Treatment with the oral thrombin inhibitor dabigatran was found to be associated with a significantly lower incidence of Staphylococcus aureus bacteremia (SAB) compared with treatment with factor Xa-inhibitors, according to the results of observational cohort study published in Clinical Infectious Diseases.

Dabigatran has been shown to reduce virulence of S aureus in both in vitro and in vivo models, but whether it reduces risk of bacteremia in humans has yet to be determined. To address this, the incidence rate of SAB in patients with atrial fibrillation treated with dabigatran compared with patients treated with the factor Xa-inhibitors rivaroxaban, apixaban, and edoxaban was assessed.

Investigators identified 112,537 patients with atrial fibrillation who initiated treatment with direct oral anticoagulants between August 2011 and December 2017 from Danish nationwide registries. During a median follow-up of 2 years, 186 and 356 patients undergoing treatment with dabigatran or a factor Xa-inhibitor, respectively, were admitted for treatment of SAB. The crude incidence rate of SAB in the dabigatran group of 22.8 (95% CI, 19.7-26.3) events per 10,000 person-years was lower compared with the Xa-inhibitor group, which was 33.8 (95% CI, 30.5-37.6) events per 10,000 person-years. In adjusted analyses, dabigatran was also associated with significantly lower incidence rate of SAB compared with factor Xa-inhibitors (incidence rate ratio 0.76; 95% CI, 0.63-0.93).

The main strength of this study, according to investigators, is the completeness of data from nationwide administrative registries and the Danish Staphylococcal Bacteremia Database. However, they caution that the findings need to be interpreted in light of several limitations, including that the observational nature of the work precludes assessment of cause-and-effect relationships. Residual confounding also cannot be excluded despite adjustments for potential confounders. The investigators admit “it is likely that these adjustments were not sufficient to even out the differences between the groups, including differences in age and prevalence of chronic kidney disease.” Furthermore, they state that confounding by indication cannot be omitted in pharmacoepidemiologic studies, but they did attempt to minimize the impact by restricting the selection of the study population to a more homogeneous population.


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The study was also not powered to detect a significant difference between dabigatran and factor Xa inhibitors with regard to the numerically lower incidence rate of the S aureus endocarditis outcome due to the low rate of S aureus endocarditis in the study population. They also note that during the study period, the incidence of SAB in the Danish general population increased, and the proportion of patients initiating dabigatran treatment decreased. To minimize the impact of these time trends, a sensitivity analysis in which the inclusion period was restricted to January 1, 2013, through December 30, 2017, was performed.

According to these results, the investigators did conclude that dabigatran was associated with a significantly lower incidence rate of SAB and believe “this finding may have important implications for the evolvement of prevention and treatment strategies for SAB and warrant further investigation.”

Reference

Butt JH, Fosbøl EL, Verhamme P, et al. Dabigatran and the risk of Staphylococcus aureus bacteremia – A nationwide cohort study [published online June 1, 2020]. Clin Infect Dis. doi:10.1093/cid/ciaa661