Abstract Body (Do not enter title and authors here): Background: Inflammation is a critical factor in the development of coronary artery disease. The systemic inflammatory response index (SIRI) is a novel biomarker of inflammation. Studies have shown that SIRI is associated with the severity of coronary artery disease. However, there is currently a lack of research on the relationship between SIRI and adverse outcomes in patients with multivessel coronary artery disease. Our study aimed to investigate the correlation between SIRI and long-term mortality risk in patients with triple-vessel coronary disease (TVD) and explore the interaction between SIRI and treatment strategies.

Methods: After excluding patients with missing data or loss to follow-up, a total of 8559 patients with TVD were included in our study. Based on their SIRI levels during hospitalization, patients were evenly divided into three groups (SIRI-L, SIRI-M, and SIRI-H). All patients received appropriate treatment, including medical therapy alone (MT), percutaneous coronary intervention (PCI), or coronary artery bypass grafting (CABG). The primary endpoint was all-cause death. SIRI was calculated by the formula: neutrophil counts × monocyte counts / lymphocyte counts.

Results: During a median follow-up of 6.58 years, a total of 1264 all-cause deaths (14.8%) were recorded. Elevated SIRI was significantly associated with increased mortality rates (11.1%, 14.6%, and 18.6% in the SIRI-L, SIRI-M, and SIRI-H groups, respectively). The risk of all-cause mortality was significantly higher in the SIRI-M and SIRI-H groups compared to the SIRI-L group (adjusted HR: 1.203, 95% CI: 1.037-1.395, p=0.015; adjusted HR: 1.400, 95% CI: 1.212-1.617, p<0.001; respectively). In elderly patients, the relationship between elevated SIRI and the risk of all-cause mortality was more pronounced, while it attenuated in younger patients. Additionally, it is noteworthy that there was an interaction between SIRI and treatment strategy (p=0.037). In patients of the SIRI-L group, there was no significant difference between PCI and CABG treatment. However, in patients of the SIRI-M and SIRI-H groups, CABG shows a significant survival advantage over PCI.

Conclusion: Evaluating SIRI may help identify high-risk groups among patients with triple-vessel coronary disease and guide the selection of treatment strategies.