Hellstrom H R
Med Hypotheses. 2007;69(1):83-9. doi: 10.1016/j.mehy.2006.11.027. Epub 2007 Jan 12.
In this communication, a pathogenetic mechanism for COX-2 inhibitor (coxib)-induced cardiovascular events, especially myocardial infarction, will be discussed. This mechanism is proposed to be useful in structuring medical testimony in rofecoxib trials, and specific principles for separating rofecoxib-induced infarctions from the overall group of rofecoxib-related infarctions will be outlined. The proposed mechanism is based on the principles of the altered homeostatic theory, whose basic positions will be summarized. Coxib-induced infarctions apparently have been considered to be "special" infarctions because they generally are attributed to thromboxane rather than to dyslipidemia. However, it is asserted that coxib-induced infarctions basically are "regular" infarctions because the risk of thromboxane is basically the same as the risk of multiple and diverse "regular" risk factors. Both coxibs and "regular" risk factors are considered to express thrombosis/vasoconstriction, and it is this expression which makes coxib-induced infarctions basically "regular" infarctions. Thrombosis/vasoconstriction is crucial to the induction of myocardial infarction; thrombosis is the accepted and spasm (of resistance vessels) is a proposed mechanism for infarction. It also is asserted that coxib-induced infarctions have a significant load of "regular" risk factors, and that the risk of coxibs adds to the risk of "regular" risk factors. The combination of a significant load of "regular" risk factors plus the risk of coxibs is considered necessary to cause a coxib-induced infarction. It will be difficult to separate out with surety many, if not most, cases of rofecoxib-induced infarctions; this is because of the difficulty in assessing the risk imposed by "regular" risk factors vis-à-vis the risk of rofecoxib, and specific problems in separation will be discussed. However, reasonably, infarctions with a short time-to-event tend to be rofecoxib-induced; infarctions which closely follow a new risk factor, as loss of spouse or stress, would rather automatically be attributed to the new risk factor. It then follows that infarctions with a long time-to-event tend to be non-rofecoxib-induced. Additionally, and contrary to past practice, infarctions cannot be designated as non-rofecoxib-induced infarctions because of the presence of a significant load of "regular" risk factors; after all, rofecoxib-induced infarctions reasonably are associated with a significant load of such risk factors.
在本交流中，将讨论环氧化酶-2抑制剂（昔布类）诱发心血管事件尤其是心肌梗死的发病机制。该机制被认为有助于在罗非昔布试验中构建医学证词，并将概述从所有罗非昔布相关梗死中区分出罗非昔布诱发梗死的具体原则。所提出的机制基于内稳态理论改变的原则，其基本观点将予以总结。昔布类诱发的梗死显然被视为“特殊”梗死，因为它们通常归因于血栓素而非血脂异常。然而，有人断言昔布类诱发的梗死本质上是“常规”梗死，因为血栓素的风险与多种“常规”风险因素的风险基本相同。昔布类和“常规”风险因素都被认为会引发血栓形成/血管收缩，正是这种表现使得昔布类诱发的梗死本质上成为“常规”梗死。血栓形成/血管收缩对于心肌梗死的诱发至关重要；血栓形成是公认的机制，而（阻力血管的）痉挛是一种被提出的梗死机制。还有人断言昔布类诱发的梗死存在大量“常规”风险因素，并且昔布类的风险叠加了“常规”风险因素的风险。大量“常规”风险因素与昔布类风险的组合被认为是导致昔布类诱发梗死的必要条件。要确切区分许多（即便不是大多数）罗非昔布诱发的梗死病例将很困难；这是因为难以评估“常规”风险因素相对于罗非昔布风险所带来的风险，并且将讨论区分中的具体问题。然而，合理的是，事件发生时间短的梗死往往是罗非昔布诱发的；紧跟新风险因素（如配偶离世或压力）之后发生的梗死，更倾向于自动归因于新风险因素。由此可知，事件发生时间长的梗死往往不是罗非昔布诱发的。此外，与过去的做法相反，不能因为存在大量“常规”风险因素就将梗死认定为非罗非昔布诱发的梗死；毕竟，罗非昔布诱发的梗死合理地与大量此类风险因素相关。
