Impact Of Non-steroidal Anti-inflammatory Drugs Research Articles

Selective COX-2 Inhibitor (Meloxicam) and Tooth-Supporting Bone Quality. A Histomorphometric Study in Rats.

The effects of the non-steroidal anti-inflammatory drugs (NSAIDs) on bone quantity and quality were investigated for years. However, there is lack of information on the impact of NSAIDs on the quality of tooth-supporting alveolar bone in absence of periodontal inflammation. Thus, the aim of this study was to evaluate histometrically the influence of a selective COX-2 NSAID (Meloxicam) on the inter-radicular bone mineral density in rats. Forty-nine adult male Wistar rats were randomly divided into four experimental groups: Subcutaneous injection of 0.9% sterile saline for 15 days (G1; n=12) and 45 days (G2; n=11); and subcutaneous injection of Meloxicam for 15 days (G3; n=13) and 45 days (G4; n=13). Mineral density was histometrically determined in the inter-radicular area of the 1st mandibular molars and data analysis performed by two-way ANOVA (a=5%). Results showed no interaction between time and treatment (p>0.05) and that meloxicam did not affect the alveolar bone density. In contrast, it was found that inter-radicular alveolar bone density increased with time (91.88±3.08% and 92.86±2.38% for groups 15 and 45 days, respectively) (p<0.05). Within the limits of this study, daily administration of a selective COX-2 inhibitor (Meloxicam) did not affect the quality of the inter-radicular alveolar bone in absence of periodontal infection.

P208 - The impact of non-steroidal anti-inflammatory drugs (NSAIDs) on breast cancer recurrence

P208 - The impact of non-steroidal anti-inflammatory drugs (NSAIDs) on breast cancer recurrence

Gene response of CYP360A, CYP314, and GST and whole-organism changes in Daphnia magna exposed to ibuprofen

The fate and ecological impact of non-steroidal anti-inflammatory drugs (NSAIDs) in aquatic environments has gained increasingly concern recently. However, limited information is provided about the toxicity mechanism of NSAIDs to aquatic invertebrates. In the present study, we investigated the expression of CYP360A, CYP314, and GST genes involved in the detoxification process and the responses of their associated enzymes activity, as well as whole-organism changes in Daphnia magna exposed to environmentally relevant concentrations of ibuprofen (IBU). Results showed that the total amount of eggs produced per female, total number of brood per female, and body length were significantly decreased under IBU exposure, suggesting the effects of chronic IBU exposure on growth and reproduction of D. magna cannot be ignored. In gene expression level, the CYP360A gene, homologue to CYP3A in mammalian, showed inhibition at low concentration of IBU (0.5μg·L−1) and induction at high concentration of IBU (50μg·L−1). GST gene also exhibited a similar performance to CYP3A. CYP314 displayed inhibition for short time exposure (6h) and induced with prolonged exposure time (48h) at low concentration of IBU (0.5μg·L−1). Erythromycin N-demethylase (ERND) and aminopyrine N-demethylase (APND) related to cytochrome oxidase P450 (CYPs) were inhibited for short time exposure (6h) to IBU and then activated with prolonged exposure time (48h) at low concentration of IBU (0.5μg·L−1), while EROD showed a dose-dependent pattern under IBU exposure. As for antioxidative system, induction of glutathione S-transferase (GST), superoxide dismutase (SOD), and catalase (CAT) was observed in short-term exposure to IBU. Meanwhile, methane dicarboxylic aldehyde (MDA) content increased with the increasing IBU concentration and the delayed exposure time, displaying obvious dose- and time-dependent pattern. In summary, IBU significantly altered some physiological and biochemical parameters and genes expressions associated with detoxification metabolism in D. magna, the integrated approach combining the response in molecule levels with the performance of the whole organism can help elucidate the toxic effects of IBU and provide more insight into the exact mechanism of toxicity in aquatic organisms.

Cervicofacial cellulitis: The impact of non-steroidal anti-inflammatory drugs. A study of 70 cases

IntroductionCervicofacial cellulitis (CFC) is a severe infection of the subcutaneous cellular tissue, and is one of the most serious head and neck infectious emergencies. In a series of 70 cases treated between 2007 and 2012, we noticed a strong correlation between use of non-steroidal anti-inflammatory drugs (NSAIDs) and evolution of head and neck infections toward CFC, including two cases of necrotic CFC extending to the mediastinum, which were fatal. Material and methodsThe cases included in the series comprised patients admitted to emergency and requiring hospitalization due to the severity of presenting symptoms. There were 70 such cases of CFC between 2007 and 2012; cases managed on an outpatient basis were excluded, as were cases of orbital CFC, CFC of sinus origin and mastoiditis. ResultsEighty percent of patients took NSAIDs, on self-medication or by prescription (community physician, dentist, pharmacist). The most frequent molecules were tiaprofenic acid and diclofenac. CFC extension was restricted in most cases to the maxillary and/or ipsilateral subhyoid region, with 5 cases of lower cervical extension and 2 of mediastinal involvement, which both proved fatal. ConclusionCFC is a severe infection that can be life-threatening, and represents a diagnostic and therapeutic emergency. Among other risk factors, use of NSAIDs is frequently reported; these should therefore be used with caution if at all in head and neck infection, especially of odonto-stomatological origin.

The efficacy and safety of non-steroidal anti-inflammatory drugs in preventing the recurrence of colorectal adenoma: a meta-analysis and systematic review of randomized trials.

We report a meta-analysis and systematic review of randomized trials assessing the impact of non-steroidal anti-inflammatory drugs (NSAIDs) in preventing recurrence of colorectal adenoma. PubMed/Medicine, EMBASE and the Cochrane Central Register of Controlled Trials databases were searched for relevant randomized double-blind placebo-controlled trials published before March 2014. Two authors independently assessed study quality and extracted data. stata software was used to investigate heterogeneity between studies, and analysis was performed using a fixed-effects model to calculate and merge data. Nine studies, with 8521 subjects, were included. Results were categorized by the duration of follow-up. The relative risks of any recurrence of adenoma in patients receiving NSAIDs compared with the placebo group were 0.68 [95% confidence interval (CI) 0.63-0.73, P=0.001] for patients with a 1-year follow-up, 0.75 (95% CI 0.68-0.83, P=0.246) with 3years and 1.43 (95% CI 1.14-1.79, P=0.127) with follow-up of over 3years. Using pooled risk ratios, NSAIDs were associated with a significant decrease in adenoma recurrence at 1 and 3years, although this association was lost beyond 3years of follow-up. For secondary prevention of advanced adenomas, the pooled risk ratios (compared with placebo) were 0.51 (95% CI 0.43-0.60, P=0.026) after 1year, 0.61 (95% CI 0.50-0.76, P=0.887) at 3years and 1.39 (95% CI 0.89-2.16, P=0.829) after 3years. The meta-analysis indicated that oral NSAIDs may be effective in the early prevention of secondary occurrence of adenomas.

Impact of nonaspirin nonsteroidal anti-inflammatory agents and acetaminophen on sensorineural hearing loss: a systematic review.

To perform a systematic review evaluating the association between sensorineural hearing loss and (1) nonsteroidal anti-inflammatory drugs (NSAIDs) as a class, (2) NSAIDs available over the counter, (3) NSAIDs in short intravenous courses, (4) prescription NSAIDs utilized by patients without systemic inflammatory conditions, (5) prescription NSAIDs in patients with arthritides, and (6) acetaminophen with and without concomitant narcotic usage. Computerized searches of PubMed, EMBASE, and the Cochrane Library were updated through May 2014, along with manual searches and inquiries to topic experts. The systematic review was performed according to an a priori protocol. Data extraction was performed by 2 independent investigators, and it focused on relevant audiologic measurements, methodological elements related to risk of bias, and potential confounders. The 23 criterion-meeting studies included a total of 92,532 participants, with mixed results. Sulindac was the only specific agent to have been studied with formal audiometry in a randomized double-blind placebo-controlled trial in which hearing was the reported primary outcome: Although an effect was seen in the unadjusted analysis (pure tone threshold>15 dB, 9.3% vs 2.9%; relative risk [RR], 3.2; confidence interval [CI], 1.09-9.55; P=.02), the effect dissipated in the adjusted analysis (P=.09). There was a significant effect on self-reported hearing loss from NSAIDs as a class (RR, 1.21; CI, 1.11-1.33), ibuprofen (RR, 1.13; CI, 1.06-1.19), and acetaminophen (RR, 1.21; CI, 1.11-1.33), but no formal audiometric data confirm or refute this suggested effect. Audiometry has demonstrated profound loss in some instances of acetaminophen-narcotic combination ingestions. Data are varied regarding the impact of NSAIDs and acetaminophen on population hearing health.

Impact of non-steroidal anti-inflammatory drugs on hypertensive disorders of pregnancy

Non-steroidal anti-inflammatory drug (NSAID) use has the potential to adversely affect blood pressure in women with hypertensive disorders of pregnancy. We sought to evaluate this association. Women affected with severe hypertensive disorders of pregnancy were identified by retrospective chart review. The medication administration record was then used to identify controls (no NSAID exposure) until a sufficient number of patients were obtained, after which the cases (NSAID exposed) were identified in a chronological manner during the same study period until a 2:1 ratio was achieved. The primary outcome was the change in mean of all postpartum mean arterial pressures (MAP) throughout the hospital stay. Power analysis showed that 146 exposed and 73 unexposed subjects were necessary to obtain 90% power to detect a MAP difference of 10mmHg between the groups. Secondary outcomes included: initiation of anti-hypertensive medication, need for increased doses of anti-hypertension medication, and adverse events related to hypertension. 223 women had severe hypertensive disorders of pregnancy, of whom 75 (34%) were not exposed to NSAIDs and 148 (66%) were exposed. NSAID exposure was not associated with a difference in the average MAP postpartum (p=0.70), nor any of the secondary outcomes evaluated. Exposure to NSAIDs was less likely as serum creatinine increased (p=0.012). In women with severe hypertensive disorders of pregnancy, NSAIDs did not appear to increase the average postpartum MAP, increase the requirement for anti-hypertensive medications, or increase the rate of adverse postpartum events.

The impact of diclofenac and ibuprofen on biofilm formation on the surface of polypropylene mesh

PurposeThe difficulties related to treatment of deep surgical site infection involve formation of biofilm on the surface of synthetic material. It is considered that in treatment of infections involving formation of biofilm, concomitant therapy shall be applied covering anti-inflammatory drugs. The purpose of the work was to assess the impact of diclofenac and ibuprofen on bacterial biofilm formation on the surface of monofilament polypropylene mesh.Materials and methodsThe study involved 70 strains of Staphylococcus aureus and 70 strains of Escherichia coli isolated from different patients and those which differ with chromosomal DNA pattern within the species. The assessment of the impact of non-steroidal anti-inflammatory drugs (NSAIDs) on biofilm formation was carried out with the use of qualitative method (TTC reduction), quantitative (tenfold serial dilution) and with the use of scanning electron microscope (SEM).ResultsIn the qualitative assessment, after incubation in the medium containing NSAIDs statistically significant growth of S. aureus strain amount and E. coli which poorly make up biofilm was stated. Quantitative examination indicated characteristic decrease of the number of colony forming units in 1 ml of the suspension isolated from bacterial biofilm formed as a result of incubation of isolates in the medium with the addition of examined NSAIDs in comparison to biofilm from control regimen. In the examination with the use of SEM it was stated that the effect of isolates incubation in the medium with NSAIDs was decrease of the number of bacteria adjacent to the biomaterial surface.ConclusionsDiclofenac and ibuprofen in the concentration obtained in the serum limit the formation of biofilm by S. aureus and E. coli.

The impact of non-steroidal anti-inflammatory drugs on the small intestinal epithelium

The small intestine has been called as a dark continent of digestive tract and it had been very difficult to diagnose or treat the disease of small intestine. However recent technological development including video capsule endoscopy or balloon-assisted endoscopy has made us to aware the various diseases of small intestine. By using capsule endoscopy, many researchers reported that more than 70% of patients treated continuously with non-steroidal anti-inflammatory drugs (NSAID) exhibit the mucosal damage of small intestine. In some cases, NSAID not only causes mucosal damage but also results in life threatening bleeding from small intestine, which had not been prevented or cured by gastro-protective drug or anti-gastric acid secretion drug administration. Therefore to investigate and identify the effective drug that protects small intestine from mucosal damage is urgently expected. In spite of extensive investigation in clinical field, only a few drugs such as misoprostol, a synthetic prostaglandin E1 analogue, has been reported as an effective one but is not satisfactory enough to fulfill the requirement of patients who suffer from NSAID-induced mucosal damage of small intestine. And now, extensive study is being performed using several gastro-mucoprotective drugs by many researchers. In this review, we introduce the current clinical situation in small intestinal injury of patients under NSAID treatment, and to summarize the molecular mechanism by which NSAID, including acetyl salicylic acid, cause small intestinal damage. In addition, we present results of clinical trials performed so far, and refer the possible preventive method or treatment in the near future.

The Impact of Nonsteroidal Anti-inflammatory Drugs on Inflammatory Response After Aneurysmal Subarachnoid Hemorrhage

The degree of inflammatory response with cytokine release is associated with poor outcomes after aneurysmal subarachnoid hemorrhage (SAH). Previously, we reported on an association between systemic IL-6 levels and clinical outcome in patients with aneurysmal SAH. The intention was to assess the impact of nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen on the inflammatory response after SAH. Our method involved exploratory analysis of data and samples collected within a previous study. In 138 patients with SAH, systemic interleukin (IL-6) and c-reactive protein (CRP) were measured daily up to day 14 after SAH. The correlations among the cumulatively applied amount of NSAIDs, inflammatory parameters, and clinical outcome were calculated. An inverse correlation between cumulatively applied NSAIDs and both IL-6 and CRP levels was found (r = -0.437, p < 0.001 and r = -0.369, p < 0.001 respectively). Multivariable linear regression analysis showed a cumulative amount of NSAIDs to be independently predictive for systemic IL-6 and CRP levels. The cumulative amount of NSAIDs reduced the odds for unfavorable outcome, defined as Glasgow outcome scale 1-3. The results indicate a potential beneficial effect of NSAIDs in patients with SAH in terms of ameliorating inflammatory response, which might have an impact on outcome.

Impact of non-steroidal anti-inflammatory drugs on gastrointestinal cancers: Current state-of-the science

Growing evidence from epidemiologic and preclinical studies suggests that nonsteroidal anti-inflammatory drugs (NSAIDs) reduce the risk of gastrointestinal (GI) cancers, including esophageal, gastric, pancreatic, colorectal cancer, and hepatocellular carcinoma. However, there is also evidence indicating the absence of this benefit. The exact mechanism of NSAIDs’ action on GI tumors is not known. Although some studies have suggested inhibition of carcinogenesis by NSAIDs through suppression effect on inflammation-associated cyclooxygenase-2 (COX-2) expression, other studies have suggested COX-2-independent mechanisms. Herein, we summarize the current state of-the-science regarding NSAID benefit for patients with GI cancers.

Aspirin is associated with lower melanoma risk among postmenopausal Caucasian women

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with decreased risk of gastric, colorectal, and breast cancer. However, the impact of NSAIDs on the risk of melanoma has been inconsistent. The authors evaluated the association between NSAID use and cutaneous melanoma risk in the Women's Health Initiative (WHI) Observational Study (OS). At study entry, use of aspirin (acetylsalicylic acid [ASA]) and nonaspirin NSAIDs was assessed among 59,806 postmenopausal Caucasian women ages 50 to 79 years. Cox proportional hazards models were constructed after adjusting for participant skin type, sun exposure history, and medical indications for NSAID use among other confounders. During a median follow-up of 12 years, 548 incident melanomas were confirmed by medical review. Women who used ASA had a 21% lower risk of melanoma (hazard ratio, 0.79; 95% confidence interval, 0.63-0.98) relative to nonusers. Increased duration of ASA use (<1 year, 1-4 years, and ≥ 5 years) was associated with an 11% lower risk of melanoma for each categorical increase (Ptrend = .01), and women with ≥ 5 years of use had a 30% lower melanoma risk (hazard ratio, 0.70; 95% confidence interval, 0.55-0.94). In contrast, use of non-ASA NSAIDs and acetaminophen were not associated with melanoma risk. Postmenopausal women who used ASA had a significantly lower risk of melanoma, and longer duration of ASA use was associated with greater protection. Although this study was limited by the observational design and self-report of NSAID use, the findings suggest that ASA may have a chemopreventive effect against the development of melanoma and warrant further clinical investigation.

Impact of NSAIDs on cardiovascular risk and hypertension

Introduction: In recent years, there has been a great deal of evaluation of the cardiovascular (CV) effects of the non-steroidal anti-inflammatory drugs (NSAIDs) and the selective cyclooxygenase- 2 (COX-2) inhibitors. Materials and methods: In this brief review, the focus is on both effects of the NSAIDs and COX-2 inhibitors on blood pressure and CV events. The literature was searched using PubMed for both clinical trials and observational studies reviewing the relations among NSAIDs, blood pressure, and CV events. Results: Clinical trial results for NSAIDs and COX-2 inhibitors have shown varying levels of destabilization of blood pressure control in treated hypertensive patients as well as variable incident rates of the development of arrhythmias, congestive heart failure, myocardial infarction, and stroke. Discussion: The non-selective and COX-2 selective NSAIDs can be used with care in selected arthritis patients with hypertension and stable CV disorders (excluding congestive heart failure and moderate to severe kidney dysfunction) when the individual clinical benefit of antiinflammatory therapy outweighs the CV and gastrointestinal risk.

Research progress of the nonsteroidal anti-inflammatory drugs on colorectal anastomotic healing

Background Non-steroidal anti-inflammatory drugs (NSAIDs) are a class of drugs with effects of antiinflammatory,analgesic and antipyretic.It is main by the way of blocking arachidonic acid synthesis of prostaglandins by inhibiting epoxide hydrolase to achieve the effects of antipyretic,analgesic and anti-inflammatory.In recent years,use of NSAIDS with narcotic drugs for perioperative analgesia achieved good clinical result,it particularly widely used in post-operative analgesia.Objective Anastomotic leakage is one of the most serious complications in colorectal surgery.The reports about whether NSAIDs affect colorectal anastomotic healing and increase the incidence of anastomotic leak are different.Content This review summarizes representative literature NSAIDs colorectal anastomotic healing in humans and experimental animals in recent years.Trend This review provides a reference for the safe use of NSAIDs and summarizs the impact of NSAIDs on colorectal anastomotic healing mechanism. Key words: Non-steroidal anti-inflammatory drugs; Colorectal anastomosis; Anastomosis leakage; Heal

Non-steroidal anti-inflammatory drugs (NSAIDs) and hypertension treatment intensification: a population-based cohort study

Non-steroidal anti-inflammatory drugs (NSAIDs) are known to antagonize the effects of antihypertensive drugs, and these associations can lead to an increase in arterial blood pressure. However, the impact of NSAIDs on hypertension treatment management in large-scale populations remains poorly evaluated. We examined whether the introduction of NSAID into the treatment regimen would induce an intensification of hypertension treatment (defined as the introduction of a new antihypertensive drug). We conducted a cohort study involving 5,710 hypertensive subjects included in the French health insurance system database who had been treated and stabilized with their antihypertensive therapy and not exposed to any NSAID between 1 April 2005 and 1 April 2006. The maximum follow-up duration was 4 years. Adjusted hazard ratios (HR) for hypertension treatment intensification were 1.34 [95 % confidence interval (CI) 1.05-1.71] for NSAIDs in general, 1.79 (95 % CI 1.15-2.78) for diclofenac and 2.02 (95 % CI:1.09-3.77) for piroxicam. There were significant interactions between NSAIDs and angiotensin converting enzyme inhibitors (ACEIs; HR 4.09, 95 % CI 2.02-8.27) or angiotensin receptor blockers (ARBs; HR 3.62, 95 % CI 1.80-7.31), but not with other antihypertensive drugs. Exposure to NSAIDs leads to an intensification of hypertension treatment, especially in patients treated with ACEIs or ARBs. Renin-angiotensin system blockers should be avoided whenever NSAIDs are prescribed.

Using non-steroidal anti-inflammatory drugs around calving: Maximizing comfort, productivity and fertility

Non-steroidal anti-inflammatory drugs (NSAIDs) have analgesic, anti-inflammatory, anti-endotoxic and anti-pyretic effects in cattle. As such, they could be expected to have significant effects in cows and calves in the post-calving period. This review evaluates the published data on the use of NSAIDs in the dam and its calf after dystocia, the impact of NSAIDs on uterine involution, the restoration of ovarian function and prevention and treatment of the metritis complex, and the benefits of using NSAIDs in the recumbent cow. Overall, the published data are very limited, despite frequent use of NSAIDs by veterinarians in the post-calving cow, and the small number of published studies focus on blanket treatment of calving cows rather than targeted treatment after dystocia. Blanket treatment had no economic benefit; indeed, some studies reported adverse effects, such as pyrexia and increased risk of metritis. There is even less information on the value of treating calves with NSAIDs after dystocia, despite significant tissue damage which may benefit from NSAID use. Appreciably more studies have evaluated the influence of NSAIDs on uterine and ovarian function, but clinical relevance is limited. In cows with a normal puerperium, prolonged treatment with NSAIDs may slow the restoration of normal function, but most reported studies are small and use NSAIDs more frequently and for longer periods than is common in general practice. The evidence of a clinical benefit in cows with puerperal disease is limited and equivocal, and the evidence base for the use of NSAIDs in the treatment of recumbent cows is also small, even though an expert panel concluded that NSAIDs were a key aspect of veterinary treatment of downer cows. The lack of evidence identified by this review supports the contention that NSAIDs are likely to be under-used and sub-optimally prescribed in the post calving period. Further research on the use of NSAIDs in the post-calving cow and calf is required.

Use of Nonsteroidal Anti-inflammatory Drugs and Survival Following Breast Cancer Diagnosis

While there is accumulating evidence that use of nonsteroidal anti-inflammatory drugs (NSAID) decreases breast cancer risk, little is known about the impact of NSAIDs on survival after breast cancer diagnosis. We assessed whether recent, prediagnostic NSAID use and lifetime cumulative aspirin use before diagnosis were associated with survival among 1,024 women with incident, primary, invasive breast cancer. Recent prediagnostic use of aspirin, ibuprofen, and acetaminophen and lifetime use of aspirin up to diagnosis were not associated with either all-cause mortality or breast cancer-specific mortality. Neither dose nor frequency of use was associated with risk. Associations were not different for pre- and postmenopausal women. In our data, prediagnostic NSAID use and lifetime cumulative aspirin use were not associated with breast cancer survival. Our findings do not support a role of NSAIDs prior to diagnosis in breast cancer survival.

Letter by Naimer Regarding Article, “Duration of Treatment With Nonsteroidal Anti-Inflammatory Drugs and Impact on Risk of Death and Recurrent Myocardial Infarction in Patients With Prior Myocardial Infarction: A Nationwide Cohort Study”

To the Editor: I read with great interest the article by Schjerning Olsen et al,1 in which they demonstrated the apparent detrimental impact of nonsteroidal anti-inflammatory drugs on the incidence of cardiac events in patients with a previous infarct. Although an abundance of evidence confirms the harmful influence of the class effect of cyclooxygenase inhibitors on cardiac function and coronary vascularity, the authors assert further epidemiological support that short-term treatment too can have dangerous implications. However, the authors' methods overlooked the …

Impact of NSAIDs on cardiovascular risk and hypertension

In recent years, there has been a great deal of evaluation of the cardiovascular (CV) effects of the non-steroidal anti-inflammatory drugs (NSAIDs) and the selective cyclooxygenase-2 (COX-2) inhibitors. In this brief review, the focus is on both effects of the NSAIDs and COX-2 inhibitors on blood pressure and CV events. The literature was searched using PubMed for both clinical trials and observational studies reviewing the relations among NSAIDs, blood pressure, and CV events. Clinical trial results for NSAIDs and COX-2 inhibitors have shown varying levels of destabilization of blood pressure control in treated hypertensive patients as well as variable incident rates of the development of arrhythmias, congestive heart failure, myocardial infarction, and stroke. The non-selective and COX-2 selective NSAIDs can be used with care in selected arthritis patients with hypertension and stable CV disorders (excluding congestive heart failure and moderate to severe kidney dysfunction) when the individual clinical benefit of anti-inflammatory therapy outweighs the CV and gastrointestinal risk.

Impact of non-steroidal anti-inflammatory drugs (NSAIDs) on cardiovascular outcomes in patients with stable atherothrombosis or multiple risk factors

BackgroundWe aimed to assess whether the use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with an increased risk of cardiovascular (CV) events in stable patients with established atherothrombosis or multiple risk factors. MethodsWe analysed the 23,728 European patients of the REACH Registry; 20,588 (86.8%) had established atherothrombotic disease and 3140 (13.2%) had multiple risk factors only. Aspirin (ASA) and/or NSAIDs use was determined at enrolment and ischemic events were recorded over two years of follow-up. cMACCE was defined as the composite of CV death, MI or stroke. Bleeding was defined as any bleeding leading to both hospitalisation and transfusion. ResultsThe mean age of population was 67.2±9.8years. At baseline, 1573 patients (6.6%) received NSAIDs and 15,395 (64.9%) received ASA. Four groups were defined: 1) no ASA/no NSAIDs, 2) ASA only, 3) NSAIDs only, 4) NSAIDs+ASA, with 7722 (32.5%), 14,433 (60.8%), 611 (2.6%) and 962 (4.1%) patients in these groups, respectively. Among the 22,028 (92.8%) with complete 2-year follow-up, 683 (3.2%) died from CV causes, while 395 (1.9%) had MI, 665 (3.1%) stroke, 1651 (7.6%) cMACCE and 199 (1.0%) bleeding. After adjustment, NSAID use was independently associated with an increased risk of stroke (OR 1.635; 95% CI 1.239–2.159, p<0.001), and a trend towards an increased bleeding rate (OR 1.554; CI 95% 0.960–2.51, p=0.07). No association was found between NSAID use and MI or MACCE. ConclusionsIn stable atherothrombosis patients, the use of NSAIDs appears to be independently associated with an increased cerebrovascular event risk.