Hippisley-Cox Julia, Coupland Carol, Logan Richard
Division of Primary Care, University of Nottingham, Nottingham NG2 7RD.
BMJ. 2005 Dec 3;331(7528):1310-6. doi: 10.1136/bmj.331.7528.1310.
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.
Nested case-control study.
367 general practices contributing to the UK QRESEARCH database, spread throughout every strategic health authority and each health board in England, Wales, and Scotland.
Patients aged 25 or more with a first ever diagnosis of an adverse upper gastrointestinal event (peptic ulcer or haematemesis) between 1 August 2000 and 31 July 2004 and up to 10 controls per case matched for age, sex, calendar time, and practice.
Unadjusted and adjusted odds ratios for adverse upper gastrointestinal events associated with celecoxib, rofecoxib, ibuprofen, diclofenac, naproxen, other selective and non-selective non-steroidal anti-inflammatory drugs, and aspirin.
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).
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.
确定服用不同环氧化酶-2抑制剂的患者与非选择性非甾体抗炎药相比发生上消化道不良事件的风险。
巢式病例对照研究。
向英国QRESEARCH数据库提供数据的367家全科诊所，分布在英格兰、威尔士和苏格兰的每个战略卫生管理局及每个卫生委员会。
年龄在25岁及以上，在2000年8月1日至2004年7月31日期间首次被诊断为上消化道不良事件（消化性溃疡或呕血）的患者，每个病例最多匹配10名年龄、性别、日历时间和诊所相匹配的对照。
与塞来昔布、罗非昔布、布洛芬、双氯芬酸、萘普生、其他选择性和非选择性非甾体抗炎药以及阿司匹林相关的上消化道不良事件的未调整和调整后的比值比。
上消化道不良事件的发生率为每1000人年1.36例（95%置信区间1.34至1.39）。我们确定了9407例新发病例和88867名匹配对照。胃肠道不良事件风险增加与当前使用环氧化酶-2抑制剂及传统非甾体抗炎药有关。在对混杂因素进行调整后风险降低，但萘普生（调整后的比值比2.12，95%置信区间1.73至2.58）、双氯芬酸（1.96，1.78至2.15）和罗非昔布（1.56，1.30至1.87）的风险仍显著增加，而当前使用塞来昔布（1.11，0.87至1.41）的风险未增加。我们发现与当前使用溃疡愈合药物存在临床上重要的相互作用，这消除了除双氯芬酸外所有非甾体抗炎药组胃肠道不良事件增加的风险，双氯芬酸的比值比仍增加（1.49，1.26至1.76）。
与非选择性非甾体抗炎药相比，未发现任何一种新型环氧化酶-2抑制剂在预防胃肠道事件方面具有更高安全性的一致证据。使用溃疡愈合药物降低了所有非甾体抗炎药组胃肠道不良结局增加的风险，但双氯芬酸增加的风险仍然显著。
