A pathogenetic mechanism for COX-2 inhibitor-induced cardiovascular events proposed to be useful in structuring medical testimony in rofecoxib trials.
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.
Hellstrom
H R
HR
hellstro@twcny.rr.com
D002986:Clinical Trials as Topic / Q000379:methods*; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects*; D005104:Expert Testimony; D006706:Homeostasis / Q000187:drug effects*; D006801:Humans; D008955:Models, Cardiovascular; D009203:Myocardial Infarction / Q000139:chemically induced* / Q000503:physiopathology*; D018570:Risk Assessment / Q000379:methods; D012307:Risk Factors
D052246:Cyclooxygenase 2 Inhibitors