Dataset Information

Non-bleeding Adverse Events with the Use of Direct Oral Anticoagulants: A Sequence Symmetry Analysis.

ABSTRACT:

Introduction

Postmarketing pharmacovigilance reports have raised concerns about non-bleeding adverse events associated with direct oral anticoagulants (DOACs), but only limited results are available from large claims databases.

Objective

The aim of this study was to assess the potential association between DOAC initiation and the onset of four types of non-bleeding adverse events by sequence symmetry analysis (SSA).

Methods

SSA was performed using nationwide data from the French National Healthcare databases (Régime Général, 50 million beneficiaries) to assess a cohort of 386,081 DOAC new users for the first occurrence of four types of non-bleeding outcomes: renal, hepatic, skin outcomes identified by using hospitalization discharge diagnoses, and gastrointestinal outcomes by using medication reimbursement. Asymmetry in the distribution of each investigated outcome occurring before and after initiation of DOAC therapy was used to test the association between DOAC therapy and these outcomes. SSA inherently controls for time-constant confounders, and adjusted sequence ratios were computed after correcting for temporal trends. Negative (glaucoma) and positive (bleeding, depressive disorders) control outcomes were used and analyses were replicated on a cohort of 310,195 patients initiating a vitamin K antagonist (VKA).

Results

This study demonstrated the expected positive association between either DOAC or VKA therapy and hospitalised bleeding and initiation of antidepressant therapy, while no association was observed between either DOAC or VKA therapy and initiation of antiglaucoma medications. For DOAC therapy, signals were the associations with hepatic outcomes, including acute liver injury [for the 3-month time window, aSR₃?=?2.71, 95% confidence interval (CI) 1.79-4.52]; gastrointestinal outcomes, including initiation of drugs for constipation and antiemetic drugs (aSR₃?=?1.31, 95% CI 1.27-1.36; and 1.17, 95% CI 1.12-1.22, respectively); and kidney diseases (aSR₃?=?1.33, 95% CI 1.29-1.37).

Conclusion

Results of this nationwide study suggest that DOACs are associated with rare but severe liver injury and more frequent gastrointestinal disorders. A low risk of kidney injury with DOAC therapy can also not be excluded.

SUBMITTER: Maura G

PROVIDER: S-EPMC6061378 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Publications

Non-bleeding Adverse Events with the Use of Direct Oral Anticoagulants: A Sequence Symmetry Analysis.

Maura Géric G Billionnet Cécile C Coste Joël J Weill Alain A Neumann Anke A Pariente Antoine A

Drug safety 20180901 9

<h4>Introduction</h4>Postmarketing pharmacovigilance reports have raised concerns about non-bleeding adverse events associated with direct oral anticoagulants (DOACs), but only limited results are available from large claims databases.<h4>Objective</h4>The aim of this study was to assess the potential association between DOAC initiation and the onset of four types of non-bleeding adverse events by sequence symmetry analysis (SSA).<h4>Methods</h4>SSA was performed using nationwide data from the F ...[more]

PMID: 29714004

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Project description:Objectives: The purpose of our study is to investigate the effects of apolipoprotein B (APOB) and APOE gene polymorphisms on bleeding complications in patients receiving direct oral anticoagulants (DOACs). Methods: A total of 16 single nucleotide polymorphisms (SNPs) in 468 patients were genotyped. Six SNPs of ABCB1 (rs3842, rs1045642, rs2032582, rs1128503, rs3213619, and rs3747802), one SNP of CYP3A5 (rs776746), seven SNPs of APOB (rs1042034, rs2163204, rs693, rs679899, rs13306194, rs13306198, and rs1367117), and two SNPs of APOE (rs429358 and rs7412) were analyzed by a TaqMan genotyping assay. Multivariable logistic regression analysis with selected variables was performed for the construction of a risk scoring system. Two risk scoring systems were compared (demographic factors only vs. demographic factors and genetic factors). Results: In the multivariable analyses, two models were constructed; only demographic factors were included in Model I and both demographic factors and genetic factors in Model II. Rivaroxaban and anemia showed significant association with bleeding in both models. Additionally, ABCB1 rs3842 variant homozygote carriers (CC) and APOB rs13306198 variant allele carriers (AG, AA) had a higher risk of bleeding risk compared with that of wild-type allele carriers (TT, TC) and wild-type homozygote carriers (GG), respectively. Whereas the area under the receiver operating characteristic curve (AUROC) value using demographic factors only was 0.65 (95% confidence interval (CI): 0.56-0.74), the AUROC increased to 0.72 by adding genetic factors (95% CI: 0.65-0.80). The predicted bleeding risks of bleeding in patients with 0, 1, 2, 3, 4, 5, 6, 7 and 8 points from the logistic regression curve were 0.8%, 2.0%, 5.4%, 5.2%, 12.5%, 26.9%, 47.0%, 64.3% and 82.3%, respectively. Conclusions: The study results can be used for enhancing individualized treatment strategies in patients taking DOACs, helping clinicians predict the bleeding risk.

Project description:BackgroundStatins are frequently prescribed with direct oral anticoagulants (DOACs), and previous studies have raised concerns about the increased risk of intracerebral hemorrhage or other major bleeding in concurrent statins and DOACs use. The objective of this study is to evaluate the risk of major bleeding in non-valvular atrial fibrillation patients taking DOACs with or without statins.MethodsThis nationwide, retrospective cohort study used data from the Taiwan National Health Insurance Research Database, enrolled a total of 90,731 non-valvular atrial fibrillation patients receiving rivaroxaban, dabigatran, apixaban or edoxaban from January 1st, 2012 to December 31st, 2017. Major bleeding was defined as a hospitalization or emergency department visit with a primary diagnosis of intracerebral hemorrhage, gastrointestinal tract bleeding, urogenital tract bleeding, or other sites of bleeding. Adjusted incidence rate ratios (IRR) and differences of major bleeding between person-quarters of DOACs with or without statins were estimated using a Poisson regression and inverse probability of treatment weighting using the propensity score.Results50,854 (56.0%) of them were male with a mean age of 74.9 (SD, 10.4) years. Using DOACs without statins as a reference, the adjusted IRR for all major bleedings in concurrent use of DOACs and statins was 0.8 (95% CI 0.72-0.81). Lower major bleeding risk was seen in both low-to-moderate-intensity statins (IRR: 0.8, 95% CI 0.74-0.84) and high-intensity statins (IRR: 0.8, 95% CI 0.74-0.88). Concurrent use of DOACs and statins decreased the risk for intracerebral hemorrhage with an IRR of 0.8 (95% CI 0.66-0.93), and gastrointestinal tract bleeding with an IRR of 0.7 (95% CI 0.69-0.79). The protective effect of statins on intracerebral hemorrhage was observed only in female patients (IRR 0.67, 95% CI 0.51-0.89), but not in male patients (IRR 0.87, 95% CI 0.70-1.08).ConclusionsAmong non-valvular atrial fibrillation patients who were taking DOACs, concurrent use of statins decreased major bleeding risk, including intracerebral hemorrhage and gastrointestinal tract bleeding. Considering this and other cardioprotective effects, statins should be considered in all eligible patients prescribed with DOACs.

Dataset Information

Non-bleeding Adverse Events with the Use of Direct Oral Anticoagulants: A Sequence Symmetry Analysis.

Introduction

Objective

Methods

Results

Conclusion

Publications

Non-bleeding Adverse Events with the Use of Direct Oral Anticoagulants: A Sequence Symmetry Analysis.

Similar Datasets

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