Bleeding risk in patients with atrial fibrillation treated with combined anti-platelet and non-vitamin K antagonist oral anticoagulant therapy

Abstract

Background:The use of non-vitamin K antagonist oral anticoagulants (NOACs) in patients with non-valvular atrial fibrillation (AF) has been increasing. Accordingly, the combined use of antiplatelet agents (APT) and NOAC therapy is commonly encountered in clinical practice. The purpose of this study was to compare the clinical outcomes between combination therapy (NOAC and APT) vs. monotherapy (NOAC only) in patients with AF. Methods: We retrospectively analyzed patients who were prescribed NOACs between January 2012 and December 2016. The primary outcome was major bleeding and any bleeding events, and the secondary outcomes were stroke/systemic embolic (SE) events and major adverse cardiac events (MACE). Results: Of the 1068 participants, there were 264 (24.7%) patients in the combination therapy group. The prevalence of diabetes (p = 0.017) and history of stroke and transient ischemic attacks (p < 0.001) was higher in the combination group than in the monotherapy group. During the mean 14.6 ± 9.8 months of followup, the incidence of any bleeding was significantly higher in the combination therapy group than in the monotherapy group (p < 0.001). The rate of major bleeding, stroke/SE, and MACE between the two groups was similar. The rate of under-dosage NOAC prescriptions was higher in the combination therapy group than in the monotherapy group (p = 0.024). Conclusions: The combination therapy group had higher incidences of any bleeding events compared to the monotherapy in patients with appropriate dosing. However, there was no difference in stroke/SE, and MACE. The bleeding risk in AF patients taking the combination of NOACs and APT should be carefully evaluated.

An ADR pharmaceutical care for severe gastrointestinal bleeding of rivaroxaban in a patient with non-valvular atrial fibrillation based on TDM and genetic testing

“…The main drugs used in this case were rivaroxaban, combined with aspirin enteric-coated tablets and amlodipine atorvastatin calcium tablets. The use of antiplatelet drugs is a component of the HAS-BLED score, and aspirin combined with NOACs for the treatment of nonvalvular AF increases the risk of bleeding in patients who are susceptible to lifethreatening bleeding [25] . Although studies have found no association between statin use and increased risk of bleeding [26,27] , it was considered that atorvastatin calcium tablets may irritate the gastric mucosa, leading to side effects such as abdominal pain and bloating.…”

Effect of ABCB1 gene variants on rivaroxaban pharmacokinetic and hemorrhage events occurring in patients with non‐valvular atrial fibrillation

“…The most bleeding events occurred in the first few days after administration (Lhteenmki et al., 2012). Although patients received an under‐dose of rivaroxaban at the initial treatment to avoid bleeding events, the risk of bleeding events also increased especially for patients with atherosclerotic cardiovascular diseases and on a combination therapy (Shin et al., 2022) (warfarin and antiplatelet therapy). Studying the time of bleeding after administration was helpful for improving the clinical safety and achieving clinical benefits.…”

“…Rivaroxaban (RIV) plays a crucial role in NVAF routine anticoagulation care. It causes rapid anticoagulation by directly targeting clotting factors which reduces potential food effects and drug interactions (Bertoletti et al., 2017; Kanuri & Kreutz, 2019; Stampfuss et al., 2013). Favorable pharmacodynamic and pharmacokinetic properties are proposed for rivaroxaban and it does not require continuous therapeutic monitoring.…”

“…Differing from other NOACs, rivaroxaban produced non-linear pharmacokinetic properties with different doses. The bioavailability decreased with an increase of dosage, especially 15-20 mg qd (Harder, 2014;Stampfuss et al, 2013). Several studies revealed that the genotype variation of ABCB1 and CYP450 enzymes were associated with the rivaroxaban plasma concentration (Fernandez et al, 2021;Gouin-Thibault et al, 2017;Zhao et al, 2022).…”

“…interactions (Bertoletti et al, 2017;Kanuri & Kreutz, 2019;Stampfuss et al, 2013). Favorable pharmacodynamic and pharmacokinetic properties are proposed for rivaroxaban and it does not require continuous therapeutic monitoring.…”