Krötz Florian, Struthmann Lena
Cardiology, Medical Policlinic, University Hospital Munich, Ludwig-Maximilians-University, Ziemssenstr. 1, 80336 München, Germany.
Cardiovasc Hematol Disord Drug Targets. 2010 Mar;10(1):53-65. doi: 10.2174/187152910790780041.
The popular over-the counter analgesic drug diclofenac has recently been associated with increased rates of myocardial infarction among patients with cardiovascular risk as well as among healthy populations. Although other traditional non-steroidal anti-inflammatory drugs (tNSAID) have also been accused to exert this risk, literature data at present gives reason to believe that the hazard of myocardial infarction is mainly associated with diclofenac. Large retrospective analyses of clinical data have repeatedly shown that diclofenac, similar as some selective COX-2 inhibitors, increases the propensity to experience adverse cardiovascular and atherothrombotic events. These associations cannot be explained with the deteriorating effect of NSAID on arterial hypertension, as the statistical associations only have been found conclusively for diclofenac and not for other tNSAID. The reasons for this novel side-effect of diclofenac may be based on the specific pharmacology of diclofenac, which, similar to selective COX-2 inhibitors, alters vascular levels of platelet active prostaglandins in a way that favours arterial thrombosis. In this review, we summarize the clinical evidence about adverse atherothrombotic events associated with diclofenac and dissect the pharmacological reasons beyond this phenomenon in comparison to other tNSAID.
常用的非处方镇痛药双氯芬酸最近被发现与心血管疾病风险患者以及健康人群中心肌梗死发生率升高有关。尽管其他传统非甾体抗炎药(tNSAID)也被指责存在这种风险,但目前的文献数据表明,心肌梗死风险主要与双氯芬酸有关。对临床数据的大型回顾性分析反复表明,双氯芬酸与某些选择性环氧化酶-2(COX-2)抑制剂类似,会增加发生不良心血管和动脉粥样血栓形成事件的倾向。这些关联无法用非甾体抗炎药对动脉高血压的恶化作用来解释,因为仅在双氯芬酸中明确发现了统计学关联,而在其他tNSAID中未发现。双氯芬酸这种新副作用的原因可能基于其特定的药理学特性,与选择性COX-2抑制剂类似,它会以一种有利于动脉血栓形成的方式改变血小板活性前列腺素的血管水平。在本综述中,我们总结了与双氯芬酸相关的不良动脉粥样血栓形成事件的临床证据,并与其他tNSAID相比剖析了这一现象背后的药理学原因。