Huang Weng-Foung, Hsiao Fei-Yuan, Wen Yu-Wen, Tsai Yi-Wen
Institute of Health and Welfare Policy, National Yang-Ming University, Taipei, Taiwan.
Clin Ther. 2006 Nov;28(11):1827-36. doi: 10.1016/j.clinthera.2006.11.009.
Serious cardiovascular events (CVEs) have been linked to the use of cyclooxygenase (COX)-2 inhibitors, a category of selective NSAIDs. However, few studies are available that have compared the risk for CVEs between COX-2 inhibitors and nonselective NSAIDs in adults undergoing long-term treatment.
The present study assessed (1) whether long-term use of nonselective NSAIDs (etodolac, nabumetone, ibuprofen, or naproxen) is associated with an increased risk for treatment-related CVEs (acute myocardial infarction [AMI], angina, cerebrovascular attack [CVA], and/or transient ischemic attack [TIA]) compared with long-term use of celecoxib and (2) which factors are associated with the risk for treatment-related CVEs in long-term users of nonselective NSAIDs in Taiwan.
This population-based analysis used data from the Taiwanese Bureau of National Health Insurance (Taipei, Taiwan) database. Eligible patients were aged > or = 18 years and had been receiving etodolac, nabumetone, ibuprofen, naproxen, or celecoxib for > or = 180 days between January 1, 2001, and December 31, 2003. The primary outcomes measure was the prevalence of serious CVEs (AMI, angina, CVA, and/or TIA requiring hospitalization) after initiation of treatment. Analyses were performed on data from all eligible patients; person-time exposures to the drugs and hazard ratios (HRs) were calculated to determine the risk for CVEs with long-term use.
A total of 16,326 patients (8166 men, 8160 women; mean [SD] age, 61.83 [20.23] years) who had received long-term treatment with etodolac (2014 [12.34%]), nabumetone (2262 [13.86%]), ibuprofen (5239 [32.09%]), naproxen (3049 [18.68%]), or celecoxib (3762 [23.04%]) were identified. The overall prevalences of AMI, angina, CVA, and TIA were higher in long-term users with a history of cardiovascular disease (CVD) than in those without (AMI, 4.76% vs 0.99%; angina, 4.11% vs 0.43%; CVA, 7.74% vs 1.51%; and TIA, 4.03% vs 0.52%) (all, P < 0.01). The HRs for AMI, angina, CVA, and TIA were not significantly different between the NSAID and celecoxib groups. History of CVD played a significant role in recurrence during the period studied; the HRs (95% CIs) were 2.29 (1.22-4.32) for AMI, 6.19 (3.56-10.78) for angina, 3.56 (2.80-4.52) for CVA, and 6.60 (3.72-11.73) for TIA. Preexisting medical conditions (hypertension, dyslipidemia, diabetes mellitus, congestive heart failure, chronic renal disease) also significantly affected the risk for CVEs.
In this cohort study of long-term (> or = 180 days) use of NSAIDs in Taiwanese adults, no significant differences in the risk for treatment-related CVEs were observed between groups prescribed 1 of 4 nonselective NSAIDs (etodolac, nabumetone, ibuprofen, or naproxen) or celecoxib. History of CVD was the most significant determinant of CVE risk. Patients with preexisting medical conditions appeared to have a significantly higher risk for CVEs associated with the use of NSAIDs and celecoxib compared with patients without these conditions.
严重心血管事件（CVEs）与环氧化酶（COX）-2抑制剂的使用有关，COX-2抑制剂是一类选择性非甾体抗炎药（NSAIDs）。然而，很少有研究比较长期治疗的成年人中COX-2抑制剂与非选择性NSAIDs之间发生CVEs的风险。
本研究评估了（1）与长期使用塞来昔布相比，长期使用非选择性NSAIDs（依托度酸、萘丁美酮、布洛芬或萘普生）是否与治疗相关的CVEs（急性心肌梗死[AMI]、心绞痛、脑血管意外[CVA]和/或短暂性脑缺血发作[TIA]）风险增加有关，以及（2）台湾长期使用非选择性NSAIDs的患者中，哪些因素与治疗相关的CVEs风险有关。
这项基于人群的分析使用了台湾国民健康保险局（台北，台湾）数据库中的数据。符合条件的患者年龄≥18岁，在2001年1月1日至2003年12月31日期间接受依托度酸、萘丁美酮、布洛芬、萘普生或塞来昔布治疗≥180天。主要结局指标是治疗开始后严重CVEs（需要住院治疗的AMI、心绞痛、CVA和/或TIA）的患病率。对所有符合条件的患者的数据进行分析；计算药物的人时暴露量和风险比（HRs）以确定长期使用CVEs的风险。
共识别出16326例患者（8166例男性，8160例女性；平均[标准差]年龄，61.83[20.23]岁），他们接受了依托度酸（2014例[12.34%]）、萘丁美酮（2262例[13.86%]）、布洛芬（5239例[32.09%]）、萘普生（3049例[18.68%]）或塞来昔布（3762例[23.04%]）的长期治疗。有心血管疾病（CVD）病史的长期使用者中，AMI、心绞痛、CVA和TIA的总体患病率高于无CVD病史者（AMI，4.76%对0.99%；心绞痛，4.11%对0.43%；CVA，7.74%对1.51%；TIA，4.03%对0.52%）（均P<0.01）。NSAIDs组和塞来昔布组之间AMI、心绞痛、CVA和TIA的HRs无显著差异。CVD病史在研究期间的复发中起重要作用；AMI的HRs（95%CI）为2.29（1.22 - 4.32），心绞痛为6.19（3.56 - 10.78），CVA为3.56（2.80 - 4.52），TIA为6.60（3.72 - 11.73）。既往存在的疾病（高血压、血脂异常、糖尿病、充血性心力衰竭、慢性肾病）也显著影响CVEs的风险。
在这项对台湾成年人长期（≥180天）使用NSAIDs的队列研究中，在开具4种非选择性NSAIDs（依托度酸、萘丁美酮、布洛芬或萘普生）之一或塞来昔布的组之间，未观察到治疗相关CVEs风险的显著差异。CVD病史是CVE风险的最重要决定因素。与无这些疾病的患者相比，既往存在疾病的患者使用NSAIDs和塞来昔布相关的CVEs风险似乎显著更高。
