There are many theories about why selective inhibitors of the second isoform of cyclooxygenase (COX-2) increase cardiovascular risk. Although torcetrapib raises blood pressure and cardiovascular risk, it has been difficult to prove such a link for COX-2 inhibitors in randomized clinical trials. This review shows a significant correlation in placebo-controlled trials between the five agents' elevations in blood pressures and their rate ratios for cardiovascular events. A larger body of evidence arises from randomized clinical trial comparisons of selective versus nonselective inhibitors of COX-2, but these results are heterogeneous for naproxen versus other traditional agents. The best current trial evidence comes from the centrally adjudicated placebo-controlled trials of celecoxib for colonic polyps: If the blood pressure did not rise at 1 or 3 years after randomization, cardiovascular risk did not significantly increase. Many more data will become available in 2013, after the only prospective clinical trial involving cardiovascular end points is completed
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