Gentofte University Hospital, Department of Cardiology, Hellerup, Denmark.
Expert Opin Drug Saf. 2010 Nov;9(6):893-903. doi: 10.1517/14740338.2010.501331.
Studies have raised concern on the cardiovascular safety of NSAIDs. We studied safety of NSAID therapy in a nationwide cohort of healthy individuals.
This is a review of the literature regarding cardiovascular safety of NSAIDs with special focus on the few studies investigating healthy individuals.
Due to a high frequency of gastrointestinal complications related to NSAID treatment a new generation of NSAID, called the selective COX-2 inhibitors, were developed in order to use the beneficial pain-relieving effect of NSAIDs without the COX-1 related risk of gastrointestinal bleeding. However, the selective COX-2 inhibitor rofecoxib was withdrawn from the market in 2004 after studies had documented an increased risk of myocardial infarction related to this drug. Focus also turned to the traditional NSAIDs and found similar results for some of the older drugs, especially diclofenac and high-dose ibuprofen. Most interventional studies have not been designed specifically to evaluate the cardiovascular safety of NSAIDs and no studies have previously investigated the relationship between NSAID treatment and cardiovascular risk in healthy individuals. Overall, evidence regarding the selective COX-2 inhibitors' cardiovascular risk profile (mostly thrombo-embolic events) is derived from the clinical trials whereas results on the traditional NSAIDs are based on observational studies and meta-analyses. Importantly, some of the randomized trials comparing COX-2 inhibitors with traditional NSAIDs did not show a difference in cardiovascular risk and it cannot be denied that the traditional NSAIDs are characterized by a different cardiovascular risk-profile than the COX-2 inhibitors. A recent cohort study among one million healthy people showed that the selective COX-2 inhibitors as well as diclofenac are associated with an increased risk of death or myocardial infarction. This was further underlined by a dose-response relationship.
Individual NSAIDs have different cardiovascular safety that needs to be considered when choosing appropriate treatment. In particular, rofecoxib and diclofenac were associated with increased cardiovascular mortality and morbidity and should be used with caution in most individuals. This notion is also valid for healthy individuals and underlines the importance of critical use of NSAID therapy in the general population and also that over-the-counter retail of NSAIDs should be reassessed.
研究已经对 NSAIDs 的心血管安全性提出了关注。我们在一个全国性的健康人群队列中研究了 NSAID 治疗的安全性。
这是一篇关于 NSAIDs 心血管安全性的文献综述，特别关注了少数研究健康人群的研究。
由于与 NSAID 治疗相关的胃肠道并发症的高频率，新一代 NSAID，称为选择性 COX-2 抑制剂，被开发出来，以便在不使用 COX-1 相关的胃肠道出血风险的情况下利用 NSAIDs 的有益的止痛效果。然而，选择性 COX-2 抑制剂罗非昔布在 2004 年被撤出市场，因为研究已经记录了与这种药物相关的心肌梗死风险增加。人们的注意力也转向了传统的 NSAIDs，并对一些较老的药物发现了类似的结果，特别是双氯芬酸和高剂量布洛芬。大多数干预性研究并非专门设计用于评估 NSAIDs 的心血管安全性，也没有研究以前调查过 NSAID 治疗与健康人群心血管风险之间的关系。总体而言，关于选择性 COX-2 抑制剂心血管风险概况（主要是血栓栓塞事件）的证据来自临床试验，而关于传统 NSAIDs 的结果则基于观察性研究和荟萃分析。重要的是，一些比较 COX-2 抑制剂与传统 NSAIDs 的心血管风险的随机试验没有显示出心血管风险的差异，也不能否认传统 NSAIDs 的心血管风险特征与 COX-2 抑制剂不同。一项针对一百万人的队列研究表明，选择性 COX-2 抑制剂和双氯芬酸与死亡或心肌梗死的风险增加有关。这种情况还进一步被剂量-反应关系所强调。
个体 NSAIDs 具有不同的心血管安全性，在选择合适的治疗方法时需要考虑。特别是罗非昔布和双氯芬酸与心血管死亡率和发病率增加有关，在大多数患者中应谨慎使用。这一概念也适用于健康人群，强调了在普通人群中谨慎使用 NSAID 治疗的重要性，也需要重新评估 NSAIDs 的非处方零售。
