Increased Risk of Stroke Associated With Nonsteroidal Anti-Inflammatory Drugs A Nationwide Case-Crossover Study

ArticleinStroke 41(9):1884-90 · September 2010with18 Reads
DOI: 10.1161/STROKEAHA.110.585828 · Source: PubMed
Abstract
Limited studies assessed cerebrovascular safety of individual nonsteroidal anti-inflammatory drugs (NSAIDs). We evaluated the risk of ischemic and hemorrhagic stroke associated with short-term use of selective and nonselective NSAIDs in a Chinese population with a high incidence of stroke. A retrospective case-crossover study was conducted by analyzing the Taiwan National Health Insurance Database. We identified all ischemic and hemorrhagic stroke patients in 2006, aged >or=20 years, based on International Classification of Diseases, 9th Revision, Clinical Modification diagnosis codes from inpatient claims and defined the index date as the date of hospitalization. For each patient, we defined case period as 1 to 30 days before the index date and control period as 91 to 120 days before the index date. A pharmacy prescription database was searched for NSAID use during the case and control periods. We calculated adjusted ORs and their 95% CIs with a conditional logistic regression model. A total of 28 424 patients with ischemic stroke and 9456 patients with hemorrhagic stroke were included. For ischemic stroke, a modest increased risk was evident for all oral NSAIDs with adjusted ORs (95% CI) ranging from 1.20 (1.00 to 1.44) for celecoxib to 1.90 (1.39 to 2.60) for ketorolac. For hemorrhagic stroke, oral ketorolac was associated with a significantly higher risk with OR of 2.69 (1.56 to 4.66). Significantly increased risk was found for parenteral NSAIDs, in particular ketorolac, with an OR of 3.92 (3.25 to 4.72) for ischemic stroke and 5.98 (4.40 to 8.13) for hemorrhagic stroke. Use of selective and nonselective NSAIDs was associated with an increased risk of both ischemic and hemorrhagic stroke, strikingly high for parenteral ketorolac.
    • "However, the results of large scale clinical testing in Alzheimer's disease patients have indicated that contrary to the expectations NSAIDs had an adverse rather than a beneficial effect [3]. Furthermore, clinical studies have shown that NSAID use is associated with a higher risk for stroke [4]. Large scale studies of NSAID use by healthy individuals have uncovered significantly elevated incidence of cardiovascular events and stroke [5]. "
    [Show abstract] [Hide abstract] ABSTRACT: Non-steroidal anti-inflammatory drugs such as indomethacin are widely used to treat inflammatory diseases and manage pain, fever and inflammation in several conditions, including neuropsychiatric disorders. Although they predominantly function by inhibiting cyclooxygenase (COX) activity, important COX-independent actions also occur. These actions could be responsible for the adverse side effects associated with chronic and/or high dose usage of this popular drug class. We examined gene regulation in the hippocampus after peripheral administration of indomethacin by employing a microarray approach. Secondary confirmation and the brain expression pattern of regulated genes was examined by in situ hybridization and immunohistochemistry. Transglutaminase 2, serum glucocorticoid inducible kinase, Inhibitor of NF-kappa B and vascular endothelial growth factor were among genes that were prominently upregulated, while G-protein coupled receptor 56 and neuropeptide Y were among genes that were downregulated by indomethacin. Co-localization studies using blood vessel markers revealed that transglutaminase 2 was induced specifically in brain vasculature. The data demonstrate that COX-inhibitors can differentially regulate gene transcription in multiple, functionally distinctly cell types in the brain. The results provide additional insight into the molecular actions of COX-inhibitors and indicate that their effects on vasculature could influence cerebral blood flow mechanisms.
    Full-text · Article · Oct 2015
    • "Therefore, it is not surprising that heart failure clinical guidelines [25] discourage NSAID use in these patients. Stroke incidence does not seem to be increased with NSAID use in most studies, although some specific populations might be at risk as suggested [26] in a Chinese study. Similarly, an association of NSAID use with atrial fibrillation has been postulated but not demonstrated [27]. "
    [Show abstract] [Hide abstract] ABSTRACT: Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most frequently used medications. NSAIDs profoundly modify prostaglandin homeostasis through inhibition of the enzyme, cyclooxygenase (COX), especially COX-2. COX-2 inhibition is associated with adverse cardiovascular outcomes as demonstrated by recent trials using this type of drug. This review explores the latest available data, including recent, randomized, clinical trials, controversies, and pathophysiology of the adverse effects of COX-inhibition. Copyright © 2015 Elsevier Inc. All rights reserved.
    Article · Mar 2015
    • "We found 13 eligible studies with information on the concomitant ASA (Biere-Rafi et al. 2011; Chang et al. 2010; Garcia Rodriguez et al. 2008; Huerta et al. 2005; Lafrance and Miller 2012; Lapeyre-Mestre et al. 2013; Layton et al. 2003a, b; Mangoni et al. 2010a, b; Schneider et al. 2006; van Staa et al. 2008; Varga et al. 2013) (Table 4). In general, the use of ASA resulted in the widening of the 95 % CI around the calculated composite CV/renal risk estimates. "
    [Show abstract] [Hide abstract] ABSTRACT: Non-steroidal anti-inflammatory drugs (NSAIDs) are known to increase the risk of cardiovascular (CV) and renal incidences, especially at higher doses and upon long term use. However, the available reports are criticized for lack of specificity, grouping of vastly different outcomes together and ignoring the heterogeneity among NSAIDs. In this systematic review, we are reporting CV/renal risks associated with meloxicam, stratified into myocardial, vascular, renal risk categories, to address the differential nature of NSAIDs effects on different body systems. We are also reporting composite CV/renal risk to present overall risk associated with various covariates. We searched the online healthcare databases for observational studies or randomized controlled trials, reporting myocardial or all-cause mortality outcome (>90 days exposure) and/or vascular/renal outcomes (any exposure) after meloxicam use, published until April 2014. The combined odd ratio values (OR'; 95 % CI) were calculated using the random effect inverse variance model. We found 19 eligible studies out of 2,422 reports. Meloxicam demonstrated a low increase in composite risk (OR' 1.14; CI 1.04-1.25) which was mainly vascular in nature (OR' 1.35; CI 1.18-1.55] as it did not elevate myocardial (OR' 1.13; CI 0.98-1.32) or renal (OR', 0.99; CI 0.72-1.35) risks. Relative to meloxicam, other NSAIDs increased the composite risk, in a dose-dependent fashion, in the following order: rofecoxib > indomethacin > diclofenac > celecoxib > naproxen > ibuprofen. OR' was also influenced by type of disease and the comparator used, and acetylsalicylic acid. NSAIDs are heterogeneous in increasing CV/renal risks. The low increased risk associated with meloxicam is mainly vascular in origin.
    Full-text · Article · Dec 2014
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