Dataset Information

Impact of drug interactions with direct oral anticoagulants on mortality in elderly with atrial fibrillation during the COVID-19 pandemic Impacto de la interaccion de farmacos con los anticoagulantes orales directos en la mortalidad de pacientes mayores con fibrilacion auricular durante la pandemia por COVID-19

ABSTRACT:

Objective

To evaluate the effect of drug interactions with chronic direct oral anticoagulants (DOAC) on mortality in older atrial fibrillation (AF) patients during the Coronavirus disease 2019(COVID-19) pandemic.

Methods

We followed a total of 601 elderly patients (65 years of age) from the NOEL-Drug Registry cohort who were referred to a tertiary outpatient clinic between 9 March 2020 and 1 March 2021. We recorded clinical characteristics and medications for the last 3 months. In addition, all drug interactions were identified using Lexicomp®. Finally, we recorded retrospectively all death events, COVID-19 diagnosis, and relevant deaths from the database at the end of the study. According to logistic regression, we performed propensity score (PS) matching to reduce potential bias. Factors associated with total mortality in the 12 months were analyzed using multivariable Cox proportion hazard analysis.

Results

The mean age [standard deviation (SD)] was 74.5 (±6.9), and the male/female ratio was 337/264. The prevalence of total mortality was 16.9% (n = 102). A total of 4472 drugs were analyzed for DOAC interaction. 81.8% of older AF patients were not at risk in terms of potential interaction. In the Cox proportional hazard model after PS-matching, previous DOAC use with class X interaction was associated with significantly higher mortality risk (adjusted hazard ratio: 2.745, 95% confidence interval: 1.465–5.172, p = 0.004).

Conclusions

Our study showed that while most co-medications do not have significant interactions with DOACs, few serious drug interactions contribute to mortality in elderly patients with AF during the pandemic.

SUBMITTER: Ersoy I

PROVIDER: S-EPMC9283695 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Project description:Essentials Currently, DOACs are given at fixed doses and do not require laboratory monitoring. Direct oral anticoagulant-specific measurements were performed at trough and peak. Patients who developed bleeding events showed higher DOAC plasma levels at peak. This study suggests the need of a more accurate DOAC dose assessment.BackgroundDirect oral anticoagulants (DOACs) are administered at fixed dose. The aim of the study was to evaluate the relationship between DOAC C-trough or C-peak plasma levels and bleeding complications in patients with non-valvular atrial fibrillation (NVAF).MethodsFive hundred sixty five consecutive naive NVAF patients were enrolled. The DOAC measurements at C-trough and at C-peak (available in 411 patients) were performed at steady state, within the first month of treatment. Major bleeding (MB), clinically relevant non-major bleeding (CRNMB), and minor bleeding (MinB), occurring during 1 year of follow-up after blood sampling, were recorded. For each DOAC, interval of C-trough and C-peak levels was subdivided into four equal classes and results were attributed to these classes; the median values of results were also calculated.ResultsTwo hundred eight patients were on apixaban, 185 on dabigatran, and 172 on rivaroxaban. For 1-[qqqdeletezzz] year follow up for all patients, we observed: 19 MB (3.36%), 6 CRNMB (1.06%), and 47 MinB (8.31%). The prevalence of bleeding patients with anticoagulant levels in the upper classes of C-peak activity (II + III + IV) was higher than that in the lowest class. Normalized results of C-peak levels were higher in patients with bleeding than in those without bleeding.ConclusionsBleeding complications during DOAC treatment were more frequent among atrial fibrillation (AF) patients with higher C-peak anticoagulant levels. In addition to a previous study that showed an increased risk of thrombotic complications in the patients with low C-trough levels, this study seems to indicate that patients with NVAF on DOACs would need a more accurate definition of their optimal therapeutic window.

Project description:Background: Direct oral anticoagulants (DOACs) have been widely used in patients with atrial fibrillation (AF) for antithrombotic prophylaxis, which were shown to have a favorable risk-benefit profile. However, there are no guidelines for the use of DOACs in elderly patients (aged ≥75 years) with AF, which creates uncertainty about the optimal antithrombotic treatment in these patients. Methods: After comprehensively searching Embase, PubMed, and Cochrane databases, five phase III randomized controlled trials involving 28,137 elderly participants were included in this study. The efficacy outcome was stroke or systemic embolism, and the safety outcome was major bleeding. We conducted a network meta-analysis by using a Bayesian random-effect model for the first time to evaluate the efficacy and safety of main DOACs (apixaban, edoxaban, rivaroxaban, and dabigatran) and warfarin in elderly patients with AF. Hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) were used to assess the effect of drugs on efficacy and safety. The rank probabilities were used to reflect the hierarchy of drugs, and a larger rank probability value symbolized a better rank of drugs. Results: In the prophylaxis of stroke or systemic embolism, apixaban was found to be the best among DOACs compared to warfarin (HR, 0.71; 95% CI: 0.33-1.50), though this finding was not statistically significant. Apixaban ranked the best (rank probabilities, 41.2%) in efficacy of drugs, followed by rivaroxaban, edoxaban, dabigatran, and warfarin (rank probabilities, 31.8, 15.9, 10.9, and 0.2%, respectively). In reducing the risk of major bleeding, apixaban was found to be the best among DOACs too, compared to warfarin (HR, 0.64; 95% CI: 0.33-1.30), though this finding was not statistically significant. In safety, apixaban ranked the best (rank probabilities, 71.4%), followed by edoxaban, dabigatran, warfarin, and rivaroxaban (rank probabilities, 21.0, 5.8, 0.9, and 0.8%, respectively). Conclusions: DOACs showed a lower incidence of stroke/systemic embolism and major bleeding compared with warfarin in antithrombotic therapy in elderly patients (aged ≥75 years), with apixaban being the best of those interventions. Therefore, apixaban should be given priority as an anticoagulant in stroke prevention for elderly patients with AF.