The VIGOR and APPROVe trials led to rofecoxib withdrawal due to the high risk of thrombotic events, which was supported by a meta-analysis of 28 RA studies published by Roubille et al. This study reported an 18% increased risk of all CV events (RR, 1.18; 95% CI 1.01 to 1.38; p = 0.04) and strokes with a greater effect with COX-2 inhibitors (RR, 1.36; 95% CI 1.10 to 1.67; p = 0.004) than with nonselective NSAIDs (RR, 1.08; 95% CI 0.94 to 1.24; p = 0.28) [88,91]. This evidence concerns the gene PTGS2 and rheumatoid arthritis.