Nonsteroidal Anti-Inflammatory drugs and cardiovascular risk

Abstract

Nonsteroidal anti-inflammatory drugs (NSAID) inhibit cyclooxygenase (COX) enzymes, which exist in at least two isoforms, COX-1 and COX-2. Aspirin and older agents in this class are nonselective inhibitors of both COX-1 and COX-2. Newer agents termed "coxibs" are selective inhibitors of COX-2. Among the NSAID, only aspirin has been proven to significantly reduce cardiovascular risk, primarily through inhibition of COX-1-mediated platelet aggregation. It has been suggested that other nonselective agents, especially naproxen, may provide some lesser degree of cardioprotection, but conclusive evidence is lacking. Conversely, there are concerns that the COX-2 inhibitors may increase cardiovascular risk. However, mechanisms for this potentially adverse cardiovascular effect are unknown, and it is becoming increasingly clear that our understanding of the role of COX-2 in cardiovascular function is incomplete. Some studies have demonstrated a potentially beneficial effect of COX-2 on cardiovascular function that could be negated by COX-2 inhibition, while other studies have reported improved endothelial function with COX-2 inhibitors. Additionally, the impact of combined therapy with aspirin and other COX inhibitors is not yet clear. This article will review the studies that have examined these issues.

Anti-inflamatórios não esteroides: Efeitos cardiovasculares, cérebro-vasculares e renais

“…In 1991, the existence of two isoforms of the cyclooxygenase enzyme were demonstrated; they were called COX-1 and COX-2 and were found to be codified by different genes, with similar chemical structures, 60% of homology in the amino acid sequence and singular patterns of expression [1][2][3] . The COX-1 isoform is expressed in a constitutive (constant) way in most tissues, whereas COX-2 is induced in inflammations.…”

Evaluation of the changes on hemostatic parameters induced by valdecoxib in male Wistar rats

“…The current hypothesis is that while selective COX-2 inhibition does not affect the proaggregatory and vasoconstricting effect of thromboxane A2 (TXA2) produced by thrombocytes, it may significantly block the COX-2 dependent production of endothelial prostacyclin (PGI2) resulting in an imbalance of the aggregatory system in fa-vor of thrombus formation and vasoconstriction. [4][5][6][7] This balance of TXA2/PGI2 is crucial to maintain hemostasis of coagulation pathways that can be evaluated by the clinical laboratory assays.…”

Repression of β-catenin function in malignant cells by nonsteroidal antiinflammatory drugs

“…The development of the more specific COX-2 inhibitors was an effort to overcome this problem. Unfortunately, these drugs may increase the risk of cardiovascular diseases (10)(11)(12)(13)(14). Accordingly, there is a major therapeutic need for agents that retain the chemopreventive actions of NSAIDs, but that are devoid of their potential toxicities.…”