Associations between ticagrelor use and the risk of infections: A Mendelian randomization study.

Abstract

We conducted a Mendelian randomization (MR) study to elucidate the anti-infective effects of ticagrelor. Single-nucleotide polymorphisms (SNPs) associated with serum levels of ticagrelor or its major metabolite AR-C124910XX (ARC) in the PLATelet inhibition and patient Outcomes trial were selected as genetic proxies for ticagrelor exposure. Positive control analyses indicated that genetically surrogated serum ticagrelor levels (six SNPs) but not ARC levels (two SNPs) were significantly associated with lower risks of coronary heart disease. Therefore, the six SNPs were used as genetic instruments for ticagrelor exposure, and the genome-wide association study data for five infection outcomes were derived from the UK Biobank and FinnGen consortium. The two-sample MR analyses based on inverse variance-weighted methods indicated that genetic liability to ticagrelor exposure could reduce the risk of bacterial pneumonia (odds ratio [OR]: 0.82, 95% confidence interval [CI]: 0.71-0.95, P = 8.75E-03) and sepsis (OR: 0.83, 95% CI: 0.73-0.94, P = 3.69E-03); however, no causal relationship between ticagrelor exposure and upper respiratory infection, pneumonia, and urinary tract infection was detected. Extensive sensitivity analyses corroborated these findings. Our MR study provides further evidence for the preventive effects of ticagrelor on bacterial pneumonia and sepsis.