Llorente Melero M J, Tenías Burillo J M, Zaragoza Marcet A
Unit of Rheumatology, Lluís Alcanyís Hospital, Xátiva, Valencia, Spain.
Rev Esp Enferm Dig. 2002 Jan;94(1):7-18.
The existence of two isoforms of cyclo-oxygenase (COX), COX-1 and COX-2, is now well established. Because inhibition of COX-1 by nonsteroidal anti-inflammatory drugs (NSAIDs) is linked to gastrointestinal (GI) damage, agents with a better COX-2/COX-1 inhibition ratio may have less GI toxicity. The aim of this study was to compare the incidence of upper gastrointestinal bleeding (UGIB) in association with specific NSAIDs including the new "COX-2 preferential" inhibitors. PATIENTS Y METHOD: Individual incidence of NSAID-related UGIB in a health-authority area was estimated, based on cases of UGIB, sales of non-aspirin NSAIDs, and data of used doses in community subjects, during a four-year period. Comparisons were made by calculating individual rate-ratio (RR) and 95% confidence interval (CI) taking as a reference the specific NSAID with the lowest incidence of UGIB.
The incidence of UGIB associated with thirteen specific NSAIDs included in the study varied greatly, from 1.7 per 1,000 person-years for aceclofenac to 25.8 per 1,000 person-years for ketorolac. The use of "COX-1 preferential" inhibitors versus "COX-2 preferential" inhibitors was associated with a RR of 5.3 (95% CI, 2.78-10.04), and between NSAIDs with "COX-1-COX-2 mixed" inhibition RR was 2.2 (95% CI, 1.13-4.28).
Our results show that there are differences in GI toxicity according to specific NSAIDs. A substantial reduction in number of cases of UGIB could result from the use of NSAIDs with a "COX-2 preferential" inhibition.
环氧化酶（COX）存在两种同工型，即COX-1和COX-2，这一点现已得到充分证实。由于非甾体抗炎药（NSAIDs）对COX-1的抑制作用与胃肠道（GI）损伤有关，因此具有更佳COX-2/COX-1抑制比的药物可能具有较低的胃肠道毒性。本研究的目的是比较包括新型“COX-2选择性”抑制剂在内的特定NSAIDs相关上消化道出血（UGIB）的发生率。
基于UGIB病例、非阿司匹林NSAIDs的销售量以及社区受试者的用药剂量数据，对某卫生管理区域内NSAIDs相关UGIB的个体发生率进行了为期四年的估算。以UGIB发生率最低的特定NSAIDs作为参照，通过计算个体率比（RR）和95%置信区间（CI）进行比较。
本研究纳入的13种特定NSAIDs相关UGIB的发生率差异很大，从醋氯芬酸的每1000人年1.7例到酮咯酸的每1000人年25.8例不等。使用“COX-1选择性”抑制剂与“COX-2选择性”抑制剂相比，RR为5.3（95%CI，2.78 - 10.04），而在具有“COX-1 - COX-2混合”抑制作用的NSAIDs之间，RR为2.2（95%CI，1.13 - 4.28）。
我们的结果表明，不同的特定NSAIDs在胃肠道毒性方面存在差异。使用具有“COX-2选择性”抑制作用的NSAIDs可使UGIB病例数大幅减少。
