INTERVIEW
Crushing It in the Setting
of PCI for STEMI
Crushed prasugrel speeds antiplatelet effects
We know that time is muscle. The effects of
platelet inhibitory induced by oral P2Y12 receptor
antagonists can be delayed in patients with STEMI
undergoing PCI, which may be related to reduced
absorption. CardioSource WorldNews: Interventions
spoke with Dominick Angiolillo, MD, PhD, Professor of Medicine and Director of
Cardiovascular Research at the University of Florida College of Medicine
in Jacksonville, FL, about the Crush
Study, which examined if crushing
Dominick Angiolillo, prasugrel could lead to more favorMD, PhD
able results.
CSWN Interventions: What triggered the
Crush Study?
There were several ideas that led to the design of
the study. We’ve learned, over the course of the
past several years, conducting a series of pharmacod ynamic studies, that, although the newer
P2Y12 inhibitors act more promptly, in the vast
majority of patients, it doesn’t seem to be the case
in patients with ST-segment elevation myocardial infarction (STEMI). There is a time delay in
the onset of the effects. We also know that time
is muscle, and therefore efforts to accelerate the
effects of the drugs are clearly needed. Along this
pathway of investigations, there was one seminal
study by our colleagues in Italy and Greece called
the MOJITO study (Mashed Or Just Integral pill of
TicagrelOr), which actually crushed the tablets, in
that specific case, ticagrelor. The study did show
that there was an enhanced platelet inhibitory
effect at 2 hours after giving the drug compared
with the whole tablets.
We wanted to expand these findings. The Crush
Study expands in three ways. First, we looked at
a different drug—in this case prasugrel. Secondly,
we conducted a more comprehensive pharmacodynamic study by adding more time points and
more pharmacodynamics assays, just to provide
confirmatory results. Finally, we wanted to have
some mechanistic insights; to do so, we looked
at pharmacokinetic assessments to really understand if this was attributed to a differences in drug
absorption and metabolism.
30 CardioSource WorldNews: Interventions
So what did you find?
We randomized and analyzed 52 patients, so a
relatively small study, but a very detailed physiologically based pharmacokinetic (PBPK) study.
These patients were randomized in a one-to-one
fashion to either crushing the pills or taking the
standard whole tablets of 60 milligrams of prasugrel; in other words, six ten-milligram pills. We did
a series of assessments at 7 time points using two
different pharmacodynamic assays and pharmacokinetic assessments. It was a lot of work, a lot of
in the first 24 hours, it’s still pretty significant for many places.” And so anything you
can do to speed up the process and protect
these patients has to be a good thing.
Absolutely. And crushing is a way; it’s really
simple. You know, there are also some other comments from others that I’ve heard: “It’s complicated to crush the tablets.” We used a syringe crusher,
and the approximate time to prepare the crushed
sample was around 2, max 3 minutes. So it’s very,
very simple. With the syringe crusher, you put
We found that there were differences in the
pharmacodynamic effects already at 30 minutes
versus, say, at 1 hour, 2 hours, and 4 hours. It was
only after 6 hours that the two curves, or the two
treatment arms, actually emerged.
sleepless nights to conduct these assessments. We
found that there were differences in the pharmacodynamic effects already at 30 minutes versus, say,
at 1 hour, 2 hours, and 4 hours. It was only after
6 hours that the two curves, or the two treatment
arms actually emerged.
in the six tablets. You crush them. It turns into
a powder in a matter of a couple of twists. Take
some water. Shake it. Put it in a cup. Take some
residue. Take some more water to rinse it. Put it in
a cup. Drink. And it’s done. ■
REFERENCE:
For the MOJITO study, the accelerated
effects were a little slower, right?
They did not find it quite at 30 minutes. It was
not as quick—1 hour. But it did show a difference.
But out of fairness, it is important to say that they
were different studies, with different drugs, with
also some different type of assessments and timing of administration, etc. So we were very encouraged because we found a quick and cheap way to
accelerate platelet inhibition because essentially
you’re taking the same exact drug at the exact
dose and just giving it a different formulation.
In the editorial comment to your paper, the
writers say, “At the rate of stent thrombosis,
Rollini F, Franchi F, Hu J, et al. J Am Coll Cardiol.
2016;67(17):1994-2004.
To watch the full interview with
Dominick Angiolillo, MD, PhD, visit
the CSWN YouTube channel or scan the
QR code. Interview conducted by Rick
McGuire.
Editor’s note: This interview was edited from transcript.
July/August 2016