Cardiovascular events associated with rofecoxib: final analysis of the APPROVe trial
Cardiovascular events associated with rofecoxib: final analysis of the APPROVe trial
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DOI：
10.1016/s0140-6736(08)61490-7
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发表时间：
2008-11-15
期刊：
影响因子：
168.9
通讯作者：
DeMets, David L.
中科院分区：
文献类型：
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作者：
Baron, John A.;Sandler, Robert S.;DeMets, David L.
背景在一些临床试验中，选择性抑制环氧合酶-2与心血管事件风险增加有关。万络预防腺瘤性息肉（APPROVe）研究评估了环氧化酶-2抑制剂罗非昔布（25 mg）治疗3年对大肠肿瘤性息肉复发的影响。我们报告的长期随访的参与者在trial.Methods的APPROVe研究的心血管结局是一个多中心，随机，安慰剂对照，双盲试验。在2000年和2001年期间，在全球108个中心招募了2587例有结直肠腺瘤病史的患者。在治疗期间和接下来的14天内，对参与者的不良事件进行了随访。然而，在因心血管毒性而提前终止治疗后，我们试图在停止研究治疗后对所有随机化患者进行至少1年的随访。外部委员会对潜在严重心血管事件进行盲态评估。分析的重点是非致死性心肌梗死、非致死性卒中以及心血管、出血和不明原因死亡的合并发生率（抗血小板试验者协作组[APTC]合并终点）。我们使用考克斯比例风险回归计算终点风险比。该研究在ClinicalTrials.gov注册，编号NCT 0282386。结果我们从84%的参与者中获得了延长的治疗后心血管随访数据，并从95%延长了死亡率随访。罗非昔布组共有59人达到APTC终点，安慰剂组有34人达到APTC终点（风险比为1。79，95%CI 1。17-2-73; p=0.006）。在停止治疗后的第一年，APTC终点的风险无显著增加。APTC风险比并没有随时间发生实质性变化。解释使用罗非昔布与APTC事件发生率增加相关。研究数据与停止治疗后持续一年的早期风险增加相一致。
Background Selective inhibition of cyclo-oxygenase-2 has been associated with an increased risk of cardiovascular events in several clinical trials. The Adenomatous Polyp Prevention on Vioxx (APPROVe) study assessed the effect of 3-year treatment with a cyclo-oxygenase-2 inhibitor, rofecoxib (25 mg), on recurrence of neoplastic polyps of the large bowel. We report the cardiovascular outcomes of a long-term follow-up of participants in the trial.Methods The APPROVe study is a multicentre, randomised, placebo-controlled, double-blind trial. 2587 patients with a history of colorectal adenomas were recruited at 108 centres worldwide during 2000 and 2001. Participants were followed for adverse events while on treatment and during the following 14 days. However, after early termination of treatment because of cardiovascular toxicity, we attempted to follow tip all randomised patients for at least 1 year after stopping study treatment. External committees blindly assessed potential serious cardiovascular events. The focus of the analysis was the combined incidence of non-fatal myocardial infarction, non-fatal stroke, and death from cardiovascular, haemorrhagic, and unknown causes (Antiplatelet Trialists' Collaboration [APTC] combined endpoint). We used Cox proportional hazards regression to calculate endpoint hazard ratios. The study is registered with ClinicalTrials.gov, number NCT0282386.Findings We obtained extended post-treatment cardiovascular follow-up data from 84% of participants, and extended mortality follow-up from 95%. In total, 59 individuals had an APTC endpoint in the rofecoxib group and 34 in the placebo group (hazard ratio 1. 79, 95% CI 1. 17-2-73; p=0.006). In the first year after cessation of treatment, there was a non-significant increase in the risks of APTC endpoints. The APTC hazard ratio did not substantially change over time.Interpretation Use of rofecoxib is associated with increased rates of APTC events. Study data are compatible with an early increase in risk that persists for one year after stopping treatment.Funding Merck Research Laboratories.