Risk of adverse gastrointestinal outcomes in patients taking cyclo-oxygenase-2 inhibitors or conventional non-steroidal anti-inflammatory drugs: population based nested case-control analysis
Risk of adverse gastrointestinal outcomes in patients taking cyclo-oxygenase-2 inhibitors or conventional non-steroidal anti-inflammatory drugs: population based nested case-control analysis
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DOI：
10.1136/bmj.331.7528.1310
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发表时间：
2005-12-03
影响因子：
105.7
通讯作者：
Logan, R
中科院分区：
文献类型：
--
作者：
Hippisley-Cox, J;Coupland, C;Logan, R
目的比较服用不同环氧合酶-2抑制剂与非选择性非甾体抗炎药的患者发生上消化道不良事件的风险。设计巢式病例对照研究。设置367个有助于英国QRESEARCH数据库的一般实践，分布在英格兰，威尔士，参与者年龄在25岁或25岁以上的首次诊断为不良上消化道事件的患者2000年8月1日至2004年7月31日期间的胃溃疡或呕血患者，每个病例最多10名年龄、性别、日历时间匹配的对照，主要结果测量与暴露于塞来昔布、罗非昔布、布洛芬、双氯芬酸、萘普生、其它选择性和非选择性非甾体抗炎药、结果上消化道不良事件的发生率为1.36/1000人年（95%可信区间1.34 ~ 1.39）。我们确定了9407例事件病例和88867例匹配对照。不良胃肠道事件的风险增加与当前使用环氧合酶-2抑制剂和常规非甾体抗炎药相关。在调整混杂因素后，风险降低，但对于纳洛芬（调整后的比值比为2.12，95%置信区间为1.73 - 2.58）、双氯芬酸（1.96，1.78 - 2.15）和罗非昔布（1.56，1.30 - 1.87），风险仍然显著增加，但对于目前使用的塞来昔布（1.11，0.87 - 1.41），风险没有显著增加。我们发现与目前使用的溃疡愈合药物的临床重要的相互作用，消除了所有非甾体抗炎药组不良胃肠道事件的风险增加，但双氯芬酸除外，其比值比仍然增加（1.49，结论没有一致的证据表明任何新的环氧合酶抑制剂对胃肠道事件的安全性增强。2抑制剂与非选择性非甾体抗炎药相比。溃疡愈合药物的使用降低了所有非甾体抗炎药组不良胃肠道结局的风险增加，但双氯芬酸的风险增加仍然显著。
Objective To determine the risk of an adverse upper gastrointestinal event in patients taking different cyclo-oxygenase-2 inhibitors compared with non-selective non-steroidal anti-inflammatory drugs.Design Nested case-control study.Setting 367 general practices contributing to the UK QRESEARCH database, spread throughout every strategic health authority and each health board in England, Wales, and Scotland.Participants Patients aged 25 or more with a first ever diagnosis of an adverse upper gastrointestinal event (peptic ulcer or haematemesis) between I August 2000 and 31 July 2004 and up to 10 controls per case matched for age, sex, calendar time, and practice.Main outcome measures Unadjusted and adjusted odds ratios for adverse upper gastrointestinal events associated with exposure to celecoxib, rofecoxib, ibuprofen, diclofenac, naproxen, other selective and non-selective non-steroidal anti-inflammatory drugs, and aspirin.Results The incidence of adverse upper gastrointestinal events was 1.36 per 1000 person years (95% confidence interval 1.34 to 1.39). We identified 9407 incident cases and 88 867 matched controls. Increased risks of adverse gastrointestinal events were associated with current use of cyclo-oxygenase-2 inhibitors and with conventional non-steroidal anti-inflammatory drugs. Risks were reduced after adjustment for confounders but remained significantly increased for naproxen (adjusted odds ratio 2.12, 95% confidence interval 1.73 to 2.58), diclofenac (1.96, 1.78 to 2.15), and rofecoxib (1.56, 1.30 to 1.87) but not for current use of celecoxib (1.11, 0.87 to 1.41). We found clinically important interactions with current use Of ulcer healing drugs that removed the increased risks for adverse gastrointestinal events for all groups of non-steroidal anti-inflammatory drugs except diclofenac, which still had an increased odds ratio (1.49, 1.26 to 1.76).Conclusion No consistent evidence was found of enhanced safety against gastrointestinal events with any of the new cyclo-oxygenase-2 inhibitors compared with non-selective non-steroidal anti-inflammatory drugs. The use of ulcer healing drugs reduced the increased risk of adverse gastrointestinal outcomes with all groups of non-steroidal anti-inflammatory drugs, but for diclofenac the increased risk remained significant.