Howard Patricia A, Delafontaine Patrice
Department of Pharmacy Practice, University of Kansas Medical Center, Kansas City, Kansas 66160-7231, USA.
J Am Coll Cardiol. 2004 Feb 18;43(4):519-25. doi: 10.1016/j.jacc.2003.09.043.
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.
非甾体抗炎药（NSAID）抑制环氧化酶（COX），该酶至少以两种同工型存在，即COX-1和COX-2。阿司匹林及该类中的老药是COX-1和COX-2的非选择性抑制剂。被称为“昔布类”的新药是COX-2的选择性抑制剂。在非甾体抗炎药中，只有阿司匹林已被证明能显著降低心血管风险，主要是通过抑制COX-1介导的血小板聚集。有人提出，其他非选择性药物，尤其是萘普生，可能提供一定程度较低的心脏保护作用，但缺乏确凿证据。相反，有人担心COX-2抑制剂可能会增加心血管风险。然而，这种潜在的不良心血管效应的机制尚不清楚，而且我们对COX-2在心血管功能中的作用的理解越来越不完整这一点也日益明显。一些研究表明COX-2对心血管功能有潜在的有益作用，而这种作用可能会被COX-2抑制所抵消，而其他研究则报告使用COX-2抑制剂可改善内皮功能。此外，阿司匹林与其他COX抑制剂联合治疗的影响尚不清楚。本文将综述研究这些问题的相关研究。
