Gastrointestinal complications

Cure Arthritis Naturally

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Gastrointestinal (GI) side effects of NSAIDs range from mild dyspepsia to severe and even fatal perforated and bleeding ulcers. According to US national statistics, these drugs cause around 16,500 deaths each year and in the UK approximately 2500 people die annually from their GI side effects.42 Patients taking long-term NSAIDs have a point prevalence for gastric or duodenal ulcers of up to 20 percent.43 In the TARGET trial, estimates from the US suggest serious GI hemorrhage and perforation occur in 0.25 to 1.58 percent of users per year and result in at least 7000 deaths per annum in the USA and 1000 deaths every year in the UK.44 Precise figures are not available as patients often have associated risk factors such as smoking, alcohol, and concomitant drug use.2 The risk of fatal adverse reactions to NSAIDs may be higher; in the US NSAIDs carry a warning label stating a 2-4 percent risk of serious gastrointestinal reactions.19 Many patients who take these agents will terminate therapy due to abdominal pain, irrespective of proven GI complications. Further evidence of this is seen in the drop-out rate of many trials and in clinical practice.45 Up to 31 percent of the cost of managing arthritis patients is accounted for through the management of GI side effects. In a nested case-control study46 conducted between August 2000 and July 2004 involving 367 general practices in the UK to determine the risk of adverse upper GI events in patients taking different COX-2 inhibitors compared with nonselective NSAIDs, the incidence of adverse upper GI events was 1.36 per 1000 person years (95 percent CI 1.34 to 1.39). Increased risks of adverse GI events were associated with current use of COX-2 inhibitors and with conventional NSAIDs. No consistent evidence was found of enhanced safety for GI events with any of the new COX-2 inhibitors compared with nonselective NSAIDs. The use of ulcer healing drugs reduced the increased risk of adverse GI outcomes with all groups of NSAIDs, but for diclofenac the increased risk remained significant. A cohort study47 [III] examined 52,000 patients over 50 years old who had been prescribed one or more NSAID prescriptions over a two-year period against 74,000 controls. Follow-up was for three years looking at hospital admissions for gastrointestinal complaints. The risk was assessed as 0.2 percent per annum and remained the same with long-term use. A meta-analysis48[I] of GI complications of NSAIDs showed ibuprofen to have the lowest risk and used it as the comparator. The authors commented that ibuprofen is generally used in a low-dose regimen (up to 1600 mg a day) and demonstrated a dose-response curve. Higher daily doses of ibuprofen increase the relative risk towards that of the other NSAIDs. There is also a risk of lower GI events with NSAIDs, which may account for up to 40 percent of the GI side effects.49 They include bleeding, ulceration, stricture formation, and diverticuli-tis. A more recent systematic review highlights the elderly and those with a past history of GI side effects to be at higher risk; this reduces to baseline on withdrawal of the NSAID and confirms a dose-response effect with regard to gastric irritation.50[I] In a randomized controlled trial,51 GI toxicity with celecoxib versus NSAIDs for osteoarthritis and rheumatoid arthritis (the CLASS study), celecoxib was associated with a lower incidence of ulcer and ulcer-related complications combined, as well as other clinically important side effects compared with NSAIDs at standard dosages. The decrease in upper GI toxicity was strongest in those not taking aspirin con-comitantly. In the TARGET trial,44 two NSAIDs, naproxen and ibuprofen, were compared to a COX-2 inhibitor, lumiracoxib, to assess GI and cardiovascular safety. The latter showed a three- to four-fold decrease in ulcer related complications compared to NSAIDs, without an increase in the rate of serious cardiovascular events.

Prospective GI outcome studies show that COX-2 inhibitors significantly decrease the rate of endoscopic ulcers and clinical GI events as compared to nonselective NSAIDs. The NNT to avert one clinical event in one year is ^40 to 100. Their cost-effectiveness is higher in high risk patients (31 percent). An alternative to COX-2 agents is the concomitant use of gastroprotective agents with nonselective NSAIDs.52[I] Commonly used groups include: H2 antagonists (e.g. ranitidine), prostaglandin analogs (e.g. misoprostol) or proton pump inhibitors (e.g. omeprazole). A systematic review examined the effect of adding a proton pump inhibitor (PPI) or using a COX-2 antagonist versus NSAID alone. With a PPI the absolute risk reduction was 9 percent and the NNT 11; with COX-2 antagonist, the figures were 37 percent and 27 for the NNT.53[I]

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Osteoarthritis

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