Cardiovascular Safety of Non-Steroidal Anti-Inflammatory Drugs. Lights and Shadows

Abstract

secondly, not even the protective effect of aspirin, that in clinically controlled trials was found to have a maximal reduction close to 30%, could explain the magnitude in the excess risk for MI observed in those exposed to rofecoxib in VIGOR. The withdrawal of rofecoxib in 2004 was motivated by the results of another study, APPROVe, which was not specifically designed to evaluate cardiovascular safety of the drug, but to study its hypothetical protective effect against the recurrence of intestinal polyps. 8 This study was prematurely stopped due to an excess in the atherothrombotic events in the group with rofecoxib, compared to the placebo group. Nonetheless, another clinical trial in patients with Alzheimer did not show an increase in the cardiovascular risk associated with this The cardiovascular safety profile of non-steroidal anti- inflammatory drugs (NSAID) is being questioned since the publication of the results of several clinical trials and observational studies. True, at the beginning research focused exclusively on selective inhibitors of cyclo- oxygenase 2 (COX-2, also known as coxib, but the results of some recent studies indicate that the increase in the risk of cardiovascular disease could more or less be shared with some traditional NSAID (NSAIDt). The use of NSAID has been associated with a larger risk of hipertension 1 and heart failure, 2,3 and its possible association with the development of atherothrombotic disease emerged towards the end of the nineties. In 2000 the first epidemiological study that showed a small increment in the risk of myocardial infarction (MI) associated with the chronic use of NSAIDt was published. 4 Around the same time, coxibs started to be commercialized worldwide. The unexpected rise in the cardiovascular risk observed in patients that had been treated with high doses of rofecoxib in the VIGOR 5 study, together with the results of 2 other previous pharmacologic studies on coxibs 6,7 seemed to point at a class effect regarding cardiovascular damage, as a consequence of the suppression of prostacyclin in the absence of thromboxane A 2 (TXA 2 ) inhibition. In this way, a selective inhibition of COX-2 could reduce the cardioprotective effects of prostacyclin in the vascular endothelium, whose synthesis of mediated by this enzyme, without inhibiting the proaggregation effects of TXA 2 , whose production is primarily controlled by the isoenzyme cyclo-oxygenase 1 (COX-1). Nonetheless, there where those who postulated that the observed result did not correspond to a rofecoxib-associated increment in the risk, but to a hypothetical cardioprotective effect of the drug it was being compared to, namely naproxen, because this NSAID has a long half-life and a greater affinity for COX-1 in a reversible manner, different from aspirin which irreversibly acetylates the enzyme and