Nonsteroidal Anti-Inflammatory Drugs and Cardiovascular Risk Is Prostacyclin Inhibition the Key Event?

Selectivity toward cyclooxygenase ( COX)-2 is usually defined by comparing the capacity of individual nonsteroidal anti-inflammatory drugs ( NSAIDs) to inhibit in vitro or ex vivo the generation of thromboxane A(2) (TXA(2)) through COX-1 in aggregating platelets with the capacity to inhibit prostaglandin ( PG) E-2 generation through COX-2, expressed in leukocytes after an inflammatory stimulus ( 1). This rather simple test has been regarded as the most useful tool to define a priori the gastric tolerability and potential anti-inflammatory capacity of new NSAIDs, but has turned out to be a criterion to identify potential cardiovascular damage associated with the use of selective or nonselective COX-2 inhibitors and to interpret the results of clinical trials.