Predictors of Major Bleeding Among Working-Age Adults with Atrial Fibrillation: Evaluating the Effects of Potential Drug-drug Interactions and Switching from Warfarin to Non-vitamin K Oral Anticoagulants

Abstract

Purpose This study aims to evaluate the associations between switching from warfarin to non-vitamin K oral anticoagulants (NOACs), exposure to potential drug-drug interactions (DDIs), and major bleeding events in working-age adults with atrial fibrillation (AF). Methods We conducted a retrospective cohort study using the claims database of commercially insured working-age adults with AF from 2010 to 2015. Switchers were defined as patients who switched from warfarin to NOAC; non-switchers were defined as those who remained on warfarin. We developed novel methods to calculate the number and proportion of days with potential DDIs with NOAC/warfarin. Multivariate logistic regressions were utilized to evaluate the associations between switching to NOACs, exposure to potential DDIs, and major bleeding events. Results Among a total of 4126 patients with AF, we found a significantly lower number of potential DDIs and the average proportion of days with potential DDIs in switchers than non-switchers. The number of potential DDIs (AOR 1.14, 95% CI 1.02–1.27) and the HAS-BLED score (AOR 1.64, 95% CI 1.48–1.82) were significantly and positively associated with the likelihood of a major bleeding event. The proportion of days with potential DDIs was also significantly and positively associated with risk for bleeding (AOR 1.42, 95% CI 1.03, 1.96). We did not find significant associations between switching to NOACs and major bleeding events. Conclusions The number and duration of potential DDIs and patients’ comorbidity burden are important factors to consider in the management of bleeding risk in working-age AF adults who take oral anticoagulants.

Factors Affecting Medication Adherence in Patients with Mechanical Heart Valves Taking Warfarin: The Role of Knowledge on Warfarin, Medication Belief, Depression, and Self-Efficacy

“…Oral anticoagulants, which must be taken for life after mechanical valve replacement, show therapeutic effects by maintaining adequate blood levels with the international normalized ratio (INR) of prothrombin time (PT) depending on the valve location. According to racial and sociocultural characteristics, low-dose anticoagulant therapy is recommended for Asians based on coagulation characteristics, lifestyle (including food), interactions with other drugs, and vulnerable thrombotic complications [ 2 , 3 ]. Oral anticoagulant therapy after mechanical valve replacement in Koreans requires more detailed, systematic, and continuous management [ 2 ].…”

Drug interactions of oral anticoagulants

“…In a study done by Feng et al in adult AF patients, it was found that potential drug-drug interactions were significantly lower in those who switched from warfarin to DOACs. 20 We found that patients above 60 years and presence of VTE were significant predictors of major drug interactions. However, the results of the multivariate analysis should be viewed with caution owing to the small sample size and single study centre.…”

“…3 Feng et al reported that the number of potential drug interactions and the proportion of days with potential drug interactions were significantly associated with risk of bleeding. 20 In the excessive warfarin anticoagulation (EWA) study done in AF patients, excessive alcohol consumption and reduced renal function were the strongest predictors of excessive warfarin anticoagulation, defined as INR values≥9. Recent intake of antibiotic or antifungal drugs, recent hospitalization and outpatient visit were the other significant temporary predictors of excessive anticoagulation with warfarin.…”

Predictors of bleeding event among elderly patients with mechanical valve replacement using random forest model

“…Warfarin, a vitamin K antagonist, interacts with numerous drugs and foods, and the list of interactions continues to expand. [ 24 ] Controlling anticoagulants is important for patients after mechanical valve replacement because maintenance of the correct target PT INR is essential to maintain valve function. Prescription of non-vitamin K antagonist oral anticoagulants has increased dramatically since their introduction in 2010.…”