Risk of cardiovascular events associated with selective COX-2 inhibitors
Risk of cardiovascular events associated with selective COX-2 inhibitors
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DOI：
10.1001/jama.286.8.954
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发表时间：
2001-08-22
影响因子：
120.7
通讯作者：
Topol, EJ
中科院分区：
文献类型：
--
作者：
Mukherjee, D;Nissen, SE;Topol, EJ
动脉粥样硬化是一个具有炎症特征的过程，选择性环氧合酶2（考克斯-2）抑制剂可能通过抑制炎症而具有潜在的抗动脉粥样硬化作用。然而，通过减少血管舒张和抗聚集前列环素的产生，考克斯-2拮抗剂可能导致血栓前活性增加。为了明确考克斯-2抑制剂用于无冠状动脉疾病患者关节炎和肌肉骨骼疼痛时的心血管效应，我们进行了MEDLINE检索，以确定1998年至2001年2月期间发表的所有关于使用考克斯-2抑制剂的英文文章。我们还审查了制药公司提交给美国食品药品监督管理局的相关资料，检索到2项主要的随机试验，万络胃肠道结局研究（VIGOR; 8076例患者）和塞来昔布长期关节炎安全性研究（CLASS; 8059例患者），以及2项各约1000例患者的小型试验。VIGOR的结果显示，罗非昔布治疗与纳洛芬治疗相比，发生经证实的血栓性心血管事件（心肌梗死、不稳定型心绞痛、心脏血栓、心脏骤停复苏、猝死或不明原因死亡、缺血性卒中和短暂性脑缺血发作）的相对风险为2.38（95%置信区间1.39-4.00; P= 0.002）。在CLASS中，塞来昔布和非甾体类抗炎药之间的心血管事件（心肌梗死、卒中和死亡）发生率无显著差异。最近一项荟萃分析显示，在一级预防试验中，考克斯-2抑制剂组的年心肌梗死发生率在VIGOR和CLASS中均显著高于安慰剂组（0.52%）：罗非昔布组为0.74%（与荟萃分析的安慰剂组相比，P= 0.04），塞来昔布组为0.80%（与荟萃分析的安慰剂组相比，P= 0.02）。现有数据对考克斯-2抑制剂的心血管事件风险提出了警示。进一步的前瞻性试验评价可以表征和确定风险的大小。
Atherosclerosis is a process with inflammatory features and selective cyclooxygenase 2 (COX-2) inhibitors may potentially have antiatherogenic effects by virtue of inhibiting inflammation. However, by decreasing vasodilatory and antiaggregatory prostacyclin production, COX-2 antagonists may lead to increased prothrombotic activity. To define the cardiovascular effects of COX-2 inhibitors when used for arthritis and musculoskeletal pain in patients without coronary artery disease, we performed a MEDLINE search to identify all English-language articles on use of COX-2 inhibitors published between 1998 and February 2001. We also reviewed relevant submissions to the US Food and Drug Administration by pharmaceutical companies.Our search yielded 2 major randomized trials, the Vioxx Gastrointestinal Outcomes Research Study (VIGOR; 8076 patients) and the Celecoxib Longterm Arthritis Safety Study (CLASS; 8059 patients), as well as 2 smaller trials with approximately 1000 patients each. The results from VIGOR showed that the relative risk of developing a confirmed adjudicated thrombotic cardiovascular event (myocardial infarction, unstable angina, cardiac thrombus, resuscitated cardiac arrest, sudden or unexplained death, ischemic stroke, and transient ischemic attacks) with rofecoxib treatment compared with naproxen was 2.38 (95% confidence interval 1.39-4.00; P=.002). There was no significant difference in cardiovascular event (myocardial infarction, stroke, and death) rates between celecoxib and nonsteroidal anti-inflammatory agents in CLASS. The annualized myocardial infarction rates for COX-2 inhibitors in both VIGOR and CLASS were significantly higher than that in the placebo group of a recent meta-analysis of 23407 patients in primary prevention trials (0.52%):0.74% with rofecoxib (P=.04 compared with the placebo group of the meta-analysis) and 0.80% with celecoxib (P=.02 compared with the placebo group of the meta-analysis).The available data raise a cautionary flag about the risk of cardiovascular events with COX-2 inhibitors. Further prospective trial evaluation may characterize and determine the magnitude of the risk.