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 r ole in the maintenance of cardiovascular hemostasis. Thromboxane A(2) (TxA( 2)), 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 I-2 (PGI(2)), which appears to be synthesized by COX-2, coun teracts most of these effects of TxA(2). 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 sug gest no overall effect of traditional NSAIDs on the risk of CHD. No specifi c dose or duration response was found. The lack of cardiovascular protectio n associated with non-specific NSAIDs observed in these four studies leaves little room for an important cardioprotective class effect. In light of th ese findings, the potential minor cardiovascular effects of specific COX-2 inhibitors need to be evaluated in large populations.