Thöne Kathrin, Kollhorst Bianca, Schink Tania
Leibniz Institute for Prevention Research and Epidemiology, BIPS, Bremen, Germany.
University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany.
Drugs Real World Outcomes. 2017 Sep;4(3):127-137. doi: 10.1007/s40801-017-0113-x.
Use of non-steroidal anti-inflammatory drugs (NSAIDs) has been associated with an increased relative risk of acute myocardial infarction (AMI), but the label warnings refer particularly to patients with cardiovascular risk factors. The magnitude of relative AMI risk for patients with and without cardiovascular risk factors varies between studies depending on the drugs and doses studied.
The aim of our study was to estimate population-based relative AMI risks for individual and widely used NSAIDs, for a cumulative amount of NSAID use, and for patients with and without a prior history of cardiovascular risk factors.
Based on data from the German Pharmacoepidemiological Research Database (GePaRD) of about 17 million insurance members from four statutory health insurance providers, for the years 2004-2009, a nested case-control study was conducted within a cohort of 3,476,931 new NSAID users classified into current, recent, or past users. Up to 100 controls were matched to each case by age, sex, and length of follow-up using risk set sampling. Multivariable conditional logistic regression was applied to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Duration of NSAID use was calculated by the cumulative amount of dispensed defined daily doses (DDDs), and stratified analyses were conducted for potential effect modifiers.
Overall, 17,236 AMI cases were matched to 1,714,006 controls. Elevated relative AMI risks were seen for current users of fixed combinations of diclofenac with misoprostol (OR 1.76, 95% CI 1.26-2.45), indometacin (1.69, 1.22-2.35), ibuprofen (1.54, 1.43-1.65), etoricoxib (1.52, 1.24-1.87), and diclofenac (1.43, 1.34-1.52) compared with past use. A low cumulative NSAID amount was associated with a higher relative AMI risk for ibuprofen, diclofenac, and indometacin. The relative risk associated with current use of diclofenac, fixed combinations of diclofenac with misoprostol, etoricoxib, and ibuprofen was highest in the younger age group (<60 years) and similar for patients with or without major cardiovascular risk factors.
Relative AMI risk estimates differed among the 15 investigated individual NSAIDs. Diclofenac and ibuprofen, the most frequently used NSAIDs, were associated with a 40-50% increased relative risk of AMI, even for low cumulative NSAID amounts. The relative AMI risk in patients with and without cardiovascular risk factors was similarly elevated.
使用非甾体抗炎药（NSAIDs）与急性心肌梗死（AMI）的相对风险增加相关，但标签警告特别针对有心血管危险因素的患者。根据所研究的药物和剂量不同，有和没有心血管危险因素的患者发生AMI的相对风险在不同研究中有所差异。
我们研究的目的是估计基于人群的个体及广泛使用的NSAIDs、NSAIDs累积使用量以及有和没有心血管危险因素既往史患者发生AMI的相对风险。
基于德国药物流行病学研究数据库（GePaRD）中来自四家法定健康保险机构的约1700万保险成员的数据，对2004年至2009年期间3476931名新的NSAIDs使用者队列进行了巢式病例对照研究，这些使用者被分类为当前使用者、近期使用者或既往使用者。使用风险集抽样方法，按照年龄、性别和随访时间长度为每个病例匹配多达100名对照。应用多变量条件逻辑回归来估计比值比（ORs）和95%置信区间（CIs）。NSAIDs使用持续时间通过累积分配的限定日剂量（DDDs）计算，并针对潜在效应修饰因素进行分层分析。
总体而言，17236例AMI病例与1714006名对照进行了匹配。与既往使用相比，双氯芬酸与米索前列醇固定组合的当前使用者（OR 1.76，95% CI 1.26 - 2.45）、吲哚美辛（1.69，1.22 - 2.35）、布洛芬（1.54，1.43 - 1.65）、依托考昔（1.52，1.24 - 1.87）和双氯芬酸（1.43，1.34 - 1.52）的AMI相对风险升高。低累积NSAIDs量与布洛芬、双氯芬酸和吲哚美辛的较高AMI相对风险相关。双氯芬酸、双氯芬酸与米索前列醇固定组合、依托考昔和布洛芬当前使用相关的相对风险在较年轻年龄组（<60岁）中最高，有或没有主要心血管危险因素的患者相似。
在所研究的15种个体NSAIDs中，AMI相对风险估计值有所不同。双氯芬酸和布洛芬是最常用的NSAIDs，即使累积NSAIDs量较低，它们与AMI相对风险增加40% - 50%相关。有和没有心血管危险因素的患者发生AMI的相对风险同样升高。
