COX2 inhibitor could offer benefits over other anti-inflammatory drugs for osteoarthritis (pp 639, 665, 675)August 18, 2004Results of an international multi-centre study in this week's issue of THE LANCET suggest that the COX2 inhibitor lumiracoxib could be an effective treatment for osteoarthritis-its use was associated with an 80% reduction in gastric complications compared with other conventional anti-inflammatory drugs. The use of non-selective non-steroidal anti-inflammatory drugs (NSAIDs) is widespread to reduce the pain associated with osteoarthritis; however the side-effects of these drugs can be severe, sometimes leading to gastro-intestinal ulcer complications which account for around 7000 US and 1000 UK deaths each year. The development of Cyclo-oxygenase 2 (COX2)-selective inhibitors should reduce these ulcer complications, but evidence is limited, and the possibility that COX2 inhibitors increase cardiovascular events has been raised. TARGET (The Therapeutic Arthritis Research and Gastrointestinal Event Trial) assessed gastrointestinal and cardiovascular safety of the COX2 inhibitor lumiracoxib compared with the NSAIDs naproxen and ibuprofen. 18325 osteoarthritis patients (aged 50 years or older) were randomised to receive either lumiracoxib (9156 patients), naproxen (4754 patients), or ibuprofen (4415 patients) for1 year. The risk of ulcer complications was reduced among patients given lumiracoxib (0"25%) compared with patients using non-selective NSAIDs (1"09%); however this benefit did not apply for patients who were also taking aspirin. TARGET also demonstrated that the incidence of non-fatal and silent myocardial infarction, stroke, or cardiovascular death, which was low in the population, did not differ significantly between treatment groups (lumiracoxib 0"65% vs NSAIDs 0"55%), or when analysed by aspirin use, age, sex, high cardiovascular risk, or cerebrovascular history. "The fact that we enrolled osteoarthritis patients in the study who already had high blood pressure or other risk factors for coronary heart disease was important," says Dr. Michael E Farkouh, lead author on the cardiovascular outcomes paper (New York University School of Medicine, USA). Investigator Michael Doherty (University of Nottingham, UK) comments: "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". The TARGET study is critically evaluated in an accompanying commentary by Eric J Topol and Gary W Falk (Cleveland Clinic Foundation, USA - see p 639). With regard to cardiovascular outcomes they comment: 'The overall low frequency of myocardial events is important to put in context. Patients in TARGET were 50 years or older and nearly all those with myocardial infarction, stroke, coronary artery bypass surgery, or congestive heart failure were excluded. Less than 2% of the patients had a previous myocardial infarction or a revascularisation procedure. Unfortunately, this trial, like all others in the clinical development of coxibs, purposefully excluded patients with known and significant pre-existing coronary artery disease'. Topol and Falk also highlight concerns about lumiracoxib's liver toxicity and potential increase in heart attack if lumiracoxib is compared with naproxen alone: 'TARGET quantifies lumiracoxib's narrow benefit over two NSAIDs with a trade-off. For patients not taking aspirin, there is an absolute reduction of 0"72% in ulcer complications, with an excess of 2"0% of liver function test abnormalities. The putative benefit is further compromised if naproxen is the NSAID, with a 0"17% excess of myocardial infarction. For patients taking low-dose aspirin, it is hard to justify the coxib: there is no benefit in ulcer complication reduction, but the risk of myocardial infarction and hepatotoxicity persist.' | |||||||||||||||||||||
|
Related AIDS Current Events and AIDS News Articles New appropriate use criteria guide treatment of patients with heart blockage If you're committed to fitness, the decision to climb a couple of flights of stairs rather than take the elevator is clear. But if you develop chest pain on the way up, deciding how to treat the symptoms of clogged arteries in your heart is much more complicated. Einstein researchers find convincing evidence that probiotics are effective Up to one in five people on antibiotics stop taking their full course of antibiotic therapy due to diarrhea. Physicians could help patients avoid this problem by prescribing probiotics, according to a study by researchers at Albert Einstein College of Medicine of Yeshiva University published in American Family Physician. Charting HIV's rapidly changing journey in the body HIV is so deadly largely because it evolves so rapidly. With a single virus as the origin of an infection, most patients will quickly come to harbor thousands of different versions of HIV, all a little bit different and all competing with one another to most efficiently infect that person's cells. Genetic markers identified for alcohol response in UCSF Gallo study Researchers at the UCSF Ernest Gallo Clinic and Research Center have identified a region on the human genome that appears to determine how strongly drinkers feel the effects of alcohol and thus how prone they are to alcohol abuse. UC Davis researchers exploring gene therapy to fight AIDS The apparent success of a case in which German doctors cured a man of AIDS using a bone marrow transplant comes as no surprise to Gerhard Bauer, a UC Davis stem cell researcher. Study sheds light on causes of HIV dementia A new study led by researchers at Albert Einstein College of Medicine of Yeshiva University has clarified how two major variants of HIV differ in their ability to cause neurologic complications. New HIV film tackles stigma faced by teachers in Africa Addressing the discrimination against HIV-positive teachers in Africa is a key aim of a new documentary and accompanying book being launched in Senegal today by the Partnership for Child Development based at Imperial College London. Selenium may slow march of AIDS Increasing the production of naturally occurring proteins that contain selenium in human blood cells slows down multiplication of the AIDS virus, according to biochemists. Claudin 11 stops the leaks in neuronal myelin sheaths Devaux and Gow demonstrate how a tight junction protein called claudin 11 makes the neuronal myelin sheath a snug fit. ACP recommends routine HIV screening for all patients On World AIDS Day, the American College of Physicians (ACP) is giving doctors a call-to-action to routinely encourage HIV screening to all of their patients older than 13 years. This new practice guideline appears on the Annals of Internal Medicine Web site at www.annals.org. More AIDS Current Events and AIDS News Articles |
|||||||||||||||||||||
|
|||||||||||||||||||||
|
|||||||||||||||||||||