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目的:评价选择性环氧化酶2(COX-2)抑制剂和传统的非甾体类抗炎药(NSMDs)在发生血管事件上的风险性。设计:对已发表和未发表随机试验的表格式资料进行荟萃分析,对传统 NSAIDs 的作用进行间接评估。资料来源:资料分别来源于 Medline 和 Embase(1966年1月至2005年4月);食品与药品管理局记录;以及诺华、辉瑞、默克公司的资料。回顾方法:符合以下条件的随机试验入组本研究:一种选择性 COX-2抑制剂与安慰剂比较或一种选择性 COX-2抑制剂与一种传统的 NSAID之间对比;用药持续时间至少4周;包含严重血管事件方面的信息,如心肌梗死、卒中或由于血管事件死亡。各个独立研究者和药厂为本研究提供了有关随机化的病人数目、血管事件的数目以及每个随机化小组中随访的人时(Person time)等信息。结果:在与安慰剂对比的试验中,选择性COX-2抑制剂使严重血管事件发生率增加42%(1.2%/年比0.9%/年;率比1.42,95%可信区间1.13～1.78;P=0.005);不同的选择性 COX-2抑制剂之间没有显著性差异。这主要归因于心肌梗死的风险增加(0.6%/年比0.3%/年;1.86,1.33～2.59;P=0.0003),在其他血管性事件上没有明显的区别。在为时至少1年的试验中(平均2.7年),血管事件的率比是1.45(1.12～1.89;P=0.005)。总的来说,严重血管事件的发生率在选择性 COX-2抑制剂和任何传统 NSAID 之间没有差异(1.0%/年比0.9%/年;1.16,0.97～1.38;P=0.1)。然而,在选择性 COX-2抑制剂与萘普生对比的试验(1.57,1.21～2.03)和选择性COX-2抑制剂与非萘普生类 NSAIDs 相比较的试验之间(0.88,O.69～1.12),我们发现了统计学差异。与安慰剂比较血管事件的总体比率如下:萘普生0.92(0.67～1.26),布洛芬1.51(0.96～2.37),双氯芬酸1.63(1.12～2.37)。结论:选择性 COX-2抑制剂可以中等度增加血管事件的风险性,大剂量布洛芬和双氯芬酸同样具有此作用,但大剂量萘普生不明显增加血管事件的风险性。
PURPOSE: To evaluate the risks of selective cyclooxygenase 2 (COX-2) inhibitors and traditional non-steroidal anti-inflammatory drugs (NSMDs) in the development of vascular events. Design: A meta-analysis of tabular data from published and unpublished randomized trials to indirectly assess the role of traditional NSAIDs. Source: Data from Medline and Embase respectively (January 1966 to April 2005); Food and Drug Administration records; and data from Novartis, Pfizer and Merck. RETRIEVAL METHODS: A randomized trial of either a selective COX-2 inhibitor versus placebo or a selective COX-2 inhibitor versus a traditional NSAID was included in the study. Duration of dosing At least 4 weeks; Contains information on a serious vascular event, such as myocardial infarction, stroke, or death due to a vascular event. Independent researchers and pharmaceutical companies provided the study with information on the number of patients randomized, the number of vascular events, and the time of follow-up (Person time) in each randomized cohort. RESULTS: Selective COX-2 inhibitors increased the incidence of major vascular events by 42% (1.2% / year vs 0.9% / year; rate 1.42, 95% confidence interval 1.13-1.78 ; P = 0.005); There was no significant difference between the different selective COX-2 inhibitors. This is mainly due to an increased risk of MI (0.6% / year vs 0.3% / year; 1.86, 1.33 to 2.59; P = 0.0003) with no significant difference in other vascular events. The rate of vascular events was 1.45 (1.12 to 1.89; P = 0.005) in the trial lasting for at least 1 year (an average of 2.7 years). Overall, the incidence of serious vascular events did not differ between the selective COX-2 inhibitor and any conventional NSAIDs (1.0% / year vs 0.9% / year; 1.16, 0.97 to 1.38; P = 0.1). However, between trials comparing selective COX-2 inhibitors to naproxen (1.57, 1.21 to 2.03) and between selective COX-2 inhibitors and non-naproxen NSAIDs (0.88, 69 ~ 1.12), we found a statistically significant difference. The overall rates of vascular events compared with placebo were as follows: naproxen 0.92 (0.67-1.26), ibuprofen 1.51 (0.96-2.37), diclofenac 1.63 (1.12-2.37). CONCLUSIONS: Selective COX-2 inhibitors moderately increase the risk of vascular events. High-dose ibuprofen and diclofenac also have this effect, but high-dose naproxen did not significantly increase the risk of vascular events.