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Christopher J Hawkey

Publications and source records attributed to Christopher J Hawkey.

16 recordsLinked to original sources
PubMed2006

Diagnosis of autoimmune gastritis by high resolution magnification endoscopy.

Endoscopic visualisation of gastric atrophy is usually not feasible with conventional endoscopy. Magnifying endoscopy is helpful to analyze the subepithelial microvascular architecture as well as the mucosal surface microstructure without tissue biopsy. Using this technique we were able to describe the normal gastric microvasculature pattern and we also identified characteristic patterns in two cases of autoimmune atrophic gastritis.

Autoimmune Diseases↗
PubMed2006

Gastrointestinal tolerability of lumiracoxib in patients with osteoarthritis and rheumatoid arthritis.

BACKGROUND & AIMS: The aim of this study was to evaluate the gastrointestinal safety of lumiracoxib, a novel selective cyclooxygenase-2 inhibitor. METHODS: Results from 15 Phase II and III randomized studies of lumiracoxib in osteoarthritis and rheumatoid arthritis were pooled. Patients received lumiracoxib (200/400 mg/day), celecoxib (200/400 mg/day), rofecoxib (25 mg once daily), diclofenac (75 mg twice daily), ibuprofen (800 mg 3 times daily), naproxen (500 mg twice daily), or placebo. Outcome measures included the incidence of definite or probable ulcer complications (perforations, obstructions, or bleedings as confirmed by an adjudication committee) and symptomatic upper gastrointestinal ulcers, the incidence of prespecified gastrointestinal adverse events, and the discontinuation rate caused by adverse events. All suspected ulcer complications in these 15 studies were adjudicated prospectively. Data from 2 endoscopic studies were pooled separately to assess the cumulative incidence of gastroduodenal ulcers >or=3 mm in diameter. RESULTS: Symptomatic upper gastrointestinal ulcers and ulcer complications were reduced nearly 10-fold with lumiracoxib (1.7 events per 100 patient-years [95% confidence interval, 1.09-2.39]) compared with nonselective nonsteroidal anti-inflammatory drugs (13.7 events per 100 patient-years [95% confidence interval, 9.47-18.82]). Symptomatic ulcer frequency was markedly lower with lumiracoxib (0.4%) than with nonselective nonsteroidal anti-inflammatory drugs (2.5%). Discontinuation rates due to gastrointestinal adverse events were higher for nonselective nonsteroidal anti-inflammatory drugs (8.4%) than for lumiracoxib (3.3%). In the endoscopy analysis, the cumulative frequency of ulcers >or=3 mm in diameter was reduced by >70% for lumiracoxib versus ibuprofen. CONCLUSIONS: Lumiracoxib exhibited a gastrointestinal safety profile superior to nonselective nonsteroidal anti-inflammatory drugs.

Aged↗
PubMed2005

Isolated crypts form spheres prior to full intestinal differentiation when grown as xenografts: an in vivo model for the study of intestinal differentiation and crypt neogenesis, and for the abnormal crypt architecture of juvenile polyposis coli.

We describe a model system in which single crypts, isolated from newborn rats, were embedded in a type I collagen gel and subcutaneously grafted to the flanks of nude mice, whereupon they underwent full intestinal morphogenesis. Small fragments of small intestine and colon were incubated with the divalent cation chelator EDTA, resulting in the release of crypts and villi. Released crypts were then suspended sparsely in type I collagen gel. Segments of gel containing a single crypt were grafted subcutaneously into a nude mouse. Grafts were harvested at weekly intervals. By 2 days, the mouth of the crypts had joined to seal the crypt and, within 1 week, the structure ballooned to form a spherical cystic structure lined by flattened epithelial cells showing no evidence of cytodifferentiation. After 2 weeks, host stromal cells had invaded the collagen and settled around this spherical crypt. At points where stromal cells appeared in contact with the crypt, the epithelium exhibited a more columnar phenotype. By 4 weeks, the 'crypt sphere' was surrounded by stroma expressing alpha-smooth muscle actin and, at this time, multiple buds appeared that gave rise to new crypts. By 5 weeks, villi had formed and cell lineages associated with the small intestine and colon were present; the original single crypt had transformed into a functional intestinal unit. Therefore, we have shown that a single crypt has the potential to grow, give rise to other crypts and dependent structures such as villi. This model has considerable potential for use in gene transfer experiments in the study of intestinal differentiation, and for the analysis of crypt neogenesis via crypt fission. Moreover, the appearances showed a close resemblance to those seen in juvenile polyposis syndrome (JPS), where the budding and fission of single crypts isolated by stromal overgrowth offers an alternative explanation for the histogenesis of JPS.

Adenomatous Polyposis Coli↗
PubMed2005

Glutathione S-transferase M1 polymorphism and metabolism of sulforaphane from standard and high-glucosinolate broccoli.

BACKGROUND: Broccoli consumption is associated with a reduction in the risk of cancer, particularly in persons with a functional glutathione S-transferase M1 allele, as opposed rotrose whose GSTM1 gene has been deleted. Sulforaphane, the major isothiocyanate derived from 4-methylsulfinylbutyl glucosinolate, is thought to be the main agent conferring protection. OBJECTIVE: We compared sulforaphane metabolism in GSTM1-null and GSTM1-positive subjects after they consumed standard broccoli and high-glucosinolate broccoli (super broccoli). DESIGN: Sixteen subjects were recruited into a randomized, 3-phase crossover dietary trial of standard broccoli, super broccoli, and water. Liquid chromatography linked to tandem mass spectrometry was used to quantify sulforaphane and its thiol conjugates in plasma and urine. RESULTS: GSTM1-null subjects had slightly higher, but statistically significant, areas under the curve for sulforaphane metabolite concentrations in plasma, a greater rate of urinary excretion of sulforaphane metabolites during the first 6 h after broccoli consumption, and a higher percentage of sulforaphane excretion 24 h after ingestion than did GSTM1-positive subjects. Consumption of high-glucosinolate broccoli led to a 3-fold greater increase in the areas under the curve and maximum concentrations of sulforaphane metabolites in plasma, a greater rate of urinary excretion of sulforaphane metabolites during the first 6 h after consumption, and a lower percentage of sulforaphane excretion after its ingestion than did the consumption of standard broccoli. CONCLUSIONS: GSTM1 genotypes have a significant effect on the metabolism of sulforaphane derived from standard or high-glucosinolate broccoli. It is possible that the difference in metabolism may explain the greater protection that GSTM1-positive persons gain from consuming broccoli. The potential consequences of consuming glucosinolate-enriched broccoli for GSTM1-null and -positive persons are discussed.

Adolescent↗
PubMed2005

Cyclooxygenase-2 inhibitors.

PURPOSE OF REVIEW: The purpose of this review is to summarize new information regarding the use of selective inhibitors of the cyclooxygenase-2 enzyme, emphasizing recent developments regarding cardiovascular risk. RECENT FINDINGS: Selective cyclooxygenase-2 inhibitors are as effective as nonselective nonsteroidal antiinflammatory drugs in relieving pain and inflammation but are associated with significantly fewer gastric, duodenal, and intestinal ulcers and ulcer complications. Cyclooxygenase-2 inhibitors may also reduce colorectal polyp development or recurrence as well as reduce the risk of colorectal and esophageal cancer. Some, but not all, studies have suggested increased myocardial infarction with certain cyclooxygenase-2 inhibitors, in particular rofecoxib. It is unclear whether this is a class effect because there are inconclusive data to incriminate celecoxib despite a relatively large number of clinical trials enrolling a large number of patients. Rofecoxib was voluntarily withdrawn by the manufacturer. The European Medicines Agency concluded that cyclooxygenase-2 inhibitors are contraindicated in patients with established cardiovascular disease, should be used with caution in patients with risk factors, and were justified in patients at risk for serious gastrointestinal adverse events. SUMMARY: Rofecoxib, but perhaps not all cyclooxygenase-2 inhibitors, may be associated with increased risk for myocardial infarction. It is unclear whether nonselective nonsteroidal antiinflammatory drugs increase or decrease the rate of myocardial infarction. The final truth awaits further studies.

Animals↗
PubMed2004

Stem cell transplantation for Crohn's disease.

There is much interest in the possibility that haematopoietic stem cell transplantation might benefit patients with inflammatory bowel disease, with an emphasis on Crohn's disease. Case reports of patients with Crohn's disease undergoing stem cell transplantation for other reasons, or specifically for Crohn's disease, support the view that major improvements can be achieved, with even the possibility of a cure in a small number of, but certainly not all, cases. The development of Crohn's disease in a previously normal patient receiving an allogeneic transplant from an individual with the NOD2 mutation illustrates the importance of the genotype of the immune system. Population of the lamina propria by myofibroblasts with the donor's phenotype shows that non-immune mechanisms make also play a part. A clinical trial to determine the value of stem cell transplantation in Crohn's disease has been set up under the supervision of the European Group for Blood and Marrow Transplantation.

Crohn Disease↗
PubMed2004

Pharmacology and gastrointestinal safety of lumiracoxib, a novel cyclooxygenase-2 selective inhibitor: An integrated study.

BACKGROUND AND AIMS: Lumiracoxib is a structurally novel, acidic selective inhibitor of cyclooxygenase (COX)-2. We coordinated existing methodologies in a single study to evaluate potency, selectivity, and effect on the human gastrointestinal tract. METHODS: Twenty four healthy subjects (aged 18-45 years, 12 female) received high dose lumiracoxib (800 mg every day), standard dose naproxen (500 mg twice a day), or placebo for 8 days in a double-blind randomized crossover study. At the start and end of each dosing period, COX-2 selectivity was assessed by ex vivo serum thromboxane B(2) (COX-1) and lipopolysaccharide stimulated prostaglandin (PG) E(2) (COX-2), mucosal injury by endoscopy, and small and large bowel permeability by 0- to 5-hour and 5- to 24-hour (51)Cr-EDTA absorption. Plasma lumiracoxib was measured 2 hours after dosing on day 8 and vortex-stimulated ex vivo gastric mucosal PGE(2) synthesis at the end of each treatment period by enzyme immunoassay. RESULTS: Lumiracoxib was well absorbed and demonstrated similar potency to naproxen as a COX-2 inhibitor (77% and 66% inhibition, respectively, vs. placebo), but it differed in being more selective (24% and 97% inhibition of thromboxane B(2) vs. placebo). Gastric PGE(2) was reduced by 69% by naproxen (P < 0.001 vs. placebo) and 29% by lumiracoxib (P < 0.01 vs. placebo and naproxen). No subjects developed gastroduodenal erosions on lumiracoxib (vs. 75% on naproxen and 12.5% on placebo). (51)Cr-EDTA absorption increased significantly with naproxen but not lumiracoxib. CONCLUSIONS: Lumiracoxib is a potent selective inhibitor of COX-2 that causes little or no endoscopically detected stomach or duodenal injury or changes in bowel permeability.

Adolescent↗
PubMed2004

Lactobacillus plantarum 299: beneficial in vitro immunomodulation in cells extracted from inflamed human colon.

BACKGROUND AND AIM: The present study determined the pattern of cytokine secretion (interleukin [IL]-1beta, tumor necrosis factor [TNF]-alpha, interferon [IFN]-gamma and IL-10) and their cellular sources in mononuclear cells isolated from colonic mucosa from normal and ulcerative colitis (UC) in response to probiotic and pathogenic bacteria. METHODS: Mononuclear cells were extracted from normal and active UC colonic mucosa and incubated with pure sonicates of probiotic, commensal, and pathogenic bacteria. Cytokine secretion was measured in culture supernatant and intracellular cytokine staining measured using fluorescent-activated cytometry. RESULTS: In mononuclear cells isolated from normal mucosa, significant increases in mean IL-1beta were observed with enteropathogenic Escherichia coli (286.3 +/- 138.7 pg/mL P < 0.05) and E. coli (440.5 +/- 194.0 pg/mL P < 0.01) compared with unstimulated control cells (16.7 +/- 4.8 pg/mL). In contrast, mononuclear cells isolated from active UC mucosa produced significant increases in mean IL-1beta in response to stimulation with Salmonella dublin (230.5 +/- 38.8 pg/mL P < 0.05), enteropathogenic E. coli (231.7 +/- 45.3 pg/mL P < 0.05) and E. coli (465.4 +/- 60.2 pg/mL P < 0.001) compared with unstimulated control cells (60.7 +/- 17.1 pg/mL). Escherichia coli also produced significant mean increases of TNF-alpha and IFN-gamma compared with unstimulated control cells. No significant increases in IL-1beta, TNF-alpha or IFN-gamma were observed with Lactobacillus plantarum in cells derived from normal or inflamed mucosa. Strikingly, incubation of L. plantarum with mononuclear cells isolated from active UC mucosa resulted in significant increases of mean IL-10 (327 +/- 53.5 pg/mL, P < 0.05) compared with unstimulated control cells (29.7 +/- 13.2 pg/mL). Intracellular cytokine staining confirmed T-cell and macrophage IL-10 production after L. plantarum stimulation. CONCLUSIONS: Lactobacillus plantarum demonstrates beneficial immunomodulatory activity by increasing IL-10 synthesis and secretion in macrophages and T-cells derived from the inflamed colon. This may provide a mechanism through which probiotic bacteria ameliorate inappropriate inflammation and induce tolerance.

Cells, Cultured↗
PubMed2003

Assessment of non-steroidal anti-inflammatory drug (NSAID) damage in the human gastrointestinal tract.

Aspirin is widely prescribed and confers considerable benefit to patients by reducing cardiovascular and cerebrovascular morbidity and mortality. Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective analgesics, antipyretics and reduce the inflammatory component in conditions such as rheumatoid arthritis. However, both agents are associated with an increased risk of gastrointestinal symptoms and the potentially serious consequences of gastroduodenal ulceration, bleeding and perforation. The introduction of highly selective cyclo-oxygenase (COX)-2 inhibitors or the coprescription gastroprotective agents with nonselective NSAIDs have offered strategies to reduce the incidence of such events. This review article analyzes the quantitative techniques that can be employed by clinical pharmacologists and the clinical studies performed to assess NSAID damage in the gastrointestinal tract.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2003

Serious lower gastrointestinal clinical events with nonselective NSAID or coxib use.

BACKGROUND & AIMS: Epidemiologic studies suggest nonsteroidal anti-inflammatory drugs (NSAIDs) increase the risk for lower gastrointestinal (GI) clinical events, but data from prospective trials are lacking. Cyclooxygenase (COX)-2-selective inhibitors decrease upper GI clinical events but the effect on lower GI events has not been determined. We performed a post hoc analysis of serious lower GI clinical events with a nonselective NSAID and a COX-2-selective agent in a prospective, double-blind, randomized GI outcomes trial. METHODS: A total of 8076 rheumatoid arthritis patients 50 years or older (or 40 years or older on corticosteroid therapy) expected to require NSAIDs for 1 year or greater were randomly assigned to naproxen 500 mg twice daily or rofecoxib 50 mg daily. The rate of serious lower GI clinical events, defined as bleeding with a 2 g/dL drop in hemoglobin or hospitalization, or hospitalization for perforation, obstruction, ulceration, or diverticulitis, was determined. RESULTS: The rate of serious lower GI events per 100 patient-years was 0.41 for rofecoxib and 0.89 for naproxen (relative risk, 0.46; 95% confidence interval [CI], 0.22-0.93; P = 0.032). Serious lower GI events accounted for 39.4% of all serious GI events (complicated upper GI event or lower GI event) among patients taking naproxen and 42.7% among those taking rofecoxib. CONCLUSIONS: Serious lower GI events occurred at a rate of 0.9% per year in rheumatoid arthritis patients taking the nonselective NSAID naproxen, accounting for nearly 40% of the serious GI events that developed in these patients. Serious lower GI events were 54% lower with the use of the selective COX-2 inhibitor rofecoxib.

Adult↗
PubMed2003

Characterization of etoricoxib, a novel, selective COX-2 inhibitor.

Etoricoxib is a potent selective COX-2 inhibitor in man. Ex vivo whole-blood assays assessed COX-2 inhibition after oral administration of etoricoxib in single (5-500 mg) and multiple (25-150 mg) once-daily doses to healthy human subjects. A separate study examined ex vivo gastric mucosal PGE2 synthesis after etoricoxib (120 mg qd), naproxen (500 mg bid), or placebo for 5 days. The effect of etoricoxib 120 mg qd on the COX-1-mediated antiplatelet effects of low-dose aspirin (ASA) was also assessed. The mean (time)-weighted average inhibition (WAI) of lipopolysaccharide (LPS)-stimulated PGE2 (COX-2 assay) vcrsus placebo was dose related after single (range: 3.1%-99.1%) and multiple doses (range: 52.5%-96.7%). PGE2 remained significantly inhibited 24 hours postdose at steady state. Inhibition of LPS-stimulated PGE2 showed a strong relationship with etoricoxib plasma concentrations; ex vivo, IC50 was almost identical to in vitro. Multiple dosing of etoricoxib (up to 150 mg qd) showed no important effects on serum TXB2, bleeding time, or platelet aggregation (COX-1-mediated effects). The nonselective nonsteroidal anti-inflammatory (NSAID) naproxen significantly inhibited (approximately 78%) ex vivo prostaglandin synthesis in gastric mucosa; etoricoxib had no effect. Etoricoxib did not interfere with the antiplatelet effects of low-dose ASA, as assessed by serum TXB2 and platelet aggregation. Etoricoxib was generally well tolerated, even at doses above the clinical dose range. Based on these results, etoricoxib is a potent selective inhibitor of COX-2 after single and multiple dosing regimens and does not inhibit prostaglandin synthesis in the gastric mucosa, even at doses above the clinical dose range of 60 to 120 mg.

Adult↗
PubMed2002

Stratifying the risk of NSAID-related upper gastrointestinal clinical events: results of a double-blind outcomes study in patients with rheumatoid arthritis.

BACKGROUND & AIMS: Epidemiologic data indicate that the risk of nonsteroidal anti-inflammatory drug (NSAID)-related gastrointestinal (GI) clinical events varies based on patients' clinical characteristics. The authors determined risk factors for NSAID-related clinical upper GI events and the event rates, absolute risk reductions, and numbers needed to treat for individual risk factors for a nonselective NSAID and a selective cyclooxygenase 2 inhibitor in a double-blind outcomes trial. METHODS: Eight thousand seventy-six rheumatoid arthritis patients aged >or=50 years (or >or=40 on corticosteroid therapy) were randomly assigned to rofecoxib 50 mg daily or naproxen 500 mg twice daily for a median of 9 months. The development of clinical upper GI events (bleeding, perforation, obstruction, and symptomatic ulcer identified on clinically indicated work-up) was assessed. RESULTS: Significant risk factors included prior upper GI events, age >or=65, and severe rheumatoid arthritis (RR, 2.3-3.9). Patients administered naproxen who had prior upper GI complications or who were aged >or=75 years had 18.84 or 14.46 events per 100 patient-years, and the risk of events remained constant over time. The reduction in events with rofecoxib was similar in high- and low-risk subgroups (RR, 0.31-0.68). The number needed to treat with rofecoxib instead of naproxen to avert 1 GI event was 10-12 in highest risk patients (prior event, age >or=75 years, or severe rheumatoid arthritis), 17-33 in patients with other risk factors, and 42-106 in low-risk patients. CONCLUSIONS: NSAID-related GI events increase dramatically with risk factors such as prior events or older age. Ten to twelve high-risk patients need to be treated with a protective strategy such as the selective cyclooxygenase 2 inhibitor, rofecoxib, to avert a clinical GI event.

Adrenal Cortex Hormones↗
PubMed2002

Toxicity of mycophenolate mofetil in patients with inflammatory bowel disease.

Trials of mycophenolate mofetil (MMF) in inflammatory bowel disease (IBD) suggest that it may be useful in patients intolerant of azathioprine. We examined the safety and efficacy of MMF in IBD patients intolerant of or unresponsive to azathioprine. Twelve patients [seven with Crohn's disease (CD); seven women; mean age 40 years, range 14-76 years] were treated with MMF 500 mg b.i.d. for a mean of 12.5 weeks. Intolerance was defined as the development of side effects that resolved on discontinuing MMF. Improvement was described as symptomatic improvement, decreased steroid use, or disease entering endoscopic remission. Four patients responded with symptomatic improvement and reduced steroids or mesalazine requirement. Three patients developed headache, nausea, or arthralgia. Three patients developed profuse bloody diarrhea, and in two cases with previously quiescent ulcerative colitis (UC), the source was shown to be ulcers in a drug-induced colitis with histologic features similar to those previously reported in four renal transplant patients on MMF. There is no clear evidence of efficacy of MMF in the treatment of IBD, and its use in this condition should be confined to a randomized controlled trial. Moreover, as patients with UC may be unduly prone to colonic injury, MMF may not be a suitable drug for its treatment.

Administration, Oral↗
PubMedDate not supplied

Comparison of lumiracoxib with naproxen and ibuprofen in the Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET), reduction in ulcer complications: randomised controlled trial.

BACKGROUND: Cyclo-oxygenase 2 (COX2)-selective inhibitors should reduce ulcer complications compared with non-selective non-steroidal anti-inflammatory drugs, but evidence is limited, and the possibility that these inhibitors increase cardiovascular events has been raised. The Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET) aimed to assess gastrointestinal and cardiovascular safety of the COX2 inhibitor lumiracoxib compared with two non-steroidal anti-inflammatory drugs, naproxen and ibuprofen. METHODS: 18325 patients age 50 years or older with osteoarthritis were randomised to lumiracoxib 400 mg once daily (n=9156), naproxen 500 mg twice daily (4754), or ibuprofen 800 mg three times daily (4415) for 52 weeks, in two substudies of identical design (lumiracoxib vs ibuprofen or naproxen). Randomisation was stratified for low-dose aspirin use and age. The primary endpoint was the difference in time-to-event distribution of upper gastrointestinal ulcer complications (bleeding, perforation, or obstruction); analysis was by modified intention to treat. The principle measure of adverse cardiovascular events was the Antiplatelet Trialists' Collaboration endpoint (myocardial infarction, stroke, or cardiovascular death); this analysis was intention to treat. FINDINGS: 81 (0.44%) patients did not start treatment and 7120 (39%) did not complete the study. In patients not taking aspirin, the cumulative 1-year incidence of ulcer complications was 1.09% (95% CI 0.82-1.36) with non-steroidal anti-inflammatory drugs (64 events) versus 0.25% (95% CI 0.12-0.39) with lumiracoxib (14 events; hazard ratio 0.21 [95% CI 0.12-0.37], p<0.0001). Reductions in ulcer complications were also significant in the overall population (0.34 [0.22-0.52], p<0.0001) but not in those taking aspirin (0.79 [0.40-1.55], p=0.4876). In the overall population, 0.55% (50/9127) of those on non-steroidal anti-inflammatory drugs and 0.65% (59/9117) of those on lumiracoxib reached the cardiovascular endpoint (1.14 [0.78-1.66], p=0.5074). INTERPRETATION: Lumiracoxib showed a three to four-fold reduction in ulcer complications compared with non-steroidal anti-inflammatory drugs without an increase in the rate of serious cardiovascular events, suggesting that lumiracoxib is an appropriate treatment for patients with osteoarthritis.

Aged↗
PubMedDate not supplied

Comparison of lumiracoxib with naproxen and ibuprofen in the Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET), cardiovascular outcomes: randomised controlled trial.

BACKGROUND: The potential for cyclo-oxygenase 2 (COX2)-selective inhibitors to increase the risk for myocardial infarction is controversial. The Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET) aimed to assess gastrointestinal and cardiovascular safety of the COX2 inhibitor lumiracoxib compared with two non-steroidal anti-inflammatory drugs, naproxen and ibuprofen. METHODS: 18325 patients age 50 years or older with osteoarthritis were randomised to lumiracoxib 400 mg once daily (n=9156), naproxen 500 mg twice daily (4754), or ibuprofen 800 mg three times daily (4415) in two substudies of identical design. Randomisation was stratified for low-dose aspirin use and age. The primary cardiovascular endpoint was the Antiplatelet Trialists' Collaboration endpoint of non-fatal and silent myocardial infarction, stroke, or cardiovascular death. Analysis was by intention to treat. FINDINGS: 81 (0.44%) patients did not start treatment and 7120 (39%) did not complete the study. At 1-year follow-up, incidence of the primary endpoint was low, both with lumiracoxib (59 events [0.65%]) and the non-steroidal anti-inflammatory drugs (50 events [0.55%]; hazard ratio 1.14 [95% CI 0.78-1.66], p=0.5074). Incidence of myocardial infarction (clinical and silent) in the overall population in the individual substudies was 0.38% with lumiracoxib (18 events) versus 0.21% with naproxen (ten) and 0.11% with lumiracoxib (five) versus 0.16% with ibuprofen (seven). In the naproxen substudy, rates of myocardial infarction (clinical and silent) did not differ significantly compared with lumiracoxib in the population not taking low-dose aspirin (hazard ratio 2.37 [95% CI 0.74-7.55], p=0.1454), overall (1.77 [0.82-3.84], p=0.1471), and in patients taking aspirin (1.36 [0.47-3.93], p=0.5658). In the ibuprofen substudy, these rates did not differ between lumiracoxib and ibuprofen in the population not taking low-dose aspirin (0.75 [0.20-2.79], p=0.6669), overall (0.66 [0.21-2.09], p=0.4833), and in patients taking aspirin (0.47 [0.04-5.14], p=0.5328). INTERPRETATION: The primary endpoint, including incidence of myocardial infarction, did not differ between lumiracoxib and either ibuprofen or naproxen, irrespective of aspirin use. This finding suggests that lumiracoxib is an appropriate treatment for patients with osteoarthritis, who are often at high cardiovascular risk and taking low-dose aspirin.

Aged↗