.56 (0.39-0.73) for predicting MI and/or ST(Fig1A). Among the 129 HBR patients, the estimated bleeding and thrombotic risks were 3.4% and 2.8%, respectively. The AUC of ROC is 0.66(CI 0.43-0.90) and 0.58(CI 0.04-1) for predicting bleeding(Fig2A) and thrombosis(Fig2B), respectively. At 180 days, 5 HBR patients (3.9%) had BARC types 3 to 5 bleeding, 3 (2.3%) experienced MI, but no patient experienced ST. Conclusion The ARC-HBR trade-off model modestly predicted the risk of bleeding and thrombosis in non-HBR patients treated with HT Supreme stents and 1-month DAPT. However, while the bleeding model could predict the risk of bleeding, the thrombosis model failed to differentiate patients at high risk of events.Figure 1Figure 2