Vascular viewpoint

Question: What are the effects of celecoxib, a selective COX-2 inhibitor on endothelial function? Population: Fourteen male patients (46-77 years) with severe coronary artery disease and chronic stable angina who did not have a coronary revascularization procedure three months prior to randomization. All patients were on aspirin and statins. Design and methods: Randomized double-blind, placebo-controlled crossover study. All patients received celecoxib 200 mg twice a day or matching placebo for two weeks. One patient discontinued study medication and was not included in the fi nal analysis. The primary outcome was endothelial function as assessed by flow-mediated and glycerol nitrate-induced vaso-dilation of the brachial artery after each treatment period using a high-resolution ultrasound device (10 MHz linear array transducer; WTS-2, Pie Medical, Indianapolis, IN, USA). Flow-mediated dilatation of the brachial artery was induced by the release of a wrist cuff inflated to suprasystolic blood pressure for 5 min. After release of the cuff pressure the arterial diameter was recorded every 15 s for 3 min. Secondary outcomes included oxidized LDL-cholesterol, high-sensitivity C-reactive protein (CRP) and prostaglandins (prostaglandin E 2 , 6-keto-prostag-landin-F 1 a -a stable metabolite of prostaglandin I 2 ) and thromboxane B 2 (an immediate and stable metabolite of thromboxane A 2 ). Heart rate and blood pressure were also assessed. Results: Flow-mediated vasodilation signifi cantly increased after celecoxib administration compared with placebo (3.3 6 0.4% versus 2.0 6 0.5%, p = 0.03). Glyceryl trinitrate (GTN)-induced vasodilatation remained unchanged. High-sensitivity CRP and oxidized LDL were signifi cantly lowered by celecoxib as compared with placebo (p = 0.02 and p = 0.03 respectively), and the prostaglandins, including thromboxane B 2 , were not signifi cantly altered. No changes in clinical parameters such as heart rate and blood pressure were observed. Conclusion: Selective COX-2 inhibition improves endothelium-dependent vasodilation, reduces low-grade chronic inflammation and oxidative LDL in patients with coronary artery disease.