For example, the US Food and Drug Administration requested a boxed warning concerning the cardiovascular risk of NSAIDs in 2005; this warning was strengthened in 2015 to highlight that all non-aspirin NSAIDs (both COX-2 selective and non-selective) can increase the risk of heart attack and stroke (US Food and Drug Administration, 2018). This evidence concerns the gene PTGS2 and myocardial infarction.