TY - JOUR
T1 - Risk of ischemic stroke and the use of individual non-steroidal anti-inflammatory drugs
T2 - A multi-country european database study within the SOS Project
AU - Schink, Tania
AU - Kollhorst, Bianca
AU - Lorenzo, Cristina Varas
AU - Arfè, Andrea
AU - Herings, Ron
AU - Lucchi, Silvia
AU - Romio, Silvana
AU - Schade, René
AU - Schuemie, Martijn J.
AU - Straatman, Huub
AU - Valkhoff, Vera
AU - Villa, Marco
AU - Sturkenboom, Miriam
AU - Garbe, Edeltraut
N1 - Funding Information: The research leading to the results of this study has received funding from the European Community’s Seventh Framework Programme under grant agreement number 223495 - the SOS project. The publication of this article was funded by the Open Access Fund of the Leibniz Association. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors want thank all members of the Safety of Nonsteroidal Anti-inflammatory Drugs (SOS) project (http://www.sos-nsaids-project.org/) for their contribution. Publisher Copyright: © 2018 Schink et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2018/9
Y1 - 2018/9
N2 - Background and purpose A multi-country European study using data from six healthcare databases from four countries was performed to evaluate in a large study population (>32 million) the risk of ischemic stroke (IS) associated with individual NSAIDs and to assess the impact of risk factors of IS and co-medication. Methods Case-control study nested in a cohort of new NSAID users. For each case, up to 100 sex- and age-matched controls were selected and confounder-adjusted odds ratios for current use of individual NSAIDs compared to past use calculated. Results 49,170 cases of IS were observed among 4,593,778 new NSAID users. Use of coxibs (odds ratio 1.08, 95%-confidence interval 1.02–1.15) and use of traditional NSAIDs (1.16, 1.12–1.19) were associated with an increased risk of IS. Among 32 individual NSAIDs evaluated, the highest significant risk of IS was observed for ketorolac (1.46, 1.19–1.78), but significantly increased risks (in decreasing order) were also found for diclofenac, indomethacin, rofecoxib, ibuprofen, nimesulide, diclofenac with misoprostol, and piroxicam. IS risk associated with NSAID use was generally higher in persons of younger age, males, and those with a prior history of IS. Conclusions Risk of IS differs between individual NSAIDs and appears to be higher in patients with a prior history of IS or transient ischemic attack (TIA), in younger or male patients. Co-medication with aspirin, other antiplatelets or anticoagulants might mitigate this risk. The small to moderate observed risk increase (by 13–46%) associated with NSAIDs use represents a public health concern due to widespread NSAID usage.
AB - Background and purpose A multi-country European study using data from six healthcare databases from four countries was performed to evaluate in a large study population (>32 million) the risk of ischemic stroke (IS) associated with individual NSAIDs and to assess the impact of risk factors of IS and co-medication. Methods Case-control study nested in a cohort of new NSAID users. For each case, up to 100 sex- and age-matched controls were selected and confounder-adjusted odds ratios for current use of individual NSAIDs compared to past use calculated. Results 49,170 cases of IS were observed among 4,593,778 new NSAID users. Use of coxibs (odds ratio 1.08, 95%-confidence interval 1.02–1.15) and use of traditional NSAIDs (1.16, 1.12–1.19) were associated with an increased risk of IS. Among 32 individual NSAIDs evaluated, the highest significant risk of IS was observed for ketorolac (1.46, 1.19–1.78), but significantly increased risks (in decreasing order) were also found for diclofenac, indomethacin, rofecoxib, ibuprofen, nimesulide, diclofenac with misoprostol, and piroxicam. IS risk associated with NSAID use was generally higher in persons of younger age, males, and those with a prior history of IS. Conclusions Risk of IS differs between individual NSAIDs and appears to be higher in patients with a prior history of IS or transient ischemic attack (TIA), in younger or male patients. Co-medication with aspirin, other antiplatelets or anticoagulants might mitigate this risk. The small to moderate observed risk increase (by 13–46%) associated with NSAIDs use represents a public health concern due to widespread NSAID usage.
UR - http://www.scopus.com/inward/record.url?scp=85053632920&partnerID=8YFLogxK
U2 - https://doi.org/10.1371/journal.pone.0203362
DO - https://doi.org/10.1371/journal.pone.0203362
M3 - Article
C2 - 30231067
SN - 1932-6203
VL - 13
JO - PLOS ONE
JF - PLOS ONE
IS - 9
M1 - e0203362
ER -