Degree of Cyclooxygenase-2 Inhibition Modulates Blood Pressure Response to Celecoxib and Naproxen

Katherine N. Theken, Soumita Ghosh, Carsten Skarke, Susanne Fries, Nicholas F. Lahens, Dimitra Sarantopoulou, Gregory R. Grant, Garret A. FitzGerald, Tilo Grosser
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Abstract

Background Non-steroidal anti-inflammatory drugs (NSAIDs) increase the risk of adverse cardiovascular events via suppression of cyclooxygenase (COX)-2-derived prostacyclin (PGI2) formation in heart, vasculature, and kidney. The Prospective Randomized Evaluation of Celecoxib Integrated Safety versus Ibuprofen Or Naproxen (PRECISION) trial and other large clinical studies compared the cardiovascular risk of traditional NSAIDs (i.e. naproxen), which inhibit both COX isozymes, with NSAIDs selective for COX-2 (i.e. celecoxib). However, whether pharmacologically equipotent doses were used - that is, whether a similar degree of COX-2 inhibition was achieved - was not considered. We compared drug target inhibition and blood pressure response to celecoxib at the dose used by most patients in PRECISION with the lowest recommended naproxen dose for osteoarthritis, which is lower than the dose used in PRECISION.
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环氧化酶-2 的抑制程度可调节血压对塞来昔布和萘普生的反应
背景 非甾体抗炎药(NSAIDs)通过抑制心脏、血管和肾脏中环氧化酶(COX)-2 衍生的前列环素(PGI2)的形成,增加心血管不良事件的风险。塞来昔布综合安全性与布洛芬或萘普生的前瞻性随机评估(PRECISION)试验和其他大型临床研究比较了同时抑制两种 COX 同工酶的传统非甾体抗炎药(如萘普生)和选择性抑制 COX-2 的非甾体抗炎药(如塞来昔布)的心血管风险。不过,我们并未考虑是否使用了药理等效剂量,即是否达到了类似的 COX-2 抑制程度。我们比较了PRECISION中大多数患者使用的塞来昔布剂量与治疗骨关节炎的萘普生最低推荐剂量(低于PRECISION中使用的剂量)的药物靶点抑制作用和血压反应。
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