Factors influencing trough and 90-minute plasma dabigatran etexilate concentrations among patients with non-valvular atrial fibrillation

• Plasma concentration of dabigatran (PDC) and APTT varies widely among patients.
• We sought factors that affect PDC and relationship between PDC and APTT and PDC and D-dimer.
• Renal function and CHA2DS2-Vasc score affect plasma dabigatran concentration and PDC positively correlates with APTT.
• Higher D dimer levels are associated with the lower PDC.

IntroductionDabigatran etexilate, a direct oral anti-coagulation agent, is used in the prevention of thromboembolism in patients with non-valvular atrial fibrillation (NVAF). However, for reasons that are not fully understood, plasma dabigatran etexilate concentrations (PDC) vary significantly among patients.MethodsWe measured trough and 90 min PDC in 98 patients with NVAF. To elucidate the cause of variations in PDC, we determined correlations between PDC and various factors including renal function, co-administration of a P-glycoprotein inhibitor, and the effects of three single nucleotide polymorphisms (SNPs) of the P-glycoprotein intestinal efflux transporter. To further determine the cause of PDC variations, we examined the relationship between PDC, activated partial prothrombin time (APTT), and D-dimer (DD) levels, which are surrogate markers for thrombotic risk.ResultsMultivariate analysis showed significant relations among creatinine, creatinine clearance, and CHA2D2-VaSc scores (p = 0.04, p = 0.01, and p = 0.04, respectively). In addition, creatinine and creatinine clearance were significantly correlated with trough and 90 min PDC (p < 0.01), respectively. There was a clear linear relation between PDC and APTT, but not DD levels. However, higher DD levels (> 0.5 μg/mL) were associated with lower trough and 90 min PDCs.ConclusionsRenal function and CHA2D2-VaSc scores affect PDC, suggesting these may be primary factors influencing the wide variation observed in PDCs under these conditions. Variations in APTT can primarily be explained by variations in PDC; patients with lower PDCs may have a higher risk of thromboembolism events.