Do Apixaban Plasma Levels Relate to Bleeding? The Clinical Outcomes and Predictive Factors for Bleeding in Patients with Non-Valvular Atrial Fibrillation

Abstract

Apixaban can significantly prevent stroke events in patients with non-valvular atrial fibrillation (NVAF), as can be observed from the large, randomized, controlled trial conducted in the present study. However, the real-world evidence of bleeding events related to the apixaban plasma levels in Asian populations is limited. This study aimed to investigate the apixaban plasma levels and clinical outcomes among NVAF patients receiving apixaban, including determining the risk factors associated with bleeding during routine care. Seventy-one patients were included in the study. The median values were 112.79 (5–95th percentiles: 68.69–207.8) μg/L and 185.62 (5–95th percentiles: 124.06–384.34) μg/L for the apixaban trough (Ctrough) and apixaban peak plasma levels (Cpeak), respectively. Stroke and bleeding were found in 8 (11.27%) and 14 patients (19.72%), respectively. There was no statistical significance for Ctrough and Cpeak in the stroke and non-stroke groups, respectively. The median of Ctrough (139.15 μg/L) in patients with bleeding was higher than that in the non-bleeding group (108.14 μg/L), but there was no statistical significance. However, multivariate analyses showed that bleeding history (odds ratio (OR): 17.62; 95% confidence interval (CI): 3.54–176.64; and p-value = 0.002) and Ctrough (OR: 1.01; 95%: CI 1.00–1.03; and p-value = 0.038) were related to bleeding events. Almost all of the patients presented apixaban plasma levels within the expected range. Interestingly, bleeding events were associated with the troughs of the apixaban plasma levels and bleeding history.

Frailty as a Marker for the Plasma Concentrations of Direct Oral Anticoagulants in Older Patients: Results of an Exploratory Study

“…DOAC concentrations are related to effect. Higher concentrations have been associated with bleeding events [ 33 ], while lower concentrations appear to predispose to the occurrence of strokes [ 34 ], albeit a therapeutic range for DOAC concentrations remains to be defined [ 35 ]. A number of factors can contribute to impaired drug clearance such as renal and liver impairment, sarcopenia, and hypoalbuminemia, many of which are present in frail patients [ 36 ].…”

Tailored Direct Oral Anticoagulation in Patients with Atrial Fibrillation: The Future of Oral Anticoagulation?

“…In our previous analyses [ 7 , 8 ], there were significantly higher rivaroxaban levels at the time of bleeding compared to the trough levels of patients who did not have complications during rivaroxaban administration (245.9 ± 150.2 ng/mL versus 52.5 ± 36.4 ng/mL; p < 0.001), and rivaroxaban levels tended to be lower in those experiencing embolic stroke (42.7 ± 31.9 ng/mL); however, the variability in drug plasma levels was the highest in rivaroxaban-treated patients. For apixaban, Limcharoen et al [ 22 ] reported an association between apixaban trough levels and the risk of bleeding. In apixaban-treated patients with bleeding, apixaban trough levels of 139.15 ng/mL were reported.…”

“…These levels are lower than our previous observation of apixaban levels of 311.8 ± 142.5 ng/mL at the time of a bleeding event [ 7 ]. It is interesting that, in the study performed by Limcharoen et al, almost all the patients presented apixaban plasma levels within the expected range, which was defined as a range of 34.0–230.0 ng/mL for trough and 69.0–321.0 ng/mL for peak drug levels [ 22 ]. The ranges were derived from a pharmacokinetic study with apixaban [ 23 ].…”