Effect of Inflammasome Inhibitor on hsCRP in Patients After PCI

Overview

Coronary artery disease (CAD) comprises the major contributor to a global epidemic of cardiovascular disease. Patients with CAD undergoing percutaneous coronary intervention (PCI) have a high-risk for adverse clinical outcomes. Residual inflammatory risk (RIR) in patients with CAD after standardized treatment is the main cause of adverse events such as recurrent myocardial infarction, stroke, and death, which has gained much interest in recent years. Inflammation plays an important role in the development of CAD. However, several randomized controlled clinical studies (RCT) of anti-inflammatory treatments ended in failure previously. Since 2017, the success of three large-scale RCTs (CANTOS, COLCOT and LoDoCo2) points to targeting the NLRP3 - IL-1 β- IL-6 pathway for anti-inflammatory treatment of CAD. The inhibition of this pathway eventually leads to the decrease of high-sensitivity C-reactive protein (hsCRP), consistent with an anti-inflammatory effect. Therefore, the change of hsCRP may serve as a biomarker to screen anti-inflammatory drugs in this pathway. Targeting the NLRP3 - IL-1 β- IL-6 pathway with monoclonal antibodies is limited by high prices of the biological agents. Thus, researchers focused on the upstream molecule NLRP3. Currently, NLRP3 inhibitors that are clinically available include colchicine , tranilast and oridonin. Although several studies have indicated the effective effects of colchicine in CAD, the other two NLRP3 inhibitors lack sufficient data on anti-inflammatory treatment of CAD. Therefore, we intend to use NLRP3 inhibitors (colchicine, tranilast and oridonin) to treat patients after PCI for 4 weeks, compare the changes of hsCRP, and explore the effectiveness and safety of these different drugs, and screen the optimal anti-inflammatory drugs for coronary heart disease.