Introduction: The EMPA-REG OUTCOME is a cardiovascular safety study with empaglifozin that has shown a reduction in cardiovascular mortality and a decrease in hospitalization for heart failure. Our work is based on the analysis of the protocol that recognized five changes, the last, 3 years after the start of the study and which affects the definitions of the elements of the primary composite, and following these modifications, we find that the mortality Cardiovascular was increased by 67% in favor of empaglifozin, and myocardial infarction was underestimated, which leaves some doubt about the reality of cardiovascular benefit in this study.
Method: Our work is based on the analysis of the protocol that recognized 5 changes, these changes affect the definitions of the elements of the primary composite
1) Cardiovascular mortality: undetermined cause mortality is considered as a presumed cardiovascular death.
2) myocardial infarction: silent myocardial infarction is excluded from myocardial infarction.
Results: 1) cardiovascular mortality: this is the only cardiovascular safety study that has considered undetermined cause mortality to be presumed cardiovascular mortality, which has increased cardiovascular mortality by 67%, and this increase is 53% higher in the placebo arm compared with the empagliflozin arm.
2) myocardial infarction: in this study silent myocardial infarction is excluded from myocardial infarction, but the problem, we can not evaluate the impact of this change, because the results of silent myocardial infarction reported, only affects 53% of the population studied.
Conclusion: The play on words used to define cardiovascular mortality for the benefit of empagliflozin, and the retention of information about the number of the silent myocardial infarction, leave some doubt about the real cardiovascular benefit of this study, whose results have been taken into consideration to make cardiovascular safety a criterion in the therapeutic choice in the latest recommendations of ADA EASD 2018.
18 - 21 May 2019
European Society of Endocrinology