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Non-steroidal anti-inflammatory drugs and risk of cerebrovascular events in patients with osteoarthritis: a nested case–control study

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Abstract

Recent studies show that the risk of cardiovascular adverse events for certain traditional non-steroidal anti-inflammatory drugs (NSAIDs) is similar to that of rofecoxib. While these results are focused on ischemic cardiomyopathy, there is little evidence concerning the risk of ischemic stroke/transient ischemic attack and hemorrhagic stroke. Additionally, there is no information on nimesulide and ketoprofen, the most frequently prescribed NSAIDs in Italy, along with diclofenac. This study aims to determine whether the use of NSAIDs is associated with an increased risk of cerebrovascular events in Italy. We performed a case–control analysis nested in a cohort of patients with osteoarthritis between 2002 and 2011 who were newly treated with NSAIDs. The patients were followed until December 31, 2012. Conditional logistic regression was used to estimate odds ratios (ORs) with 95 % confidence intervals (95 % CI) of cerebrovascular events (index date) associated with current (until 30 days before the index date), recent (31–365 days) and past (>365 days) use of NSAIDs. Within a cohort of 29,722 patients, 1566 cases (1546 matched with controls) were identified (incidence rate = 11.0/1000 person–years). The overall rate of cerebrovascular event was not elevated with current NSAIDs overall when compared with past use. Among individual NSAIDs, diclofenac and ketoprofen were the molecules significantly associated with an increased rate of cerebrovascular events (OR = 1.53; 95 % CI 1.04–2.24; OR = 1.62; 95 % CI 1.02–2.58, respectively). The most frequent event was hemorrhagic stroke following the use of ketoprofen (OR = 2.09; 95 % CI 1.05–4.15). Diclofenac and ketoprofen seemed to increase the risk of cerebrovascular events. These findings might influence the choice of NSAIDs according to patient characteristics.

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Acknowledgments

Angelini supported this study but had no role in the design and conduct of the study, the collection, management, analysis, and interpretation of the data, the preparation, review, or approval of the manuscript, or the decision to submit the manuscript for publication.

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Authors and Affiliations

  1. Health Search, Italian College of General Practitioners and Primary Care, Via Sestese 61, 50141, Florence, Italy

    Francesco Lapi, Monica Simonetti, Miriam Levi & Iacopo Cricelli

  2. Pharmacology Unit, Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy

    Carlo Piccinni

  3. Department of Health Sciences, University of Florence, Florence, Italy

    Miriam Levi

  4. Italian College of General Practitioners and Primary Care, Florence, Italy

    Pierangelo Lora Aprile & Claudio Cricelli

  5. Intensive Care Unit, Department of Anesthesia and Postoperative, Istituto Ortopedico Rizzoli, Bologna, Italy

    Andrea Fanelli

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  1. Francesco Lapi
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Correspondence to Francesco Lapi.

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Conflict of interest

F. Lapi and I. Cricelli provided consultations in protocol preparation for epidemiological studies and data analyses for IBSA and Angelini. C. Cricelli and P. A. Lora Aprile provided clinical consultations for IBSA, Angelini, Alfa Wasserman, Pfizer, ProStrakan and Molteni. A. Fanelli provided clinical consultations for Abbivie and IBSA. C. Piccinni, M. Levi and M. Simonetti have no conflicts of interest to disclose.

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Lapi, F., Piccinni, C., Simonetti, M. et al. Non-steroidal anti-inflammatory drugs and risk of cerebrovascular events in patients with osteoarthritis: a nested case–control study. Intern Emerg Med 11, 49–59 (2016). https://doi.org/10.1007/s11739-015-1288-3

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