I HIGHLY recommend that you all watch this 12 minute presentation on the cardiovascular outcomes of EMPA-REG OUTCOME presented by Dr. Silvio Inzucchi. Pay attention to the number of patients in each arm, the hazard ratio/relative risk reduction, the p-values and the particular outcomes presented.

Jardiance decreased cardiovascular death by 38% and decreased all cause mortality by 32%, but because Jardiance essentially had a neutral effect on non-fatal heart attack and non-fatal stroke the overall RRR for the 3-point MACE (death, non-fatal heart attack, non-fatal stroke) was only 14%. And this 14% RRR barely met statistical significance (p=0.0382 with p=0.0498 being their threshhold for significance). This was with ~2300 placebo patients and ~4600 Jardiance treated patients with an average treatment period of 36 months. The ~4600 treated patients were half 10 mg dose and half 25 mg dose. If they only looked at 3-point MACE RRR for the 10 mg or the 25 mg group, they only achieved p=0.0668 and p=0.0865, respectively. Furthermore, if they added unstable angina, which also had a neutral effect of Jardiance treatment, to give a 4-point MACE metric, they no longer achieved significant RRR for the ~4600 treated vs. ~2300 placebo.

In terms of % of patients that experienced a MACE over time, it looks like about 2% of the placebo patients experienced a 3 point MACE event every 6 months. So at 6 months 2% of the patients had experience an event, at 12 months 4% at 24 months 8%, at 36 months 12% and at 48 months 16%.

My biggest question for Resverlogix is how will they structure the BETonMACE primary outcomes/endpoints to allow BETonMACE to not be solely dependent on the combined 3-point MACE metric to determine success/failure of the trial but instead allow just cardiovascular death, for example, to be the metric of success if appropriate.

BearDownAZ