Reply to: “The “Plaque Burden” of Proof: Why Mechanisms Matter in Invasive Coronary Artery Disease Treatment”

We thank Drs. Mukharyamov, Reinartz, and Doenst for their interest and for commenting on our manuscript ‘Outcomes with revascularization vs. medical therapy according to plaque burden from coronary computed tomography angiography’.1 We agree on the different therapeutic mechanisms of action of coronary revascularization with percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). Since our manuscript was designed as hypothesis generating ‘proof-of-concept’ analysis, on the prognostic impact of plaque burden independent of ischaemia and a potential alternative target for revascularization, we had not performed subgroup analyses on the effects of revascularization modality. But, we agree with the authors, that this concept requires further investigation. Therefore, according to the suggestion, we performed additional analyses on the interaction between per-vessel percent atheroma volume (PAV) and revascularization with either PCI or CABG. In our cohort, a total of 286 patients underwent revascularization, out of which 216 patients with PCI and 70 with CABG. Among the 2381 patients undergoing CABG or medical therapy, there were 212 composite endpoint events (all-cause death, myocardial infarction, or unstable angina pectoris). There was significant interaction between CABG and continuous per-vessel PAV (P = 0.019), whereas among the 2527 patients undergoing PCI or medical therapy with 244 events, the interaction was not significant (P = 0.864). In addition, we adjusted the interaction model for age, sex, per-vessel ischaemia, coronary artery calcium score, antiplatelet or lipid-lowering drugs, and typical angina pectoris. Results remained consistent with significant interaction between CABG and per-vessel PAV (P = 0.041), but not PCI and per-vessel PAV (P = 0.639).