The principal molecular mechanisms underlying the cardiovascular (CV) and renal adverse effects of nonsteroidal anti-inflammatory drugs (NSAIDs), such as myocardial infarction and hypertension, are understood in more detail than most side effects of drugs. Less is known, however, about differences in the CV safety profile between chemically distinct NSAIDs and their relative predisposition to complications. In review article, we discuss how heterogeneity in the pharmacokinetics and pharmacodynamics of distinct NSAIDs may be expected to affect their CV risk profile. We consider evidence afforded by studies in model systems, mechanistic clinical trials, a meta-analysis of randomized controlled trials, and two recent large clinical trials, Standard Care vs. Celecoxib Outcome Trial (SCOT) and Prospective Randomized Evaluation of Celecoxib Integrated Safety versus Ibuprofen or Naproxen (PRECISION), designed specifically to compare the CV safety of the cyclooxygenase-2-selective NSAID, celecoxib, with traditional NSAIDs. We conclude that SCOT and PRECISION have apparently not compared equipotent doses and have other limitations that bias them toward underestimation of the relative risk of celecoxib.

非甾体抗炎药（NSAID）的心血管（CV）和肾脏不良作用（如心肌梗塞和高血压）的主要分子机制比大多数药物的副作用更为详细地了解。然而，关于化学上不同的非甾体抗炎药之间的心血管安全性差异及其对并发症的相对易感性知之甚少。在综述文章中，我们讨论了不同NSAIDs的药代动力学和药效学中的异质性如何影响其CV风险谱。我们考虑了模型系统研究，机制临床试验，随机对照试验的荟萃分析以及两项近期的大型临床试验（标准护理与临床试验）提供的证据。Celecoxib结果试验（SCOT）和Celecoxib综合安全性与Ibuprofen或Naproxen的前瞻性随机评估（PRECISION），是专为比较环氧合酶2选择性NSAID，celecoxib和传统NSAID的CV安全性而设计的。我们得出的结论是，SCOT和PRECISION显然没有比较等效剂量，并且还有其他局限性，使他们倾向于低估celecoxib的相对风险。