Cardiovascular outcomes with etoricoxib and diclofenac in patients with osteoarthritis and rheumatoid arthritis in the Multinational Etoricoxib and Diclofenac Arthritis Long-term (MEDAL) programme: a randomised comparison
Cardiovascular outcomes with etoricoxib and diclofenac in patients with osteoarthritis and rheumatoid arthritis in the Multinational Etoricoxib and Diclofenac Arthritis Long-term (MEDAL) programme: a randomised comparison
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DOI：
10.1016/s0140-6736(06)69666-9
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发表时间：
2006-11-18
期刊：
影响因子：
168.9
通讯作者：
Laine, Loren
中科院分区：
文献类型：
--
作者：
Cannon, Christopher P.;Curtis, Sean P.;Laine, Loren
背景在安慰剂对照试验中，环氧合酶-2（考克斯-2）选择性抑制剂与血栓性心血管事件风险增加相关，但尚未报道主要目的是评估这些药物与传统非甾体抗炎药（NSAID）相比的相对心血管风险的临床试验。MEDAL计划的目的是提供一个精确的估计血栓性心血管事件与考克斯-2选择性抑制剂依托考昔与传统的NSAID双氯芬酸。方法我们设计了一个预先指定的汇总分析数据从三个试验中，骨关节炎或类风湿性关节炎患者被随机分配到依托考昔（60毫克或90毫克，每天）或双氯芬酸（150毫克，每天）。主要假设表明依托考昔不劣于双氯芬酸，定义为符合方案分析中血栓性心血管事件风险比的95% CI上限小于1.30。还进行了意向治疗分析，以评估结果的一致性。这些试验在http：//www. clinicaltrials.gov 平均治疗持续时间为18个月（SD 11.8）。依托考昔组和双氯芬酸组分别有320例和323例患者发生血栓性心血管事件，事件发生率分别为1.24和1.30/100患者-年，依托考昔与双氯芬酸相比的风险比为0.95（95% CI 0.81 - 1.11）。上消化道临床事件发生率（穿孔、出血、梗阻、溃疡）的发生率低于双氯芬酸（0.67 vs 0.97/100患者年;风险比0.69 [0.57 - 0.83]），但依托考昔的复杂上消化道事件发生率相似在关节炎患者中，接受依托考昔治疗的血栓性心血管事件的解释率与长期使用这些药物的双氯芬酸患者相似。
Background Cyclo-oxygenase-2 (COX-2) selective inhibitors have been associated with an increased risk of thrombotic cardiovascular events in placebo-controlled trials, but no clinical trial has been reported with the primary aim of assessing relative cardiovascular risk of these drugs compared with traditional non-steroidal anti-inflammatory drugs (NSAIDs). The MEDAL programme was designed to provide a precise estimate of thrombotic cardiovascular events with the COX-2 selective inhibitor etoricoxib versus the traditional NSAID diclofenac.Methods We designed a prespecified pooled analysis of data from three trials in which patients with osteoarthritis or rheumatoid arthritis were randomly assigned to etoricoxib (60 mg or 90 mg daily) or diclofenac (150 mg daily). The primary hypothesis stated that etoricoxib is not inferior to diclofenac, defined as an upper boundary of less than 1.30 for the 95% CI of the hazard ratio for thrombotic cardiovascular events in the per-protocol analysis. Intention-to-treat analyses were also done to assess consistency of results. These trials are registered at http://www. clinicaltrials.gov with the numbers NCT00092703, NCT00092742, and NCT00250445.Findings 34701 patients (24913 with osteoarthritis and 9787 with rheumatoid arthritis) were enrolled. Average treatment duration was 18 months (SD 11.8). 320 patients in the etoricoxib group and 323 in the diclofenac group had thrombotic cardiovascular events, yielding event rates of 1.24 and 1.30 per 100 patient-years and a hazard ratio of 0.95 (95% CI 0.81-1.11) for etoricoxib compared with diclofenac. Rates of upper gastrointestinal clinical events (perforation, bleeding, obstruction, ulcer) were lower with etoricoxib than with diclofenac (0.67 vs 0.97 per 100 patient-years; hazard ratio 0.69 [0.57-0.83]), but the rates of complicated upper gastrointestinal events were similar for etoricoxib (0.30) and diclofenac (0.32).Interpretation Rates of thrombotic cardiovascular events in patients with arthritis on etoricoxib are similar to those in patients on diclofenac with long-term use of these drugs.