The effect of NSAIDs on the risk of coronary heart disease: fusion of clinical pharmacology and pharmacoepidemiologic data.
The isozymes cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) catalyze the conversion of arachidonic acid to eicosanoids that play an important role in the maintenance of cardiovascular hemostasis. Thromboxane A2 (TxA2), which is primarily synthesized by platelet COX-1, causes irreversible platelet aggregation, vasoconstriction and smooth muscle proliferation, all of which are linked to coronary heart disease (CHD). In contrast, vascular prostaglandin I2 (PGI2), which appears to be synthesized by COX-2, counteracts most of these effects of TxA2. Inhibition of the COX isozymes by nonsteroidal anti-inflammatory drugs (NSAIDs) or COX-2 selective inhibitors may therefore influence hemostasis and the risk of CHD. Four epidemiologic studies with differing study designs and populations suggest no overall effect of traditional NSAIDs on the risk of CHD. No specific dose or duration response was found. The lack of cardiovascular protection associated with non-specific NSAIDs observed in these four studies leaves little room for an important cardioprotective class effect. In light of these findings, the potential minor cardiovascular effects of specific COX-2 inhibitors need to be evaluated in large populations.
García Rodríguez
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LA
Centro Español de Investigación Farmacoepidemiológica (CEIFE), Madrid, Spain. lagarcia@ceife.es
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D003327:Coronary Disease / Q000453:epidemiology* / Q000378:metabolism / Q000517:prevention & control; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000378:metabolism; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins; D009203:Myocardial Infarction / Q000453:epidemiology / Q000517:prevention & control; D017891:Pharmacoepidemiology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D012307:Risk Factors; D013928:Thromboxane A2 / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D013928:Thromboxane A2; D011464:Epoprostenol; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases