Re: DECLARE TIMI-58 w/ prior MI as BETonMACE proxy?
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posted on
Mar 29, 2019 02:37PM
Cabel asked "Can you remind us again what the EXAMINE placebo rate per 100 patient years was again,...? around 12%,..?" and Lost_Soul responded "Examine trial placebo event rate ~ 11.8%"
The 11.8% is the placebo event rate at the median dosing period of 18 months, not the events per 100 patient years. This EXAMINE study didn't report in events per 100 patient years; however, I think one can just divide 11.8% by 1.5 years to get 7.87 events per 100 patient years.
Topcoin wrote "One takeaway of Declare data is that this SGLT2 reduced 3 Point Mace events by 2.6 %. BOM shows only 11% of patients are on this class of medications as a SOC addition. So I believe this translates into only a 0.25% reduction in 3 Point Mace in total and placebo BOM population; this may be evidence that Examine indeed may be a very solid model of BOM placebo event rates ? And not skewed very much at all by improved/ newer SOC SGLT2 medications ?"
Just to clarify, the 2.6% was the reduction in absolute risk, not the relative risk reduction, in the sub-study of DECLARE TIMI-58 looking at patients with prior MI (median time from MI was 5.4 years). The 3-point MACE risk reduction of SGLT2 inhibitors in a patient population more similar to BETonMACE is likely much greater, since these folks experienced their most recent event within a median of ~34 days. Dapagliflozin wasn't the first to report CVOT in this SGLT2 inhibitor class. The EMPA-REG OUTCOMES and CANVAS trials for empagliflozin and canagliflozin, respectively, reported earlier and both achieved significant 14% RRR in 3-point MACE in the total population vs. a non-significant 7% RRR for dapagliflozin in the total population for DECLARE TIMI-58. Your point about only 11% of BETonMACE patients being on a SGLT2 inhibitor at baseline is well taken. However, we don't know which SGLT2 inhibitor these folks are on and some SGLT2 inhibitors may have better MACE reduction than others.
Topcoin also wrote "Ditto for published GLP effect data; only 11% of BOM population, so again minimal skew ?"
Actually, according to the recent ACC poster only 0.4% of the BETonMACE folks are on a GLP1-R agonist. Different GLP1-R agonists have elicited different MACE reduction results in CVOTs. For example, Lixisenatide in ELIXA, which had a diabetic population with ACS within 180 days, elicited no reduction in 3-point MACE. However, other GLP1-R agonists in lower risk diabetic poplulations have achieve reductions in 3-point MACE ranging from 9% to 26%. Perhaps your incorrect 11% number was for those on a DPP4 inhibitor. No worry there.....no DPP4 inhibitor has shown 3-point MACE reduction in a CVOT yet.
BearDownAZ