P2Y12 Inhbitors in the ED for NonSTEMI. Criticisms of the ACCOAST-ed trial of Upstream vs. Delayed Prasugrel

Rick Body had a nice piece in St. Emlyn's about the ACCOAST-ed trial, a study recently published in the NEJM on the use of Prasugrel in NonSTEMI: should it be given "upstream" in the ED, or should it be delayed until the anatomy is defined by angiography?  The study found no difference between upstream and waiting.

Here is Rick's piece.

I have these criticisms of the trial, and am still using Clopidogrel 600 mg for NonSTEMI:

1. Patients planned for intervention within 2-48 hours, but they do not break down the data on whether their was efficacy for those whose intervention was closer to 48 hours.  Sitting on these patients for a long time may be bad, but this study does not tell us.
2. One of the major benefits of the P2Y12 inhibitor is it would theoretically prevent further platelet aggregation during the waiting time for PCI.  The longer the time to PCI, the more likely it is to have a beneficial effect. 
3. Mean time from symptom onset to admin of Prasugrel was 15 hours in both groups.  Strange.  Patients should be receiving their P2Y12 treatment very shortly after arrival and immediately upon diagnosis of NonSTEMI.  These medicines take time to work.   Something is amiss here.
4. First loading dose to start of angiography was 4.4 hours.  So they waited a long time to give the medicine, then did angiography immediately.  Of course there is no difference if "upstream"  and "at the time of angiography" only have a 4 hour difference.
5. GRACE score > 140 vs. < 140 (the level at which Mehta et al. (NEJM 360:2165; 2009) found benefit for immediate angiography vs. delayed): they did not analyze and compare these groups even though they collected GRACE scores on all patients.  Why not?
6. The bleeding was significantly greater in the Prasugrel group, but this was only statistically, not clinically significant: rates were about 1%!!
7. Heparin is much less evidence-based than P2Y12 inhibitors.  There is ZERO evidence for its efficacy in the PCI era.  All weak evidence in its favor comes in the era of no intervention at all!