Abstract Body (Do not enter title and authors here): Introduction
Historically, the pathogenesis of atherosclerotic disease has been characterized as an inflammatory process that drives the formation, progression, and rupture of plaques. Despite the recognized role of the immune response, current guidelines primarily emphasize statin and non-statin lipid lowering agents for the prevention of atherosclerotic disease. However, the utilization of anti-inflammatory agents and their effects on inflammation with respect to the attenuation of atherosclerosis has been recently highlighted in the literature.

Aim
We aimed to investigate the role of immunomodulating agents in the prevention of atherosclerotic disease by means of a systematic review.

Methods
We conducted a systematic search of MEDLINE, Cochrane, and Scopus databases through June 2024, for randomized control trials (RCTs) that assessed immunomodulating agents on outcomes of cardiovascular disease (CVD). Keywords included "anti-inflammatory therapy”, “immunomodulator therapy”, and “atherosclerotic disease”. Inclusion criteria involved participants aged 19 years and older with CVD and studies that assessed major adverse cardiovascular events (MACE), or atherosclerotic biomarkers.

Results
Five RCTs were included in our systematic review, including CANTOS, COLCOT, LoDoCo2, RESCUE, and CIRT. Two RCT's evaluated immunomodulating agents, including the CANTOS trial which assessed canakinumab, an IL-1β inhibitor and the RESCUE trial which assessed ziltivekimab, an IL-6 inhibitor. The COLCOT and LoDoCo2 trials assessed colchicine while CIRT assessed methotrexate. All trials assessed the primary endpoint of MACE, except the RESCUE trial. The primary endpoint for the RESCUE trial was the percent change in high sensitivity CRP. All trials, except CIRT had statistically significant reductions in their primary endpoints.

Conclusion:
The advancements in targeted immune therapies offer promising new avenues in cardiovascular medicine. Our systematic review of RCTs suggests that anti-inflammatory agents have a beneficial role in the reduction of cardiovascular events and the progression of CVD in patients with atherosclerotic disease. While the majority of the included RCTs support the use of these agents, the heterogeneity in the individual studies emphasize the need for further research to investigate the role of immunomodulating agents on CVD outcomes.