Prior Nonsteroidal Anti-inflammatory Drugs Research Articles

Association between Non-Steroidal Anti-Inflammatory Drug Use and Major Cardiovascular Outcomes in Patients with Acute Coronary Syndrome in the Arabian Gulf.

Objectives: Studies on the association between non-steroidal anti-inflammatory drugs (NSAIDs) and major adverse cardiovascular events (MACE) in the Arabian Gulf are scarce. The aim of this study was to evaluate the association between NSAIDs use and MACE in acute coronary syndrome (ACS) patients in the Arabian Gulf region. Methods: Data were analyzed from 3007 consecutive patients diagnosed with ACS admitted to 29 hospitals in four Arabian Gulf countries from January 2012 to January 2013, as well as being on prior NSAIDs use during the index admission. The MACE included stroke/transient ischemic attacks (TIAs), myocardial infarction (MI), all-cause mortality and readmissions for cardiac reasons. Results: The overall mean age of the cohort was 62 ± 12 years, and 9.6% (n = 290) of the patients were on prior NSAID use during the index admission. At 12-months follow-up, after adjusting for confounding factors, patients on NSAIDs were significantly more likely to have had MACE (adjusted OR (aOR), 1.89; 95% confidence interval (CI): 1.44-2.48; p < 0.001). Specifically, the higher event rates observed were stroke/TIA (aOR, 2.50; 95% CI: 1.51-4.14; p < 0.001) and readmissions for cardiac reasons (aOR, 2.09; 95% CI: 1.59-2.74; p < 0.001), but not MI (aOR, 1.26; 95% CI: 0.80-1.99; p = 0.320) and all-cause mortality (aOR, 0.79; 95% CI: 0.46-1.34; p = 0.383). Conclusions: NSAIDs use was associated with significant stroke/TIA events as well as readmissions for cardiac reasons. However, NSAIDs were not associated with increased MIs or all-cause mortality rates in patients with ACS in the Arabian Gulf.

Effects of prior antiplatelet and/or nonsteroidal anti-inflammatory drug use on mortality in patients undergoing abdominal surgery for abdominal sepsis

BackgroundThe effects of prior antiplatelet and/or nonsteroidal anti-inflammatory drug (NSAID) use on mortality in critically ill patients remain unclear. We investigated the relationship between antiplatelet and/or NSAID use and mortality in patients who had undergone surgery for sepsis caused by intra-abdominal infection. MethodsWe obtained data from adult patients (aged >18 years) admitted to the intensive care unit after abdominal surgery due to intra-abdominal infection. The patients were categorized into those with and without prior antiplatelet and/or NSAID use. ResultsOverall, 241 patients were enrolled, with 76 in the antiplatelet and/or NSAID use group and 165 in the non-use group. The 60-day survival probabilities for the antiplatelet and/or NSAID use and non-use groups were 85.5% and 73.3%, respectively, and this difference was significant (P = .040). In the multivariate analysis of 28-day mortality, higher Acute Physiology and Chronic Health Evaluation II score (P < .001), Simplified Acute Physiology Score III (P < .001), and blood transfusion within 5 days postoperatively (P = .034) were significant mortality risk factors. In the multivariate analysis of 60-day mortality, higher Acute Physiology and Chronic Health Evaluation II score (P = .002), Simplified Acute Physiology Score III (P < .001), and blood transfusion within 5 days postoperatively (P = .006) were also significant mortality risk factors. However, prior drug use (P = .036) was a factor in reducing mortality. ConclusionPatients with a prior history of antiplatelet and/or NSAID use had a higher 60-day survival than those who did not use these drugs. Prior antiplatelet and/or NSAID use was significantly associated with a reduction in 60-day mortality.

Prevalence of NSAID use among people with COVID-19 and the association with COVID-19-related outcomes: Systematic review and meta-analysis.

AimRecent reports of potential harmful effects of nonsteroidal anti‐inflammatory drugs (NSAIDs) in treating patients with coronavirus disease 2019 (COVID‐19) have raised great concern.MethodsWe searched the PubMed, EMBASE, Cochrane Library and MedRxiv databases to examine the prevalence of NSAID use and associated COVID‐19 risk, outcomes and safety.ResultsTwenty‐five studies with a total of 101 215 COVID‐19 patients were included. Prevalence of NSAID use among COVID‐19 patients was 19% (95% confidence interval [CI] 14‐23%, no. of studies [n] = 22) and NSAID use prior to admission or diagnosis of COVID‐19 was not associated with an increased risk of COVID‐19 (adjusted odds ratio [aOR] = 0.93, 95% CI 0.82‐1.06, I 2 = 34%, n = 3), hospitalization (aOR = 1.06, 95% CI 0.76‐1.48, I 2 = 81%, n = 5), mechanical ventilation (aOR = 0.71, 95% CI 0.47‐1.06, I 2 = 38%, n = 4) or length of hospital stay. Moreover, prior use of NSAIDs was associated with a decreased risk of severe COVID‐19 (aOR = 0.79, 95% CI 0.71‐0.89, I 2 = 0%, n = 7) and death (aOR = 0.68, 95% CI 0.52‐0.89, I 2 = 85%, n = 10). Prior NSAID administration might also be associated with an increased risk of stroke (aOR = 2.32, 95% CI 1.04‐5.2, I 2 = 0%, n = 2), but not myocardial infarction (aOR = 1.49, 95% CI 0.25‐8.92, I 2 = 0, n = 2) and composite thrombotic events (aOR = 1.56, 95% CI 0.66‐3.69, I 2 = 52%, n = 2).ConclusionBased on current evidence, NSAID use prior to admission or diagnosis of COVID‐19 was not linked with increased odds or exacerbation of COVID‐19. NSAIDs might provide a survival benefit, although they might potentially increase the risk of stroke. Controlled trials are still required to further assess the clinical benefit and safety (e.g., stroke and acute renal failure) of NSAIDs in treating patients with COVID‐19.

41 Clinical Outcomes among COVID-19 Patients Taking Non-Steroidal Anti-Inflammatory Drugs

Concerns over the use of non-steroidal anti-inflammatory drugs (NSAIDs) for the management of fever and myalgia in COVID-19 patients were raised after four cases of critical illness in young, otherwise healthy patients who took NSAIDS were observed in France. France’s health minister subsequently made a recommendation to use acetaminophen in lieu of ibuprofen. However, the association between NSAID use and outcomes in COVID-19 illness has not been adequately studied. The objective of this study is to determine whether an association exists between prior NSAID use and COVID-19 illness severity.

Prior Routine Use of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and Important Outcomes in Hospitalised Patients with COVID-19.

Coronavirus disease 2019 (COVID-19) infection causes acute lung injury, resulting from aggressive inflammation initiated by viral replication. There has been much speculation about the potential role of non-steroidal inflammatory drugs (NSAIDs), which increase the expression of angiotensin-converting enzyme 2 (ACE2), a binding target for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to enter the host cell, which could lead to poorer outcomes in COVID-19 disease. The aim of this study was to examine the association between routine use of NSAIDs and outcomes in hospitalised patients with COVID-19. This was a multicentre, observational study, with data collected from adult patients with COVID-19 admitted to eight UK hospitals. Of 1222 patients eligible to be included, 54 (4.4%) were routinely prescribed NSAIDs prior to admission. Univariate results suggested a modest protective effect from the use of NSAIDs, but in the multivariable analysis, there was no association between prior NSAID use and time to mortality (adjusted HR (aHR) = 0.89, 95% CI 0.52–1.53, p = 0.67) or length of stay (aHR 0.89, 95% CI 0.59–1.35, p = 0.58). This study found no evidence that routine NSAID use was associated with higher COVID-19 mortality in hospitalised patients; therefore, patients should be advised to continue taking these medications until further evidence emerges. Our findings suggest that NSAID use might confer a modest benefit with regard to survival. However, as this finding was underpowered, further research is required.

Efficacy of duloxetine by prior NSAID use in the treatment of chronic osteoarthritis knee pain: A post hoc subgroup analysis of a randomized, placebo-controlled, phase 3 study in Japan

BackgroundA previously conducted placebo-controlled, randomized, phase 3 study of 353 Japanese patients with knee osteoarthritis (OA) showed significant improvements for duloxetine vs placebo in pain and health-related quality of life (HRQoL) (ClinicalTrials.gov Identifier: NCT02248480). Reported here are post hoc subgroup analyses evaluating the efficacy of duloxetine according to the pattern of prior nonsteroidal anti-inflammatory drug (NSAID) use. MethodsPatients with knee OA pain received once-daily duloxetine or placebo for 14 weeks. Pain was evaluated using the Brief Pain Inventory (BPI) and HRQoL was evaluated using the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC). Patients were divided into four subgroups based on their prior NSAID use: (i) no prior NSAID use; (ii) low-frequency NSAID use (<14 days/month); (iii) high-frequency transdermal NSAID use (transdermal NSAIDs only; ≥14 days/month for the 3 months before study entry); and (iv) high-frequency other NSAID use (eg, oral NSAIDs only, both oral and transdermal NSAIDs; ≥14 days/month for the 3 months before study entry). ResultsIn each of the four prior NSAID use subgroups, there were greater reductions in BPI average pain severity score for duloxetine vs placebo at all timepoints during the 14-week treatment period; the treatment*prior NSAID use interaction was not statistically significant. In each subgroup, the proportion of patients achieving a ≥50% reduction in BPI average pain severity score was higher for duloxetine vs placebo. In each subgroup, there were greater reductions in WOMAC total score for duloxetine vs placebo at all timepoints; the treatment*prior NSAID use interaction was not statistically significant. In each subgroup, there were greater reductions at Week 14 in WOMAC pain, stiffness, physical function, and total scores for duloxetine vs placebo. ConclusionsDuloxetine was consistently effective with respect to pain relief and HRQoL in Japanese patients with knee OA pain, regardless of the pattern of prior NSAID use.

NSAID Use and Incident Cognitive Impairment in a Population-based Cohort.

Nonsteroidal anti-inflammatory drugs (NSAIDs) may prevent dementia, but previous studies have yielded conflicting results. This study estimated the association of prior NSAID use with incident cognitive impairment in the population-based Epidemiology of Hearing Loss Study (EHLS, n=2422 without cognitive impairment in 1998-2000). Prospectively collected medication data from 1988-1990, 1993-1995, and 1998-2000 were used to categorize NSAID use history at the cognitive baseline (1998-2000). Aspirin use and nonaspirin NSAID use were separately examined. Cox regression models were used to estimate the associations between NSAID use history at baseline and incident cognitive impairment in 2003-2005 or 2009-2010. Logistic regression analyses were used to estimate associations with a second outcome, mild cognitive impairment/dementia, available in 2009-2010. Participants using aspirin at baseline but not 5 years prior were more likely to develop cognitive impairment (adjusted hazard ratio=1.77; 95% confidence interval=1.11, 2.82; model 2), with nonsignificant associations for longer term use. Nonaspirin NSAID use was not associated with incident cognitive impairment or mild cognitive impairment/dementia odds. These results provided no evidence to support a potential protective effect of NSAIDs against dementia.

Nonsteroidal anti-inflammatory drugs and the risk of nonmelanoma skin cancer.

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been assigned a promising role in the chemoprevention of various malignancies. However, epidemiological data on the association between NSAID use and nonmelanoma skin cancer (NMSC) are limited. To explore whether patients regularly exposed to systemic NSAIDs are at a reduced risk of basal cell carcinoma (BCC) or squamous cell carcinoma (SCC), we conducted a population-based case-control analysis using the Clinical Practice Research Datalink, a United Kingdom primary care database. We identified 65,398 patients with incident BCC and 7,864 patients with incident SCC diagnosed between 1995 and 2013 and matched 1 and 4 NMSC-free controls to each BCC and SCC case, respectively, on age, sex, general practice, calendar time and years of history in the database. We compared prior NSAID exposure between cases and controls using multivariate conditional logistic regression analyses controlling for several potential confounders. Overall, we found no association between NSAID use and BCC, but when looking exclusively at users of single NSAID substances there was a suggestion of a reduced BCC risk in regular users of aspirin and ibuprofen (adjusted odds ratio [adj. OR]: 0.92, 95% confidence interval [CI]: 0.85-0.99 and adj. OR: 0.61, 95% CI: 0.48-0.78, respectively). The risk of SCC was slightly decreased in regular users of any NSAIDs (adj. OR: 0.89, 95% CI: 0.82-0.97), with the strongest risk reduction observed in current users of coxibs (adj. OR: 0.77, 95% CI: 0.62-0.95). These findings provide evidence that patients predisposed to NMSC might benefit from chemoprevention with NSAIDs.

AB0865 Factors Which Influence the Effect of Analgesic Therapy

BackgroundEffective of pain relief is an important element of the treatment of rheumatic diseases. Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most popular class of analgesics. To predict their effect, depending...

Risk factors of Clostridium difficile-associated diarrhea in children

To explore the risk factors of Clostridium difficile-associated diarrhea (CDAD) in children. From December 2010 to March 2011, the hospitalized diarrheal patients under 18 years old at Beijing Children's Hospital were tested for Clostridium difficile. The CDAD(+) patients were selected and their fecal specimens were PCR-positive for tcdA and (or) tcdB genes. And the patients with healthcare facility-associated-CDAD (HCFA-CDAD) were selected from the group of CDAD(+). The CDAD patients were selected and their fecal specimens were PCR-negative for tcdA and (or) tcdB genes. And the 1:3 matched controls per case were selected from those hospitalized patients without diarrhea at the same department with similar diseases during the same period. The potential predictors of CDAD included age, gender, co-morbidities, prior hospitalization, the administration of C. difficile-active antibiotics during prior 24 hours, recent (< 1 month) exposure to antibiotics or acid-blocking medications or nonsteroidal anti-inflammatory drug (NSAID), C-reactive protein (CRP) and white blood cell (WBC), etc. Multivariate Logistic regression models were created to identify the independent predictors of CDAD. Among 93 PCR tests, 35 were positive in fecal samples. There were HCFA-CDAD (n = 30) and CDAD(-) (n = 58). Thirty-five CDAD(+) hospitalized patients were compared with 105 controls. According to multivariate analyses, the predictors of CDAD included prior hospitalization (P < 0.01, OR = 0.002), CRP(P = 0.008, OR = 3.465), NSAID (P = 0.015, OR = 13.950) and WBC (P = 0.003, OR = 8.063). The administration of NSAID, elevated CRP and abnormal WBC are significantly associated with CDAD.

Long-Term Follow-Up of 1,000 Patients Cured of Helicobacter pylori Infection Following an Episode of Peptic Ulcer Bleeding

To evaluate the effect of Helicobacter pylori (H. pylori) eradication on ulcer bleeding recurrence in a prospective, long-term study including 1,000 patients. Patients with peptic ulcer bleeding were prospectively included. Prior non-steroidal anti-inflammatory drug (NSAID) use was not considered exclusion criteria. H. pylori infection was confirmed by rapid urease test, histology, or (13)C-urea breath test. Several eradication therapies were used. Subsequently, ranitidine 150 mg o.d. was administered until eradication was confirmed by (13)C-urea breath test 8 weeks after completing therapy. Patients with therapy failure received a second, third, or fourth course of eradication therapy. Patients with eradication success did not receive maintenance anti-ulcer therapy and were controlled yearly with a repeat breath test. NSAID use was not permitted during follow-up. Thousand patients were followed up for at least 12 months, with a total of 3,253 patient-years of follow-up. Mean age 56 years, 75% males, 41% previous NSAID users. In all, 69% had duodenal ulcer, 27% gastric ulcer, and 4% pyloric ulcer. Recurrence of bleeding was demonstrated in three patients at 1 year (which occurred after NSAID use in two cases, and after H. pylori reinfection in another one), and in two more patients at 2 years (one after NSAID use and another after H. pylori reinfection). The cumulative incidence of rebleeding was 0.5% (95% confidence interval, 0.16-1.16%), and the incidence rate of rebleeding was 0.15% (0.05-0.36%) per patient-year of follow up. Peptic ulcer rebleeding virtually does not occur in patients with complicated ulcers after H. pylori eradication. Maintenance anti-ulcer (antisecretory) therapy is not necessary if eradication is achieved. However, NSAID intake or H. pylori reinfection may exceptionally cause rebleeding in H. pylori-eradicated patients.

Use of non-steroidal anti-inflammatory drugs and risk of Parkinson’s disease: nested case-control study

Objective To evaluate the relation between Parkinson’s disease and prior use of non-steroidal anti-inflammatory drugs (NSAIDs) in a large cohort of men.Design Case-control analysis nested in the Physicians’ Health Study....

Risk of dementia and AD with prior exposure to NSAIDs in an elderly community-based cohort

Nonsteroidal anti-inflammatory drugs (NSAIDs) may prevent Alzheimer dementia (AD). We analyzed the association of prior NSAID exposure with incident dementia and AD in the Adult Changes in Thought population-based cohort aged > or = 65 years (median 74.8) at enrollment. Participants were members of Group Health, which provided computerized pharmacy dispensing records from 1977 onward. We studied 2,736 dementia-free enrollees with extensive prior pharmacy data, following them biennially for up to 12 years to identify dementia and AD. Cox proportional hazards regression assessed association of dementia or AD with NSAID use graded in standard daily doses (SDD) dispensed over 2 years (e.g., heavy use = 500 + SDD), with some analyses also adding consecutive biennial self-reports of NSAID use. Pharmacy records identified 351 participants (12.8%) with history of heavy NSAID use at enrollment. Another 107 became heavy users during follow-up. Some 476 individuals developed incident dementia, 356 with AD (median onset ages 83.5 and 83.8 years). Contrary to the hypothesis that NSAIDs protect against AD, pharmacy-defined heavy NSAID users showed increased incidence of dementia and AD, with adjusted hazard ratios of 1.66 (95% confidence interval, 1.24-2.24) and 1.57 (95% confidence interval, 1.10-2.23). Addition of self-reported exposure data did not alter these results. These findings differ from those of other studies with younger cohorts. The results observed elsewhere may reflect delayed onset of Alzheimer dementia (AD) in nonsteroidal anti-inflammatory drug (NSAID) users. Conceivably, such delay could result in increased AD incidence in late old age. The relation of NSAID use and AD pathogenesis needs further investigation.

Fundic Gland Polyp Dysplasia Is Common in Familial Adenomatous Polyposis

Fundic gland polyps (FGPs) are common in familial adenomatous polyposis (FAP) but have been considered nonneoplastic. Gastric carcinoma arises from FGPs in FAP presumably from a dysplasia-carcinoma pathway. Our study examined the prevalence of FGPs and FGP dysplasia in FAP and identified endoscopic or demographic features associated with FGPs and dysplasia. Demographic and endoscopic information were obtained prospectively from 75 consecutive subjects undergoing upper-endoscopic surveillance for FAP. Systematic biopsy specimens of FGPs, normal-appearing fundic mucosa, and antral mucosa for Helicobacter pylori were obtained. Multivariable analysis assessed the association of demographic or endoscopic factors with the presence of FGP or FGP dysplasia. FGPs were detected in 88% of subjects and were dysplastic in 41% (38% low grade, 3% high grade). H pylori infection was rare in subjects with vs without FGPs (1.5% vs 33.3%, P = .005). In the multivariable analysis larger FGP size (odds ratio [OR], 4.0; 95% confidence interval [CI], 1.1-14.4), higher stage of duodenal polyposis (OR, 2.3; 95% CI, 1.2-4.5), and antral gastritis (OR, 11.2; 95% CI, 1.2-103.9) were associated with FGP dysplasia. Exposure to acid-suppressive medications was associated with a marked decrease in dysplastic FGPs (OR, 0.14; 95% CI, 0.03-0.64). The majority of FAP patients have FGPs and nearly half will have dysplastic FGPs. There is an inverse relationship between H pylori and FGPs. FGP dysplasia is associated with larger polyp size, increased severity of duodenal polyposis, and antral gastritis. Acid-suppressive therapy use appears protective against dysplasia in FGPs.

Interactions of stroke, nonsteroidal anti-inflammatory drugs, and APOE status in dementia risk

In this issue of Neurology ®, two independent reports1,2 once again confirm the saliency of the apolipoprotein epsilon 4 (APOE4) allele as a risk factor for Alzheimer disease (AD) or dementia. However, these studies go on to evaluate how APOE4 may be influenced by two other well-known AD/dementia risk factors, one of which, stroke, has been suggested to increase dementia risk,3 and one of which, nonsteroidal anti-inflammatory drug (NSAID) use, has been suggested to decrease AD risk.4 In a relatively large cohort, Szekely et al.1 show that the putative AD protective effects of prior NSAID exposure may owe almost exclusively to decreased risk in APOE4 carriers, with little to no reduction of the ORs for AD among NSAID-using, non-APOE4 subjects. This finding confirms earlier epidemiologic work by Hayden et al.,5 who also observed a significant AD protective effect of NSAIDs that was most notable in APOE4 subjects. Collectively, these studies could go far to explaining several paradoxes surrounding the now voluminous literature on inflammation and AD. The AD cortex (and its embedded vasculature) are clearly subject to chronic, innate inflammatory responses,6 yet AD treatment trials with NSAIDs have been equivocal at best.7 Perhaps beneficial effects in APOE4 subjects have been masked by an absence of benefit in non-APOE4 carriers—a possibility given that only one previous AD/NSAID treatment trial8 included APOE status as a covariate. …

Celecoxib Plus Aspirin Versus Naproxen and Lansoprazole Plus Aspirin: A Randomized, Double-Blind, Endoscopic Trial

Patients requiring low-dose aspirin along with nonsteroidal anti-inflammatory drugs are at increased risk for gastrointestinal injury. This study compared the incidence of gastroduodenal ulcers in patients treated with low-dose aspirin and a cyclooxygenase-2 selective nonsteroidal anti-inflammatory drug or a nonselective nonsteroidal anti-inflammatory drug plus the proton pump inhibitor lansoprazole. Subjects 18 years or older with osteoarthritis, without gastroduodenal ulcer or erosive esophagitis at baseline endoscopy, and a cardiovascular indication for prophylaxis low-dose (81 or 325 mg) aspirin were prescribed open-label aspirin and blindly randomized to celecoxib 200 mg/day or naproxen 500 mg twice daily plus lansoprazole 30 mg once daily. Endoscopy was performed at 12 weeks or early termination. One thousand forty-five subjects were randomized and received at least 1 dose of study medication, and 854 (n = 426 celecoxib, n = 428 naproxen plus lansoprazole) subjects with both baseline and final visit endoscopies were evaluable for the primary efficacy analysis. Among these subjects, the rate of endoscopically confirmed gastroduodenal ulcers was not different in the celecoxib (9.9%) and naproxen plus lansoprazole (8.9%; treatment difference [95% confidence interval], 1.0% [-2.9% to 4.9%]) groups. In patients with osteoarthritis taking low-dose aspirin, the use of celecoxib or naproxen plus lansoprazole resulted in similar rates of gastroduodenal ulceration.

Efficacy and safety of etoricoxib 30 mg and celecoxib 200 mg in the treatment of osteoarthritis in two identically designed, randomized, placebo-controlled, non-inferiority studies

To compare the efficacy of etoricoxib 30 mg with the generally maximum recommended dose of celecoxib, 200 mg, in the treatment of osteoarthritis (OA) in two identically designed studies. Two multi-centre, 26-week, double-blind, placebo-controlled, non-inferiority studies were conducted, enrolling patients who were prior non-steroidal anti-inflammatory drug (NSAID) or acetaminophen users. There were 599 patients in study 1 and 608 patients in study 2 randomized 4:4:1:1 to etoricoxib 30 mg qd, celecoxib 200 mg qd or one of two placebo groups for 12 weeks. After 12 weeks, placebo patients were evenly distributed to etoricoxib or celecoxib based on their initial enrollment randomization schedule. The primary hypothesis was that etoricoxib 30 mg would be at least as effective as celecoxib 200 mg for the time-weighted average change from baseline over 12 weeks for Western Ontario and McMaster (WOMAC) Pain Subscale, WOMAC Physical Function Subscale and Patient Global Assessment of Disease Status. Active treatments were also assessed over the full 26 weeks. Adverse experiences were collected for safety assessment. In both studies, etoricoxib was non-inferior to celecoxib for all three efficacy outcomes over 12 and 26 weeks; both were superior to placebo (P < 0.001) for all three outcomes in each study over 12 weeks. The safety and tolerability of etoricoxib 30 mg qd and celecoxib 200 mg qd were similar over 12 and 26 weeks. Etoricoxib 30 mg qd was at least as effective as celecoxib 200 mg qd and had similar safety in the treatment of knee and hip OA; both were superior to placebo. ClinicalTrials.gov Identifiers: NCT00092768; NCT00092791.

HOW RELIABLE IS THE CLINICAL HISTORY OF NONSTEROIDAL ANTI-INFLAMMATORY DRUG USE IN PATIENTS WHO PRESENT WITH UPPER GASTROINTESTINAL HEMORRHAGE?

There is paucity of literature regarding the reliability of clinical history for assessing the use of nonsteroidal anti-inflammatory drugs (NSAIDs) in patients presenting with upper gastrointestinal hemorrhage. Platelet function testing using the PFA-100 has been used to detect the effects of NSAIDs on platelets. We hypothesized that surreptitious use of NSAIDs occurs only in a small minority of such patients. Study Design Adult hospitalized patients undergoing endoscopy for evaluation of melena, hematemesis, or coffee-ground emesis were included in the study. Exclusion criteria included hematocrit less than 25% or platelet count less than 100,000/mm3 as these factors cause invalid measurements by the platelet function analyzer. Results Sixty-three patients met inclusion criteria. Sixteen patients were excluded due to anemia and thrombocytopenia as above. The average (SD) age of patients was 53.65 (15.55) years. Caucasians formed 40% of the study population, whereas the remaining were African Americans. Patients were predominantly males (64%). Twenty-one percent of the patients tested had positive PFA-100 measurements that suggested NSAID use. However, 60% of those with positive PFA-100 test had denied a history of prior NSAID use. Conclusions Clinical history is not a reliable indicator of prior NSAID use in patients presenting with upper gastrointestinal bleeding. Alternate testing to evaluate for surreptitious use of NSAIDs should be considered in patients with bleeding due to non-HP, non-NSAID ulcers.

Nonsteroidal anti-inflammatory drug use and Alzheimer's disease risk: the MIRAGE Study

BackgroundNonsteroidal anti-inflammatory drugs (NSAID) use may protect against Alzheimer's disease (AD) risk. We sought examine the association between NSAID use and risk of AD, and potential effect modification by APOE-ε4 carrier status and ethnicity.MethodsThe MIRAGE Study is a multi-center family study of genetic and environmental risk factors for AD. Subjects comprised 691 AD patients (probands) and 973 family members enrolled at 15 research centers between 1996 and 2002. The primary independent and dependent variables were prior NSAID use and AD case status, respectively. We stratified the dataset in order to evaluate whether the association between NSAID use and AD was similar in APOE-ε4 carriers and non-carriers. Ethnicity was similarly examined as an effect modifier.ResultsNSAID use was less frequent in cases compared to controls in the overall sample (adjusted OR = 0.64; 95% CI = 0.38–1.05). The benefit of NSAID use appeared more pronounced among APOE-ε4 carriers (adjusted OR = 0.49; 95% CI = 0.24–0.98) compared to non-carriers, although this association was not statistically significant. The pattern of association was similar in Caucasian and African Americans.ConclusionsNSAID use is inversely associated with AD and may be modified by APOE genotype. Prospective studies and clinical trials of sufficient power to detect effect modification by APOE-ε4 carrier status are needed.

The safety profile, tolerability, and effective dose range of rofecoxib in the treatment of rheumatoid arthritis

Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit both cyclooxygenase (COX)-1 and COX-2 isoenzymes and are effective in the treatment of inflammatory disorders. This 8-week, double-masked, placebo-controlled trial was undertaken to assess the safety profile, tolerability, and effective dose range of once-daily rofecoxib, a COX-2-specific inhibitor, in the treatment of rheumatoid arthritis (RA). After a 3- to 15-day washout of prior NSAID therapy, 658 patients were randomly allocated to receive placebo or rofecoxib 5 mg, 25 mg, or 50 mg once daily. Safety profile, tolerability, and efficacy were evaluated after 2, 4, and 8 weeks of therapy. Six hundred fifty-eight patients (168, 158, 171, and 161 in the placebo and 5-mg, 25-mg, and 50-mg rofecoxib groups, respectively) were enrolled at 79 clinical centers in the United States. Mean age was 55 years, mean duration of RA was 10 years, and 506 (77%) of the 658 patients were female. All groups had similar baseline demographic characteristics. Patients taking rofecoxib 25 and 50 mg showed significant clinical improvement compared with those taking placebo; 43.9% in the rofecoxib 25-mg group and 49.7% in the rofecoxib 50-mg group completed the treatment period and achieved an American College of Rheumatology 20 response ( P = 0.025 and 0.001 vs placebo, respectively). The 5-mg dose of rofecoxib did not differ significantly from placebo. Patients in the rofecoxib 25- and 50-mg groups showed significant improvement in key individual efficacy measurements, including patient global assessment of pain, patient and investigator global assessment of disease activity, and Stanford Health Assessment Questionnaire Disability Index ( P < 0.05 vs placebo). Compared with placebo, significantly fewer patients in the 25-mg and 50-mg rofecoxib groups discontinued therapy because of lack of efficacy ( P = 0.02 and P = 0.032, respectively). Our results show that rofecoxib 25 and 50 mg once daily was effective and generally welltolerated in patients with RA.