Great post Pomp.

Koo, you wrote in an earlier post "In past cvot trials, as the trials progressed to thd end i would imagine even the placebo MACE rates declined. Do you know what were the lowest Placebo MACE rates seen in trials similar to our BETonMACE trial,...?"

Pomp addresses much of this in an earlier post. EXAMINE and ELIXA are really the only trials with similar patient populations. EXAMINE was diabetics with ACS event w/i 90 days. ELIXA was diabetics with ACS event w/i 180 days. As Pomp wrote, the time to randomization following ACS event was at roughly 52 days (paper indicates mean 45 days) and 75 days (paper indicates median 72 days), respectively, for EXAMINE and ELIXA respectively. BETonMACE time to randomization following ACS event is median 34 days. 

For ELIXA,  placebo event rate was ~13% at median follow up of 25 months, which equates to ~6.4 events per 100 patient years. However, this was 4-point MACE including unstable angina, which only comprised about 2.5% of total 4-point MACE events. So 97.5% of total events were 3-point MACE events.

For EXAMINE, placebo event rate was ~12% at median follow up 1.46 years. This is for 3-point MACE. They don't state an events per 100 patient year value, but I estimate about ~8.1 events per 100 patient years.

This doesn't exactly address Koo's question of declining placebo event rate over time. However, one can look at the Kaplan-Meier curves to see the decline over time.

BearDownAZ