Can we go beyond surrogates?
Abstract
Two years ago, data presented at the annual American Diabetes Association (ADA) meeting in New Orleans showed a marked decrease in deaths, especially those due to cardiovascular disease, with the use of empagliflozin. Two major questions have been asked: (i) was the result a fluke; and (ii) was it a class effect, or was it specific to the agent used? The hope that both questions would be answered by a second study has been answered: the conclusions of EMPA-REG were not an anomaly and it is a class effect, not one caused by a specific drug. Importantly, do these studies require us to alter our algorithms for the treatment of type 2 diabetes? The CANagliflozin cardioVascular Assessment Study (CANVAS) was designed similarly to EMPA-REG, enrolling individuals who either had known cardiac disease or were at high risk for cardiac disease. In fact, CANVAS involved two stages, CANVAS and CANVAS R, which can be analyzed together. There were 10 142 patients in the combined trial followed for a mean of 3.6 years. The average age was 63.3 years, 35.8% were women, the mean duration of diabetes was 13.5 years, and 65.6% had known cardiovascular disease. In EMPA-REG, 7020 patients were followed for 3.1 years, 28.5% were women, and all had established cardiovascular disease. The primary endpoint of both studies was the composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. In both studies, the components of the composite endpoint were studied along with…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 7,020 participants or records.
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