Major Bleeding Risk in Patients With Non-valvular Atrial Fibrillation Concurrently Taking Direct Oral Anticoagulants and Antidepressants

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Non-valvular Atrial Fibrillation (n=98863). Intervention: DOACs with concurrent bupropion vs. DOACs alone. Primary outcome: Major bleeding (ARR 1.49, 95% CI 1.02-2.16, p=0.037).

Q: What does this research mean for the field?

Concurrent use of bupropion and other specific antidepressants with direct oral anticoagulants in patients with non-valvular atrial fibrillation significantly increases the risk of major bleeding compared to DOACs alone. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Kuo‐Hsuan Chang; Chiung‐Mei Chen; Chunli Wang; Hui‐Tzu Tu; Yu‐Tung Huang; Hsiu‐Chuan Wu; Chien-Hung Chang; Shang‐Hung Chang

doi:10.3389/fnagi.2022.791285

February 4, 2022Frontiers in Aging NeuroscienceOpen Access

Major Bleeding Risk in Patients With Non-valvular Atrial Fibrillation Concurrently Taking Direct Oral Anticoagulants and Antidepressants

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Key result

Combining bupropion with DOACs in NVAF is linked to ~49% higher major bleeding risk.

ARR 1.49
95% CI 1.02-2.16
P=0.037
n=98,863

Figures

Why the study?

DOACs are commonly prescribed alongside antidepressants, which may increase bleeding risk.

Does concurrent use of antidepressants with DOACs increase the risk of major bleeding in patients with non-valvular atrial fibrillation?

Study Design

Type

Cohort (n=98,863)

Structured PICO

Does concurrent use of antidepressants with DOACs increase the risk of major bleeding in patients with non-valvular atrial fibrillation?

P

Population

98,863 patients with non-valvular atrial fibrillation (AF) receiving DOACs (dabigatran, rivaroxaban, apixaban, or edoxaban) for >28 days, mean age 74.89, 56.25% male, from Taiwan. Excluded: DOACs for other indications (pulmonary embolism, DVT, mitral stenosis, joint replacement, valvular surgery), end-stage renal disease, or age <30 or >105 years.

I

Intervention

Direct oral anticoagulants (DOACs) with concurrent antidepressants (SNRI, SSRI, TCA, TeCA, or others including bupropion)

C

Comparator

Direct oral anticoagulants (DOACs) alone without concurrent antidepressants

O

Outcome

Major bleeding, identified by ICD codes at emergency department visit with a primary diagnosis of intracerebral hemorrhage (ICH), gastrointestinal or other bleedings (intraspinal, intraocular, retroperitoneal, intra-articular, pericardial, or intramuscular hemorrhage)safety

Main Result

Effect estimate: ARR 1.49 (95% CI 1.02-2.16)

Absolute Event Rate: 71.8% vs 48.33%

p-value: p=0.037

Limitations

Misclassification bias from diagnosis codes in the nationwide registration database
Lack of laboratory data regarding renal or liver function
DOAC and antidepressant dosage, duration, and compliance were not considered in the model
Potential unmeasured confounders despite extensive adjustment
Ethnic differences in bleeding risk with oral anticoagulant therapy may limit generalizability

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Implication

Concurrent use of specific antidepressants, particularly bupropion and SSRIs, with DOACs in patients with atrial fibrillation is associated with an increased risk of major bleeding and intracerebral hemorrhage.

Abstract

Direct oral anticoagulants (DOACs) are commonly prescribed with antidepressants that may increase bleeding risk. Here we assessed the association between DOACs with and without concurrent antidepressants and major bleeding risk in patients with atrial fibrillation (AF) by a retrospective cohort study included patients with AF who received prescriptions of DOACs in Taiwan's National Health Insurance database between 2012 and 2017. Adjusted rate ratio (ARR) of major bleeding was calculated by comparing incidence rate adjusted with Poisson regression and inverse probability of treatment weighting using the propensity score between patient-times with and without antidepressants. Among 98863 patients with AF, concurrent use of bupropion with DOACs increased the risks of all major bleeding (ARR: 1.49, 95% CI: 1.02-2.16) and gastrointestinal hemorrhage (ARR: 1.57, 95% CI: 1.04-2.33). An increased risk of intracerebral hemorrhage (ICH) was associated with the combinations of DOACs with selective serotonin reuptake inhibitors (SSRIs, ARR: 1.38, 95% CI: 1.08-1.76), particularly in paroxetine (ARR: 2.11, 95% CI: 1.17-3.81), and tetracyclic antidepressants (TeCAs, ARR: 1.34, 95% CI: 1.01-1.78). In subgroup analyses stratified by individual NOACs, SSRIs increased the risk of ICH in the dabigatran-treated patients (ARR: 1.55, 95% CI: 1.04-2.33). The combinations of apixaban and serotonin-norepinephrine reuptake inhibitors (SNRIs) were associated with a higher risk of all major bleeding (ARR: 1.63, 95% CI: 1.04-2.55). These results clearly indicate the drug-drug interactions between DOACs and antidepressants, which should be carefully considered when prescribing DOACs in adult patients. Careful monitoring for bleeding should be performed while concurrently prescribing DOACs with bupropion, SSRI, SNRI, and TeCA. Concomitant use of DOACs and TCAs may be a relatively safe strategy for patients with AF.

Discussion

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Cite This Study

Chang et al. (2022) conducted a cohort in Non-valvular Atrial Fibrillation (n=98,863). DOACs with concurrent bupropion vs. DOACs alone was evaluated on Major bleeding (ARR 1.49, 95% CI 1.02-2.16, p=0.037). Concurrent use of bupropion with direct oral anticoagulants in patients with non-valvular atrial fibrillation significantly increased the risk of major bleeding compared to DOACs alone (ARR 1.49).

synapsesocial.com/papers/6a18d89c04206f6c9d906676 https://doi.org/10.3389/fnagi.2022.791285

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Major Bleeding Risk in Patients With Non-valvular Atrial Fibrillation Concurrently Taking Direct Oral Anticoagulants and Antidepressants

Figures

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Major Bleeding Risk in Patients With Non-valvular Atrial Fibrillation Concurrently Taking Direct Oral Anticoagulants and Antidepressants

Figures

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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