Effect of non-steroidal anti-inflammatory drugs on risk of Alzheimer's disease: systematic review and meta-analysis of observational studies.
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SUBMITTER: Etminan M
PROVIDER: S-EPMC165707 | biostudies-other | 2003 Jul
REPOSITORIES: biostudies-other
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Project description:BackgroundRandomised trials have highlighted the cardiovascular risks of non-steroidal anti-inflammatory drugs (NSAIDs) in high doses and sometimes atypical settings. Here, we provide estimates of the comparative risks with individual NSAIDs at typical doses in community settings.Methods and findingsWe performed a systematic review of community-based controlled observational studies. We conducted comprehensive literature searches, extracted adjusted relative risk (RR) estimates, and pooled the estimates for major cardiovascular events associated with use of individual NSAIDs, in different doses, and in populations with low and high background risks of cardiovascular events. We also compared individual drugs in pair-wise (within study) analyses, generating ratios of RRs (RRRs). Thirty case-control studies included 184,946 cardiovascular events, and 21 cohort studies described outcomes in >2.7 million exposed individuals. Of the extensively studied drugs (ten or more studies), the highest overall risks were seen with rofecoxib, 1.45 (95% CI 1.33, 1.59), and diclofenac, 1.40 (1.27, 1.55), and the lowest with ibuprofen, 1.18 (1.11, 1.25), and naproxen, 1.09 (1.02, 1.16). In a sub-set of studies, risk was elevated with low doses of rofecoxib, 1.37 (1.20, 1.57), celecoxib, 1.26 (1.09, 1.47), and diclofenac, 1.22 (1.12, 1.33), and rose in each case with higher doses. Ibuprofen risk was seen only with higher doses. Naproxen was risk-neutral at all doses. Of the less studied drugs etoricoxib, 2.05 (1.45, 2.88), etodolac, 1.55 (1.28, 1.87), and indomethacin, 1.30 (1.19, 1.41), had the highest risks. In pair-wise comparisons, etoricoxib had a higher RR than ibuprofen, RRR?=?1.68 (99% CI 1.14, 2.49), and naproxen, RRR?=?1.75 (1.16, 2.64); etodolac was not significantly different from naproxen and ibuprofen. Naproxen had a significantly lower risk than ibuprofen, RRR?=?0.92 (0.87, 0.99). RR estimates were constant with different background risks for cardiovascular disease and rose early in the course of treatment.ConclusionsThis review suggests that among widely used NSAIDs, naproxen and low-dose ibuprofen are least likely to increase cardiovascular risk. Diclofenac in doses available without prescription elevates risk. The data for etoricoxib were sparse, but in pair-wise comparisons this drug had a significantly higher RR than naproxen or ibuprofen. Indomethacin is an older, rather toxic drug, and the evidence on cardiovascular risk casts doubt on its continued clinical use. Please see later in the article for the Editors' Summary.
| S-EPMC3181230 | biostudies-literature
Project description:BackgroundThe association between the development of heart failure (HF) and use of nonsteroidal anti-inflammatory drugs (NSAIDs) is not well established.HypothesisUse of NSAIDs may increase the risk of incident HF.MethodsWe conducted a systematic review and meta-analysis of observational studies that reported odds ratio, relative risk, hazard ratio, or standardized incidence ratio comparing risk of incident HF in NSAID users vs nonusers. Pooled risk ratios (RR) and 95% confidence intervals (CI) for all NSAIDs and both subclasses (conventional NSAIDs and highly selective cyclooxygenase-2 inhibitors [COXIBs]) were calculated using a random-effect, generic inverse variance method.ResultsSeven studies with 7,543,805 participants were identified and included in our data analysis. Use of NSAIDs was associated with a significantly higher risk of developing HF, with a pooled RR of 1.17 (95% CI: 1.01-1.36). Subgroup analysis showed a significantly elevated risk among users of conventional NSAIDs (RR: 1.35, 95% CI: 1.15-1.57) but not users of COXIBs (RR: 1.03, 95% CI: 0.92-1.16).ConclusionsA significantly elevated risk of incident HF was observed among users of NSAIDs.
| S-EPMC6490752 | biostudies-literature
Project description:ObjectiveTo analyse the available evidence on cardiovascular safety of non-steroidal anti-inflammatory drugs.DesignNetwork meta-analysis.Data sourcesBibliographic databases, conference proceedings, study registers, the Food and Drug Administration website, reference lists of relevant articles, and reports citing relevant articles through the Science Citation Index (last update July 2009). Manufacturers of celecoxib and lumiracoxib provided additional data.Study selectionAll large scale randomised controlled trials comparing any non-steroidal anti-inflammatory drug with other non-steroidal anti-inflammatory drugs or placebo. Two investigators independently assessed eligibility.Data extractionThe primary outcome was myocardial infarction. Secondary outcomes included stroke, death from cardiovascular disease, and death from any cause. Two investigators independently extracted data.Data synthesis31 trials in 116 429 patients with more than 115 000 patient years of follow-up were included. Patients were allocated to naproxen, ibuprofen, diclofenac, celecoxib, etoricoxib, rofecoxib, lumiracoxib, or placebo. Compared with placebo, rofecoxib was associated with the highest risk of myocardial infarction (rate ratio 2.12, 95% credibility interval 1.26 to 3.56), followed by lumiracoxib (2.00, 0.71 to 6.21). Ibuprofen was associated with the highest risk of stroke (3.36, 1.00 to 11.6), followed by diclofenac (2.86, 1.09 to 8.36). Etoricoxib (4.07, 1.23 to 15.7) and diclofenac (3.98, 1.48 to 12.7) were associated with the highest risk of cardiovascular death.ConclusionsAlthough uncertainty remains, little evidence exists to suggest that any of the investigated drugs are safe in cardiovascular terms. Naproxen seemed least harmful. Cardiovascular risk needs to be taken into account when prescribing any non-steroidal anti-inflammatory drug.
| S-EPMC3019238 | biostudies-literature
Project description:ObjectiveTo conduct a systematic review of observational studies on the risk of acute myocardial infarction (AMI) with use of individual nonsteroidal anti-inflammatory drugs (NSAIDs).MethodsA search of Medline (PubMed) for observational studies published from 1990 to 2011 identified 3829 articles; 31 reported relative risk (RR) of AMI with use of individual NSAIDs versus nonuse of NSAIDs. Information abstracted in a standardized form from 25 publications was used for the meta-analysis on 18 independent study populations.ResultsRandom-effects RR (95% confidence interval (CI)) was lowest for naproxen 1.06 (0.94–1.20), followed by celecoxib 1.12 (1.00–1.24), ibuprofen 1.14 (0.98–1.31), meloxicam 1.25 (1.04–1.49), rofecoxib 1.34 (1.22–1.48), diclofenac 1.38 (1.26–1.52), indometacin 1.40 (1.21–1.62), etodolac 1.55 (1.16–2.06), and etoricoxib 1.97 (1.35–2.89). Heterogeneity between studies was present. For new users, RRs (95% CIs) were for naproxen, 0.85 (0.73–1.00); ibuprofen, 1.20 (0.97–1.48); celecoxib, 1.23 (1.00–1.52); diclofenac, 1.41 (1.08–1.86); and rofecoxib, 1.43 (1.21–1.66).Except for naproxen, higher risk was generally associated with higher doses, as defined in each study, overall and in patients with prior coronary heart disease. Low and high doses of diclofenac and rofecoxib were associated with high risk of AMI, with dose–response relationship for rofecoxib. In patients with prior coronary heart disease, except for naproxen, duration of use ?3 months was associated with an increased risk of AMI.ConclusionsMost frequently NSAIDs used in clinical practice, except naproxen, are associated with an increased risk of AMI at high doses or in persons with diagnosed coronary heart disease. For diclofenac and rofecoxib, the risk was increased at low and high doses.
| S-EPMC3749466 | biostudies-literature
Project description:The association between non-steroidal anti-inflammatory drugs (NSAIDs) and gastric cancer (GC) risk is controversial. The aim of this study is to evaluate the chemopreventive effect of NSAIDs for GC.A literature search was performed for relevant studies using the PubMed and Embase database (up to March 2016). Risk ratios (RRs) and 95% confidence intervals (CIs) were used as the effect measures. The dose-response analysis and subgroup analysis were also performed.Twenty-four studies were included. Our results indicated that NSAIDs could reduce GC risk (any NSAIDs: RR=0.78, 96%CI=0.72-0.85; aspirin: RR=0.70, 95%CI=0.62-0.80; non-aspirin NSAIDs: RR=0.86, 95%CI=0.80-0.94), especially for non-cardia GC risk. Moreover, the dose-response analysis indicated the risk of GC decreased by 11% and 5% for 2 years increment of any NSAIDs and aspirin use, respectively. There were nonlinear relationships between the frequency of any NSAIDs use and aspirin use and GC risk (P for non-linearity<0.01), with a threshold effect of 5 times/week. A monotonically decreasing trend was observed only for the frequency of less than 5 times/week.Our results indicate that NSAIDs is inversely associated with GC risk, especially for non-cardia GC risk. NSAIDs use may become a feasible approach to prevent GC.
| S-EPMC5354871 | biostudies-other
Project description:Background: Epidemiological evidences regarding the association between the use of non-steroidal anti-inflammatory drugs (NSAIDs) and the risk of prostate cancer (PC) is still controversial. Therefore, we conducted a meta-analysis to explore the controversy that exists. Methods: Electronic databases including Medline, EMBASE, Web of Science, Cochrane Library, BIOSIS, Scopus, CBM, CNKI, WANFANG, and CQVIP were used to search for and identify eligible studies published until December 31, 2017. Pooled effect estimates for the relative risk (RR) were computed through fixed-effects or random-effects models as appropriate. Publication bias was evaluated by Egger's and Begg's tests and potential sources of heterogeneity were investigated in subgroup analyses. Results: A total of 43 observational studies were eligible for this meta-analysis. A protective effect was identified for the intake of any NSAIDs on the risk of PC (pooled RR = 0.89, 95% CI = 0.81-0.98). Moreover, the long-term intake of NSAIDs (?5 years rather than ?4 years) was associated with reduced PC incidence (pooled RR = 0.882, 95% CI = 0.785-0.991). Aspirin intake was also associated with a 7.0% risk reduction of PC (pooled RR = 0.93, 95% CI = 0.89-0.96). The inverse association became stronger for advanced PC and PC with a Gleason score ?7 compared to the association with total PC. Interestingly, it was the daily dose (?1 pill/day) rather than, long-term aspirin intake (?4 or ?5 years) that was associated with reduced PC incidence (pooled RR = 0.875, 95% CI = 0.792-0.967). The pooled effects for non-aspirin NSAIDs demonstrated no significantly adverse or beneficial effects on total PC, advanced PC, or PC with Gleason score ?7, though all pooled RRs were >1. Conclusions: Our findings suggested a protective effect of the intake of any NSAIDs on the risk of PC, especially in those who took the NSAIDs for a long period. Moreover, aspirin intake was also associated with a decreased risk of PC, and there was a dose related association between aspirin intake and the risk of PC, while no significant effects of long-term aspirin intake were found on the PC incidence.
| S-EPMC6206266 | biostudies-literature
Project description:AimNon-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to control postoperative pain; however, their postoperative use has been associated with anastomotic leakage after gastrointestinal surgery. This systematic review and meta-analysis aimed to determine the correlation between the use of NSAIDs and anastomotic leakage.MethodsWe conducted a comprehensive electronic literature search up to August 2018 to identify studies comparing anastomotic leakage in patients with and without postoperative NSAID use following gastrointestinal surgery. We then carried out a meta-analysis using random-effects models to calculate odds ratios (OR) with 95% confidence intervals (CI).ResultsTwenty-four studies were included in this meta-analysis, including a total of 31 877 patients. Meta-analysis showed a significant association between NSAID use and anastomotic leakage (OR 1.73; 95% CI = 1.31-2.29, P < .0001). Subgroup analyses showed that non-selective NSAIDs, but not selective cyclooxygenase-2 inhibitors, were significantly associated with anastomotic leakage. However there was no significant subgroup difference between selective and non-selective NSAIDs.ConclusionResults of this meta-analysis indicate that postoperative NSAID use is associated with anastomotic leakage following gastrointestinal surgeries. Caution is warranted when using NSAIDs for postoperative analgesic control in patients with gastrointestinal anastomoses.
| S-EPMC6992684 | biostudies-literature
Project description:BackgroundNon-steroidal anti-inflammatory drugs (NSAID) have excellent anti-inflammatory and analgesic properties and are extensively used to treat post-traumatic or surgical musculoskeletal pain. Although an extensive literature exists on the administration of NSAID on animal bone healing, no systematic review and meta-analysis of animal studies that investigate the effect of NSAID administration on bone fracture healing. Objective of this study is to conduct a systematic review and meta-analysis to estimate the effect of NSAIDs administration on bone healing biomechanical and histomorphometric measurements in different animal models after bone fracture surgery.MethodsWe performed a systematic review and meta-analysis of animal studies to estimate the effect of NSAID administration after bone fracture on healing outcomes. We searched eight databases without limiting the search to starting date up to 1 February 2021 for articles on fractured bone healing in animal models in which NSAID were administered.ResultsOut of 6732 articles screened, 47 were included and 3 common bone healing outcomes were analysed: biomechanical properties (maximum force to break, stiffness, and work-to-failure), micro-computed tomography (μ-CT), and histomorphometric measurements. The studies were generally of low-quality scores because crucial information, especially concerning randomization, blinding, and allocation concealment, was poorly reported. Our results show that the negative effects of NSAID after bone fracture on certain biomechanical properties of the healing bones was not statistically significant in mice compared with other animals, in females compared with males, and in younger compared with older animals.ConclusionThe findings demonstrated that NSAIDs administration decreased the biomechanical properties of healing bones after fracture surgery in comparison to the control group. Moreover, different effect on certain outcomes was detected among different sites, sex of the animals, and the time of assessment.Trial registrationProtocol published and registered in SYstematic Review Center for Laboratory animal Experimentation (SYRCLE) in 2017, https://www.radboudumc.nl/getmedia/757ec408-7a9e-4635-8233-ae951effea54/Non-Steroidal-Anti-inflammatory-Drugs-and-bone-healing-in-animal-Models-Systematic-Review-and-Meta-Analysis.aspx.
| S-EPMC8268344 | biostudies-literature
Project description:ObjectiveWe aimed to assess the safety of topical non-steroidal anti-inflammatory drugs (NSAIDs) in the management of osteoarthritis (OA) in a systematic review and meta-analysis of randomized, placebo-controlled trials.MethodsA comprehensive literature search was undertaken in the MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and Scopus electronic databases. Randomized, double-blind, placebo-controlled, parallel-group trials that assessed adverse events (AEs) with topical NSAIDs in patients with OA were eligible for inclusion. Authors and/or study sponsors were contacted to obtain the full report of AEs. The primary outcomes were overall severe and serious AEs, as well as the following MedDRA System Organ Class (SOC)-related AEs: gastrointestinal, vascular, cardiac, nervous system, skin and subcutaneous tissue, musculoskeletal and connective tissue.ResultsThe search strategy identified 1209 records, from which 25 papers were included in the qualitative synthesis and 19 were included in the meta-analysis, after exclusions. Overall, more total AEs (odds ratio [OR] 1.16, 95% confidence interval [CI] 1.04-1.29; I2 = 0.0%) and more withdrawals due to AEs (OR 1.49, 95% CI 1.15-1.92; I2 = 0.0%) were observed with topical NSAIDs compared with placebo. The same results were achieved with topical diclofenac, largely driven by an increase in skin and subcutaneous tissue disorders (OR 1.73, 95% CI 0.96-3.10), although the difference was not statistically significant compared with placebo. No significant difference in the odds for gastrointestinal disorders was observed between topical NSAIDs and placebo (OR 0.96, 95% CI 0.73-1.27).ConclusionsTopical NSAIDs may be considered safe in the management of OA, especially with regard to low gastrointestinal toxicity. The use of topical NSAIDs in OA should be considered, taking into account their risk: benefit profile in comparison with other anti-OA treatments.
| S-EPMC6509095 | biostudies-literature
Project description:Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most widely used classes of medicines in the treatment of inflammation, fever, and pain. However, evidence has demonstrated that these drugs can induce significant toxicity. In the search for innovative strategies to overcome NSAID-related problems, the incorporation of drugs into cyclodextrins (CDs) has demonstrated promising results. This study aims to review the impact of cyclodextrin incorporation on the biopharmaceutical and pharmacological properties of non-steroidal anti-inflammatory drugs. A systematic search for papers published between 2010 and 2020 was carried out using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol and the following search terms: "Complexation"; AND "Cyclodextrin"; AND "non-steroidal anti-inflammatory drug". A total of 24 different NSAIDs, 12 types of CDs, and 60 distinct inclusion complexes were identified, with meloxicam and β-CD appearing in most studies. The results of the present review suggest that CDs are drug delivery systems capable of improving the pharmacological and biopharmaceutical properties of non-steroidal anti-inflammatory drugs.
| S-EPMC7996898 | biostudies-literature