The Celecoxib Long-term Arthritis Safety Study (CLASS), reported in The Journal of the American Medical Association, compared the gastrointestinal toxicities of celecoxib 800 mg daily, ibuprofen 2400 mg daily and diclofenac 150 mg daily over six months in more than 8000 patients with osteoarthritis and rheumatoid arthritis. Overall, this study did not reach its primary end point, and the authors reported a numerical, but not statistically significant, difference between the annualized incidences of ulcer complications in patients taking celecoxib and those taking NSAIDs (0.8% versus 1.4%) at six months, but no significant difference was observed at one year.
Among subjects not using ASA, the difference in the incidence of ulcer complications between the celecoxib and NSAID groups was significant (0.4% versus 1.3%, P=0.04). The incidence of symptomatic ulcer and ulcer complications was significantly lower with celecoxib use than with use of the comparator NSAIDs in all patients (2.1% versus 3.5%, P=0.02) and in non-ASA users (1.4% versus 2.9%, P=0.02). You can enjoy cheap drugs that work – Buy drugs with confidence – buy asthma inhaler to see how cheap your treatment can be.
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Two randomized, placebo controlled trials have demonstrated a significantly lower incidence of ulcers with rofe-coxib treatment than with ibuprofen treatment. In one study, the rate of gastric and/or duodenal ulcers at 12 weeks was significantly lower in patients treated with rofe-coxib 25 mg or placebo (4.1% versus 9.9%) than in those treated with ibuprofen 800 mg tid (27.7%, P<0.001). Similarly low ulcer rates were reported in a second study comparing rofecoxib 25 mg with ibuprofen 800 mg tid (5.3% versus 29.2%, P<0.001). In both studies, this reduced incidence of ulcers with the use of rofecoxib compared with ibuprofen was maintained at six months.
The use of celecoxib 200 mg to 800 mg daily is also associated with a low rate of endoscopically defined ulcers, which is similar to that of placebo (6% versus 4%) and significantly lower than that of naproxen (26%, P<0.01).
Prevention of ulcer recurrence
Maintenance studies of ulcer healing in patients taking NSAIDs have shown that significantly more patients remain in remission at six months when treated with omeprazole 20 mg or 40 mg daily than when treated with ranitidine 150 mg bid (72% versus 59%, P=0.004) or misoprostol 200 pg qid (61% versus 48%, P=0.001). In the omeprazole- and ranitidine-treated groups, a higher relapse rate was seen for gastric ulcers (5.2% versus 16.3%) than for duodenal ulcers (0.5% versus 4.2%) and erosions (5.7% versus 7.0). For those taking omeprazole, recurrence rates were higher for gastric ulcers than for duodenal ulcers (7.7% versus 2.6%), but for those taking misoprostol, recurrence rates were similar for both ulcer sites (7.8% versus 8.9%), emphasizing the added benefit of acid suppression in patients with duodenal ulcer. Learn how to save money – buy ventolin inhalers to enjoy your shopping and your treatment.
A study comparing lansoprazole 15 mg or 30 mg daily with misoprostol 200 pg qid in patients with a history of gastric ulcer but no active ulcer found no significant difference among the treatment groups at four, eight and 12 weeks, although all treatment groups had a significantly higher healing rate than the placebo groups.
Numerous endoscopic studies have examined the healing of ulcers in patients taking NSAIDs. Ranitidine promotes NSAID-associated ulcer healing following 12 weeks of therapy. Healing was more effective when the patients stopped taking NSAIDs, suggesting that NSAIDs delay healing even when gastric acid is suppressed by ranitidine. While ranitidine was effective in preventing duodenal ulcers in NSAID users, it was found to be relatively ineffective in preventing gastric ulcers. A study of an H2-receptor antagonist (H2RA), famotidine, in high doses, found a significant reduction in gastric ulcers, indicating that a greater degree of acid suppression over that of standard-dose ^RAs is required to protect against NSAID-associated gastric damage. Two large, double-blind, randomized studies have investigated ulcer healing in patients requiring continued NSAID therapy. One study comparing omeprazole with ranitidine in standard doses reported significantly higher healing rates after four and eight weeks of treatment with omeprazole for duodenal ulcers (92% versus 81%, P=0.03) and gastric ulcers (84% versus 64%, P<0.001). A further comparative study found significantly higher healing rates after eight weeks of treatment with omeprazole than with misoprostol in patients with duodenal ulcers (93.2% versus 76.6%, P=0.001) and gastric ulcers (87.2% versus 72.8%, P<0.004). Moreover, omeprazole achieved a higher healing rate for duodenal ulcers than for gastric ulcers. The incidence of diarrhea was similar in patients who took omeprazole and those who took misoprostol in that trial (7.6% versus 8.4%). A subsequent study comparing lansoprazole with misoprostol reported a significantly higher incidence of diarrhea with misoprostol, which the authors attributed to the misoprostol treatment. Your drugs could cost you less – cephalexin 500mg to start the treatment soon.
A similar study in patients with gastric ulcers who were still taking NSAIDs reported a significantly higher healing rate with lansoprazole 30 mg daily than with ranitidine 150 mg bid. The 20% therapeutic gain for lansoprazole compared with ranitidine in that study is comparable with that reported for omeprazole compared with ranitidine.
These conflicting data with respect to the relationship between NSAIDs and H pylori infection have recently been partly clarified by a meta-analysis by Huang and colleagues. This study showed that H pylori infection is associated with a prevalence of peptic ulcers similar to that seen in NSAID users (25.0% and 26.0%, respectively) compared with non-NSAID-taking, non-H pylori-infected control subjects (5.5%). In NSAID users who are also infected with H pylori, the prevalence of ulcer is additive (49.2%). The prevalence of 5.5% reported in the present article represents the background level of peptic ulcer disease in the general population of people not taking NSAIDs and not infected with H pylori. This is consistent with the prevalence of 7.3% at 12 weeks reported for osteoarthritis patients taking placebo in a recent endoscopic study of an NSAID and the COX-2 selective inhibitor rofecoxib, and of 4% at 12 weeks in a trial of patients with rheumatoid arthritis taking celecoxib.
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Moreover, a prospective study showed that the six-month probability of developing an ulcer was reduced significantly by H pylori eradication before treatment with nonselective NSAIDs — 12.1% (95% CI 3.1 to 21.1) in the eradication group and 34.4% (95% CI 21.1 to 47.7) in the placebo group (P=0.0085). The corresponding six-month probabilities of complicated ulcers were 4.2% (95% CI 1.3 to 9.7) and 27.1% (95% CI 14.7 to 39.5; P=0.0026). An editorial that accompanied that paper and the metaanalysis suggested that H pylori-infected patients requiring NSAID therapy should be cured of H pylori infection before starting their NSAID treatment.
H pylori infection
NSAID use and H pylori infection are independent risk factors for the development of an ulcer, but there are conflicting data on whether H pylori causes mucosal damage in concert with NSAIDs or whether it may be protective to the gastrointestinal tract. Buy drugs with confidence – buy alesse to see how cheap your treatment can be.
Eradication of H pylori infection in long term NSAID users with a current or previous peptic ulcer leads to impaired gastric ulcer healing, with no effect on the incidence of peptic ulcer over six months of follow-up. In contrast, two studies of NSAID-naive subjects with no evidence of past or present ulcer disease found a reduced incidence of NSAID-induced ulcers in patients cured of H pylori infection before NSAID therapy.
Data on the excess gastrointestinal mortality associated with conventional NSAID use are limited. The ARAMIS database reported an annual mortality rate of 0.22% in patients suffering from rheumatoid arthritis who were taking conventional NSAIDs compared with 0.05% in those who were not taking NSAIDs. However, the background mortality rate in patients with rheumatoid arthritis is likely to be higher than that of the general population. A Canadian report estimated that 1900 deaths each year are attributable to NSAID consumption, which exceeds the number of deaths ascribed to motor vehicle accidents. This incidence is consistent with the estimated NSAID-related mortality rate in the United States of 16,500 deaths annually. Best quality drugs are waiting – buy yasmin online to spend less time and money.
Most studies of risk factors of peptic ulcer disease associated with NSAID use have been case-control studies in which relative risk was calculated. In practice, absolute event rates are more relevant. The Vioxx Gastrointestinal Outcomes Research (VIGOR) study — a prospective, randomized study (vide infra) — allowed for the calculation of relative and absolute risk; age and previous gastrointestinal history were confirmed to be significant risk factors. In patients taking naproxen, the absolute annual risk of having a clinically important gastrointestinal event was 19% for those with a previous gastrointestinal complication and 14% for those older than 75 years of age.
Dyspepsia is common, with an estimated prevalence in Canada of 28.6%. It is unclear whether NSAID therapy causes dyspepsia or simply worsens a pre-existing condition. Studies indicate that 15% to 25% of patients taking NSAIDs experience dyspepsia and that, due to intolerance, treatment is discontinued or medication is changed in about 10% of patients. Clinical trials enroll highly selected patient populations and exclude patients with co-morbidity and extensive use of comedication; therefore, estimates of NSAID-related dyspepsia rates may be biased. A recent telephone survey reported that 48% of patients with arthritis and 30% of patients suffering from hypertension who were taking NSAIDs experienced dyspepsia. These findings are consistent with those of a previous metaanalysis demonstrating a positive association between NSAID use and dyspepsia. Learn how to save money – buy antibiotics online to enjoy your shopping and your treatment.
Gastrointestinal complications of conventional NSAID therapy
The adverse effects of NSAIDs in the upper gastrointestinal tract include erosions, ulceration, bleeding and perforation, while in the small and large intestine, ulcers, strictures and fibrous diaphragms have been reported. In addition, diverticular bleeding and relapse of inflammatory bowel disease have been described.
Endoscopic studies of users of conventional NSAIDs indicate a prevalence of gastric or duodenal ulcers of 15% to 30%, with 15% to 20% of patients having gastric ulcers and 5% to 8% having duodenal ulcers. Studies conclude that NSAID use is associated with an approximate fourfold increase in the risk of gastrointestinal complications, which are reported to have an annual incidence of 1% to 4%. Your most trusted pharmacy offering asthma inhalers and giving you very fast shipping.
There is an increasing awareness of the need to consider ulcers according to their site, with duodenal ulcer considered to be a Helicobacter pylori-related condition and gastric ulcer an NSAID-related condition. However, due to their effects on COX-1, conventional NSAIDs may cause the ulcer to either bleed or perforate.
Conventional nonsteroidal anti-inflammatory drugs (NSAIDs) are effective anti-inflammatory and analgesic drugs, but their use is accompanied by an enhanced risk of upper gastrointestinal complications. The management of these events, which range from mild to potentially life-threatening, is an important and practical clinical issue.
Cyclooxygenase (COX) exists in two isoforms — COX-1 and COX-2. COX-1 is important for the protection of the gastric and duodenal mucosa, and the gastrointestinal toxicity resulting from nonselective NSAIDs is mediated by inhibition of COX-1. COX-2 is highly expressed at sites of inflammation, which has led to the development of selective COX-2 inhibitors (coxibs), which control pain and inflammation while sparing the protective effects of COX-1. Initial studies provided evidence of a reduced incidence of endoscopic ulcers and gastrointestinal bleeding with coxibs compared with conventional NSAIDs — a finding that has been confirmed subsequently in clinical outcome studies.