Hippisley-Cox Julia, Coupland Carol
Institution 13th floor, Tower Building, University Park, Nottingham NG2 7RD.
BMJ. 2005 Jun 11;330(7504):1366. doi: 10.1136/bmj.330.7504.1366.
To determine the comparative risk of myocardial infarction in patients taking cyclo-oxygenase-2 and other non-steroidal anti-inflammatory drugs (NSAIDs) in primary care between 2000 and 2004; to determine these risks in patients with and without pre-existing coronary heart disease and in those taking and not taking aspirin.
Nested case-control study.
367 general practices contributing to the UK QRESEARCH database and spread throughout every strategic health authority and health board in England, Wales, and Scotland.
9218 cases with a first ever diagnosis of myocardial infarction during the four year study period; 86 349 controls matched for age, calendar year, sex, and practice.
Unadjusted and adjusted odds ratios with 95% confidence intervals for myocardial infarction associated with rofecoxib, celecoxib, naproxen, ibuprofen, diclofenac, and other selective and non-selective NSAIDS. Odds ratios were adjusted for smoking status, comorbidity, deprivation, and use of statins, aspirin, and antidepressants.
A significantly increased risk of myocardial infarction was associated with current use of rofecoxib (adjusted odds ratio 1.32, 95% confidence interval 1.09 to 1.61) compared with no use within the previous three years; with current use of diclofenac (1.55, 1.39 to 1.72); and with current use of ibuprofen (1.24, 1.11 to 1.39). Increased risks were associated with the other selective NSAIDs, with naproxen, and with non-selective NSAIDs; these risks were significant at < 0.05 rather than < 0.01 for current use but significant at < 0.01 in the tests for trend. No significant interactions occurred between any of the NSAIDs and either aspirin or coronary heart disease.
These results suggest an increased risk of myocardial infarction associated with current use of rofecoxib, diclofenac, and ibuprofen despite adjustment for many potential confounders. No evidence was found to support a reduction in risk of myocardial infarction associated with current use of naproxen. This is an observational study and may be subject to residual confounding that cannot be fully corrected for. However, enough concerns may exist to warrant a reconsideration of the cardiovascular safety of all NSAIDs.
确定2000年至2004年在基层医疗中服用环氧化酶-2和其他非甾体抗炎药（NSAIDs）的患者发生心肌梗死的相对风险；确定在有和没有冠心病的患者以及服用和未服用阿司匹林的患者中的这些风险。
巢式病例对照研究。
367家参与英国QRESEARCH数据库的全科诊所，分布在英格兰、威尔士和苏格兰的每个战略卫生管理局和卫生委员会。
在四年研究期间首次诊断为心肌梗死的9218例患者；86349例对照，按年龄、日历年、性别和诊所进行匹配。
与罗非昔布、塞来昔布、萘普生、布洛芬、双氯芬酸以及其他选择性和非选择性NSAIDs相关的心肌梗死的未调整和调整后的比值比及95%置信区间。比值比根据吸烟状况、合并症、贫困程度以及他汀类药物、阿司匹林和抗抑郁药的使用情况进行调整。
与过去三年未使用相比，当前使用罗非昔布（调整后的比值比为1.32，95%置信区间为1.09至1.61）、双氯芬酸（1.55，1.39至1.72）和布洛芬（1.24，1.11至1.39）与心肌梗死风险显著增加相关。其他选择性NSAIDs、萘普生和非选择性NSAIDs也与风险增加相关；这些风险在当前使用时在<0.05而非<0.01时具有统计学意义，但在趋势检验中在<0.01时具有统计学意义。任何NSAIDs与阿司匹林或冠心病之间均未发生显著相互作用。
这些结果表明，尽管对许多潜在混杂因素进行了调整，但当前使用罗非昔布、双氯芬酸和布洛芬与心肌梗死风险增加相关。未发现证据支持当前使用萘普生可降低心肌梗死风险。这是一项观察性研究，可能存在无法完全校正的残余混杂因素。然而，可能存在足够多的担忧，值得重新考虑所有NSAIDs的心血管安全性。
