Morten Lamberts, MD, PhD; Gregory Y.H. Lip, MD *; Morten Lock Hansen, MD, PhD; Jesper Lindhardsen, MD, PhD; Jonas Bjerring Olesen, MD, PhD; Jakob Raunsø, MD, PhD; Anne-Marie Schjerning Olsen, MD, PhD; Per Kragh Andersen, PhD, DMSc; Thomas Alexander Gerds, Dr Rer Nat; Emil L. Fosbøl, MD, PhD; Christian Torp-Pedersen, MD, DMSc *; Gunnar H. Gislason, MD, PhD *
Financial Support: Dr. Gislason is supported by an unrestricted research scholarship from the Novo Nordisk Foundation.
Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M13-1581.
Reproducible Research Statement:Study protocol: Not applicable. Statistical code: Methods for calculation of absolute risk are available from Dr. Lamberts (e-mail, firstname.lastname@example.org). Data set: Raw data are available from Statistics Denmark (www.dst.dk/en.aspx).
Requests for Single Reprints: Morten Lamberts, MD, PhD, Department of Cardiology, Gentofte University Hospital, Post 635, Niels Andersens Vej 65, 2900 Hellerup, Denmark; e-mail, email@example.com.
Current Author Addresses: Drs. Lamberts, Hansen, Lindhardsen, Olesen, Raunsø, Olsen, Fosbøl, and Gislason: Department of Cardiology, Gentofte University Hospital, Post 635, Niels Andersens Vej 65, 2900 Hellerup, Denmark.
Dr. Lip: Department of Medicine, City Hospital, University of Birmingham, Dudley Road, Birmingham B18 7QH, United Kingdom.
Dr. Andersen: University of Copenhagen, Oster Farimagsgade 5, Postboks 2099, 1014 Copenhagen, Denmark.
Dr. Gerds: Department of Public Health, Section of Biostatistics, University of Copenhagen, Oster Farimagsgade 5, Postboks 2099, Room 15-2-07, 1014 Copenhagen, Denmark.
Dr. Torp-Pedersen: Department of Health Science and Technology, Aalborg University, Niels Jernesvej 12, A5-208, 9220 Aalborg, Denmark.
Author Contributions: Conception and design: M. Lamberts, G.Y.H. Lip, M.L. Hansen, A.M.S. Olsen, E.L. Fosbøl, G.H. Gislason.
Analysis and interpretation of the data: M. Lamberts, G.Y.H. Lip, J. Lindhardsen, J.B. Olesen, J. Raunsø, A.M.S. Olsen, P.K. Andersen, T.A. Gerds, E.L. Fosbøl, G.H. Gislason.
Drafting of the article: M. Lamberts, G.Y.H. Lip, J. Lindhardsen, J. Raunsø, P.K. Andersen.
Critical revision of the article for important intellectual content: M. Lamberts, G.Y.H. Lip, M.L. Hansen, J. Lindhardsen, J.B. Olesen, J. Raunsø, A.M.S. Olsen, P.K. Andersen, E.L. Fosbøl, C. Torp-Pedersen, G.H. Gislason.
Final approval of the article: M. Lamberts, G.Y.H. Lip, J. Lindhardsen, J.B. Olesen, J. Raunsø, A.M.S. Olsen, P.K. Andersen, E.L. Fosbøl, G.H. Gislason.
Statistical expertise: J. Lindhardsen, P.K. Andersen, T.A. Gerds, G.H. Gislason.
Obtaining of funding: G.H. Gislason.
Administrative, technical, or logistic support: J. Lindhardsen, G.H. Gislason.
Collection and assembly of data: M. Lamberts, J. Lindhardsen, C. Torp-Pedersen, G.H. Gislason.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are assumed to increase bleeding risk, but their actual relation to serious bleeding in patients with atrial fibrillation (AF) who are receiving antithrombotic medication is unknown.
To investigate the risk for serious bleeding and thromboembolism associated with ongoing NSAID and antithrombotic therapy.
Observational cohort study.
Danish patients with AF hospitalized between 1997 and 2011.
Absolute risk for serious bleeding and thromboembolism with ongoing NSAID and antithrombotic therapy, assessed by using Cox models.
Of 150 900 patients with AF (median age, 75 years [interquartile range, 65 to 83 years]; 47% female), 53 732 (35.6%) were prescribed an NSAID during a median follow-up of 6.2 years (interquartile range, 2.1 to 14.0 years). There were 17 187 (11.4%) and 19 561 (13.0%) occurrences of serious bleeding and thromboembolism, respectively. At 3 months, the absolute risk for serious bleeding within 14 days of NSAID exposure was 3.5 events per 1000 patients compared with 1.5 events per 1000 patients without NSAID exposure. The risk difference was 1.9 events per 1000 patients. In patients selected for oral anticoagulant therapy, the absolute risk difference was 2.5 events per 1000 patients. Use of NSAIDs was associated with increased absolute risks for serious bleeding and thromboembolism across all antithrombotic regimens and NSAID types. An NSAID dosage above the recommended minimum was associated with a substantially increased hazard ratio for bleeding.
Observational design and unmeasured confounders.
Use of NSAIDs was associated with an independent risk for serious bleeding and thromboembolism in patients with AF. Short-term NSAID exposure was associated with increased bleeding risk. Physicians should exercise caution with NSAIDs in patients with AF.
Lamberts M, Lip GY, Hansen ML, Lindhardsen J, Olesen JB, Raunsø J, et al. Relation of Nonsteroidal Anti-inflammatory Drugs to Serious Bleeding and Thromboembolism Risk in Patients With Atrial Fibrillation Receiving Antithrombotic Therapy: A Nationwide Cohort Study. Ann Intern Med. ;161:690–698. doi: 10.7326/M13-1581
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Published: Ann Intern Med. 2014;161(10):690-698.
Cardiology, Hematology/Oncology, Rhythm Disorders and Devices.
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