Strand Vibeke
Division of Immunology and Rheumatology, Stanford University, Palo Alto, CA, USA.
Lancet. 2007 Dec 22;370(9605):2138-51. doi: 10.1016/S0140-6736(07)61909-6.
Cyclo-oxygenase-2 selective inhibitors and non-selective non-steroidal anti-inflammatory drugs (NSAIDs) are associated with increased risk of acute cardiovascular events. Only aspirin offers primary and secondary cardiovascular prophylaxis, but trials have not answered directly whether low-dose aspirin is cardioprotective with COX-2 inhibitors. A large inception cohort study showed that concomitant use of aspirin reduced risk of cardiovascular events when given with rofecoxib, celecoxib, sulindac, meloxicam, and indometacin but not when given with ibuprofen. In large trials assessing gastrointestinal safety, there were fewer gastrointestinal events in patients using both COX-2 inhibitors and aspirin than in those using non-selective NSAIDs and aspirin; significantly fewer uncomplicated upper gastrointestinal events took place in the MEDAL trial. Analysis of VIGOR and two capsule endoscopy studies showed significantly less distal gastrointestinal blood loss with COX-2 inhibitors than with non-selective NSAIDs. Endoscopy trials showed that low-dose aspirin does not diminish the gastrointestinal benefits of COX-2 inibitors over non-selective NSAIDs. In an elderly epidemiological cohort receiving aspirin, both celecoxib and rofecoxib reduced risk of admission for gastrointestinal events. Comparison of the cardiovascular and gastrointestinal risks is difficult: likelihood and severity of cardiovascular events differ between individuals, agents, and exposure. Mortality associated with gastrointestinal events is less frequent than with cardiovascular events, but asymptomatic ulcers can result in severe complications. Data support the conclusion that COX-2 inhibitors are preferable to non-selective NSAIDs in patients with chronic pain and cardiovascular risk needing low-dose aspirin, but relative risks and benefits should be assessed individually for each patient.
环氧化酶-2选择性抑制剂和非选择性非甾体抗炎药（NSAIDs）与急性心血管事件风险增加相关。只有阿司匹林具有一级和二级心血管预防作用，但试验尚未直接回答低剂量阿司匹林与COX-2抑制剂联用时是否具有心脏保护作用。一项大型队列起始研究表明，阿司匹林与罗非昔布、塞来昔布、舒林酸、美洛昔康和吲哚美辛联用时可降低心血管事件风险，但与布洛芬联用时则不然。在评估胃肠道安全性的大型试验中，同时使用COX-2抑制剂和阿司匹林的患者发生胃肠道事件的次数少于使用非选择性NSAIDs和阿司匹林的患者；在MEDAL试验中，无并发症的上消化道事件明显较少。对VIGOR试验和两项胶囊内镜研究的分析表明，与非选择性NSAIDs相比，COX-2抑制剂导致的远端胃肠道失血明显更少。内镜试验表明，低剂量阿司匹林不会削弱COX-2抑制剂相对于非选择性NSAIDs的胃肠道益处。在一个接受阿司匹林治疗的老年流行病学队列中，塞来昔布和罗非昔布均降低了胃肠道事件入院风险。比较心血管和胃肠道风险很困难：心血管事件的可能性和严重程度在个体、药物和暴露情况之间存在差异。与胃肠道事件相关的死亡率低于心血管事件，但无症状溃疡可能导致严重并发症。数据支持以下结论：对于需要低剂量阿司匹林的慢性疼痛和有心血管风险的患者，COX-2抑制剂优于非选择性NSAIDs，但应针对每位患者单独评估相对风险和益处。
