Residual physiological profiles in patients with CABG- or PCI-Favored coronary anatomy: A post hoc analysis of the PANDA III randomized clinical trial

BACKGROUND AND AIMS Patients with anatomically complex coronary artery disease may be considered more suitable for coronary artery bypass grafting (CABG) than percutaneous coronary intervention (PCI), but some undergo PCI because of clinical constraints and experience higher long-term cardiovascular risk. The physiological rationale underlying this excess post-PCI risk remains unclear. From the perspective of post-PCI revascularization completeness and physiological results, we sought to explain the drivers of excess long-term adverse risk among patients with Favor CABG anatomy undergoing PCI. METHODS Coronary physiology based on quantitative flow ratio (QFR) was retrospectively evaluated in the randomized PANDA III trial in which all patients underwent PCI. Patients were stratified into 2 predefined groups by baseline SYNTAX score: Favor PCI or Favor CABG. Functional revascularization completeness was assessed using classic residual functional SYNTAX score (c-rFSS). Final physiological results were quantified by post-PCI QFR. Causal mediation analyses used 2-year major adverse cardiovascular events (MACE) excluding periprocedural MI as the outcome to estimate the proportion of the group-outcome association statistically accounted for by residual coronary physiological profiles. The primary endpoint was 2-year MACE, defined as the composite of all-cause death, all MI, or any ischemia-driven revascularization. RESULTS A total of 1555 patients with complete post-PCI physiological assessment constituted the final study cohort, among whom 269 (17.3%) individuals were stratified to Favor CABG group by baseline SYNTAX score. The 2-year MACE rate was significantly higher in the Favor CABG than the Favor PCI group (18.6% vs 9.2%; adjusted HR: 1.78; 95% CI: 1.27-2.50). Functional incomplete revascularization (c-rFSS >0) was substantially more prevalent among patients in the Favor CABG group (53.2% vs. 15.1%, P < 0.001). Suboptimal post-PCI physiology defined by QFR <0.90 was more frequent in Favor CABG cohort (32.0% vs 11.8%, P < 0.001). In analyses using MACE excluding periprocedural MI, the estimated proportions mediated by functional incomplete revascularization and suboptimal post-PCI physiology were 49.4% and 47.8%, respectively, and their estimated joint proportion mediated was 79.8%. Integrating c-rFSS or post-PCI QFR into clinical-anatomic risk models significantly improved discrimination and reclassification capacity for 2-year MACE (all P < 0.05). CONCLUSIONS In this post hoc analysis of an all-comers PCI trial, approximately one-fifth of patients presented with anatomic complexity warranting CABG as the preferred revascularization strategy. Favor CABG anatomy was associated with higher 2-year MACE than Favor PCI anatomy. This association may be partly explained by the higher prevalence of residual functional incomplete revascularization and suboptimal post-PCI physiology. These findings between Favor CABG and Favor PCI anatomy do not represent a head-to-head comparison and should not be interpreted as a direct comparison of revascularization modalities. TRIAL REGISTRATION URL: https://www. CLINICALTRIALS gov; Unique Identifier: NCT02017275.