Prospective validation of the ARC HBR trade off model in the all comer PIONEER IV trial
Authors: Tsai T , Wykrzykowska J , Rosseel L , Sharif F , Alkhalil M , Benit E , De Wilder K , Baumbach A , Smits P , Nash P , Onuma Y , Serruys P 
Published: October 2024

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