For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
0
views
26
references
 Top references
cited by
8
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      658
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Concomitant Use of Direct Oral Anticoagulants and Antiepileptic Drugs: A Prospective Cohort Study in Patients with Atrial Fibrillation

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background

          European guidelines do not recommend the use of carbamazepine, levetiracetam, phenobarbital, phenytoin, topiramate and valproic acid in patients taking direct oral anticoagulants (DOACs). Little is known regarding the clinical relevance of the interaction between DOACs and antiepileptic drugs.

          Objectives

          To evaluate the incidence of thromboembolic and bleeding events in patients with non-valvular atrial fibrillation (AF) concurrently treated with DOACs and antiepileptic drugs.

          Methods

          This is a prospective multicentre cohort study of patients with non-valvular AF concurrently treated with DOACs and antiepileptic drugs. The primary outcome was ischaemic stroke/transient ischaemic attack (TIA)/systemic embolism (SE). Secondary outcome was major bleeding (MB). Incidence rates (% patient-year) were evaluated for the study outcomes.

          Results

          Overall, 91 patients were included. Mean age was 78 ± 9.5 years, 49.5% were female. Mean CHA 2DS 2-VASc score was 4.76 ± 1.59 and mean HAS-BLED was 2.67 ± 1.26. Overall, 41, 20, 11, 10 and 9 out of 91 patients were treated with levetiracetam, valproic acid, phenobarbital, carbamazepine and other antiepileptic drugs, respectively. During a median follow-up of 17.5 ± 14.5 months, stroke/TIA/SE occurred in 9 patients (5.7% patient-year) and MB in 3 patients (1.9% patient-year). Ischaemic stroke was fatal in 3 patients (1.9% patient-year) and MB in one patient (0.6% patient-year).

          Conclusion

          In this cohort, patients with non-valvular AF treated with DOACs and antiepileptic drugs appear to have a relatively high rate of thromboembolic events.

          Related collections

          Most cited references26

          • Record: found
          • Abstract: found
          • Article: not found

          Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation.

          Gregory Y. H. Lip, Robby Nieuwlaat, Ron Pisters … (2010)
          Contemporary clinical risk stratification schemata for predicting stroke and thromboembolism (TE) in patients with atrial fibrillation (AF) are largely derived from risk factors identified from trial cohorts. Thus, many potential risk factors have not been included. We refined the 2006 Birmingham/National Institute for Health and Clinical Excellence (NICE) stroke risk stratification schema into a risk factor-based approach by reclassifying and/or incorporating additional new risk factors where relevant. This schema was then compared with existing stroke risk stratification schema in a real-world cohort of patients with AF (n = 1,084) from the Euro Heart Survey for AF. Risk categorization differed widely between the different schemes compared. Patients classified as high risk ranged from 10.2% with the Framingham schema to 75.7% with the Birmingham 2009 schema. The classic CHADS(2) (Congestive heart failure, Hypertension, Age > 75, Diabetes, prior Stroke/transient ischemic attack) schema categorized the largest proportion (61.9%) into the intermediate-risk strata, whereas the Birmingham 2009 schema classified 15.1% into this category. The Birmingham 2009 schema classified only 9.2% as low risk, whereas the Framingham scheme categorized 48.3% as low risk. Calculated C-statistics suggested modest predictive value of all schema for TE. The Birmingham 2009 schema fared marginally better (C-statistic, 0.606) than CHADS(2). However, those classified as low risk by the Birmingham 2009 and NICE schema were truly low risk with no TE events recorded, whereas TE events occurred in 1.4% of low-risk CHADS(2) subjects. When expressed as a scoring system, the Birmingham 2009 schema (CHA(2)DS(2)-VASc acronym) showed an increase in TE rate with increasing scores (P value for trend = .003). Our novel, simple stroke risk stratification schema, based on a risk factor approach, provides some improvement in predictive value for TE over the CHADS(2) schema, with low event rates in low-risk subjects and the classification of only a small proportion of subjects into the intermediate-risk category. This schema could improve our approach to stroke risk stratification in patients with AF.
          Article 0 comments Cited 1015 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients.

            S Schulman, C Kearon (2005)
            Summary. A variety of definitions of major bleeding have been used in published clinical studies, and this diversity adds to the difficulty in comparing data between trials and in performing meta-analyses. In the first step towards unified definitions of bleeding complications, the definition of major bleeding in non-surgical patients was discussed at the Control of Anticoagulation Subcommittee of the International Society on Thrombosis and Haemostasis. Arising from that discussion, a definition was developed that should be applicable to studies with all agents that interfere with hemostasis, including anticoagulants, platelet function inhibitors and fibrinolytic drugs. The definition and the text that follows have been reviewed and approved by the cochairs of the subcommittee and the revised version is published here. The intention is to also seek approval of this definition from the regulatory authorities.
            Article 0 comments Cited 924 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: not found
              • Article: not found

              Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials.

              Christian Ruff, Robert Giugliano, Eugene Braunwald … (2014)
              Four new oral anticoagulants compare favourably with warfarin for stroke prevention in patients with atrial fibrillation; however, the balance between efficacy and safety in subgroups needs better definition. We aimed to assess the relative benefit of new oral anticoagulants in key subgroups, and the effects on important secondary outcomes. We searched Medline from Jan 1, 2009, to Nov 19, 2013, limiting searches to phase 3, randomised trials of patients with atrial fibrillation who were randomised to receive new oral anticoagulants or warfarin, and trials in which both efficacy and safety outcomes were reported. We did a prespecified meta-analysis of all 71,683 participants included in the RE-LY, ROCKET AF, ARISTOTLE, and ENGAGE AF-TIMI 48 trials. The main outcomes were stroke and systemic embolic events, ischaemic stroke, haemorrhagic stroke, all-cause mortality, myocardial infarction, major bleeding, intracranial haemorrhage, and gastrointestinal bleeding. We calculated relative risks (RRs) and 95% CIs for each outcome. We did subgroup analyses to assess whether differences in patient and trial characteristics affected outcomes. We used a random-effects model to compare pooled outcomes and tested for heterogeneity. 42,411 participants received a new oral anticoagulant and 29,272 participants received warfarin. New oral anticoagulants significantly reduced stroke or systemic embolic events by 19% compared with warfarin (RR 0·81, 95% CI 0·73-0·91; p<0·0001), mainly driven by a reduction in haemorrhagic stroke (0·49, 0·38-0·64; p<0·0001). New oral anticoagulants also significantly reduced all-cause mortality (0·90, 0·85-0·95; p=0·0003) and intracranial haemorrhage (0·48, 0·39-0·59; p<0·0001), but increased gastrointestinal bleeding (1·25, 1·01-1·55; p=0·04). We noted no heterogeneity for stroke or systemic embolic events in important subgroups, but there was a greater relative reduction in major bleeding with new oral anticoagulants when the centre-based time in therapeutic range was less than 66% than when it was 66% or more (0·69, 0·59-0·81 vs 0·93, 0·76-1·13; p for interaction 0·022). Low-dose new oral anticoagulant regimens showed similar overall reductions in stroke or systemic embolic events to warfarin (1·03, 0·84-1·27; p=0·74), and a more favourable bleeding profile (0·65, 0·43-1·00; p=0·05), but significantly more ischaemic strokes (1·28, 1·02-1·60; p=0·045). This meta-analysis is the first to include data for all four new oral anticoagulants studied in the pivotal phase 3 clinical trials for stroke prevention or systemic embolic events in patients with atrial fibrillation. New oral anticoagulants had a favourable risk-benefit profile, with significant reductions in stroke, intracranial haemorrhage, and mortality, and with similar major bleeding as for warfarin, but increased gastrointestinal bleeding. The relative efficacy and safety of new oral anticoagulants was consistent across a wide range of patients. Our findings offer clinicians a more comprehensive picture of the new oral anticoagulants as a therapeutic option to reduce the risk of stroke in this patient population. None. Copyright © 2014 Elsevier Ltd. All rights reserved.
              Article 0 comments Cited 841 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Contributors
                Michela Giustozzi:
                ORCID: http://orcid.org/0000-0002-8033-4945
                michelagiustozzi@hotmail.it , michela.giustozzi@unipg.it
                Journal
                Journal ID (nlm-ta): Clin Drug Investig
                Journal ID (iso-abbrev): Clin Drug Investig
                Title: Clinical Drug Investigation
                Publisher: Springer International Publishing (Cham )
                ISSN (Print): 1173-2563
                ISSN (Electronic): 1179-1918
                Publication date (Electronic): 7 December 2020
                Publication date PMC-release: 7 December 2020
                Publication date (Print): 2021
                Volume: 41
                Issue: 1
                Pages: 43-51
                Affiliations
                [1 ]GRID grid.9027.c, ISNI 0000 0004 1757 3630, Internal Vascular and Emergency Medicine and Stroke Unit, , University of Perugia, ; Perugia, Italy
                [2 ]GRID grid.8404.8, ISNI 0000 0004 1757 2304, Internal Medicine of Montevarchi, , University of Florence, ; Florence, Italy
                Author information
                http://orcid.org/0000-0002-8033-4945
                Article
                Publisher ID: 982
                DOI: 10.1007/s40261-020-00982-8
                PMC ID: 7815539
                PubMed ID: 33284370
                SO-VID: 8367c18b-8bac-4c8c-8ca8-66f022f7b917
                Copyright © © The Author(s) 2020
                License:

                Open AccessThis article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.

                History
                Date accepted : 24 October 2020
                Funding
                Funded by: Università degli Studi di Perugia
                Open Access :

                Open access funding provided by Università degli Studi di Perugia within the CRUI-CARE Agreement.

                Categories
                Subject: Original Research Article
                Custom metadata
                issue-copyright-statement © Springer Nature Switzerland AG 2021

                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine
                Data availability:
                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine

                Comments

                Comment on this article

                scite_

                Similar content658

                See all similar

                Cited by8

                See all cited by

                Most referenced authors649

                See all reference authors