INTERVIEW
A COGENT Argument
for More Use of PPIs
with DAPT
Low-dose aspirin is as effective as high-dose aspirin in secondary cardiovascular prevention, and
yet some doctors continue to prescribe high-dose
aspirin in the setting of dual antiplatelet therapy.
Taking a deeper look at the COGENT study results, a recently published paper in JACC reported
that proton-pump inhibitors were associated with
reduced gastrointestinal events regardless of
aspirin dose in patients requiring dual antiplatelet
therapy. In this interview, CSWN Executive Editor Rick McGuire spoke with one of the study’s
authors, Deepak Bhatt, MD, who is the executive
director of interventional cardiovascular programs at Brigham and Women’s Hospital and a
professor at Harvard Medical School. This interview was conducted at ACC.16 in Chicago.
CSWN: Why are people still using high-dose
aspirin in DAPT?
Dr. Deepak Bhatt: So as it turns out, if you look
at registry data, even the most contemporary registry data for chronic maintenance aspirin dosing,
there’s still a fair amount of doctors that are recommending or patients that are taking high-dose
aspirin, that is 324 or 325 mg a day. I’m not sure
why because the guidelines no longer endorse
that approach.
There’s no clearer cut benefit of higher-dose aspirin in terms of antiplatelet or anti-thrombotic efficacy, and there’s some evidence that it might raise
the risk of gastrointestinal bleeding. In fact, the current trial showed that in a randomized fashion, but
it’s a U.S. thing. That is, outside the U.S., in general,
people are using low-dose aspirin for maintenance
therapy for cardiovascular indications, but in the
U.S. for some reason, use of that higher dosing of
aspirin for maintenance therapy persists.
Now, what was the genesis for the paper
that’s being publish ed in the April 12th issue
of JACC on PPIs?
Sure. Yeah, so this is from the COGENT trial. The
initial results were published in the New England Journal of Medicine a couple years ago. That
study showed, for the first time, that prophylactic
proton-pump inhibitor versus placebo reduced
clinical gastrointestinal bleeding in patients on
dual antiplatelet therapy who weren’t believed to
be at particularly high risk of GI bleeding other
38 CardioSource WorldNews
than that they were on DAPT,
but these weren’t GI bleeders—or other populations
where proton-pump inhibitors
previously had been shown
to reduce GI bleeding. So that
was the COGENT trial.
This new analysis from
the trial looks specifically at
patients on high-dose aspirin at
baseline and those on low-dose
aspirin at baseline and found a
benefit of PPIs in reducing gastrointestinal bleeding in both
those subgroups. The reason we
did it was there was a though, actually, that in the
low-dose aspirin, maybe the GI bleeding rates would
be so low that you didn’t need the proton-pump inhibitor, but as it turned out, the proton-pump inhibitor was a benefit in both those different subgroups.
So is it worth adding this particular agent for
any patient who’s on aspirin with DAPT?
That’s a great question. To be clear, the guidelines
and expert consensus documents in the U.S. and Europe do not support that very liberal approach, with
PPI for everybody on dual antiplatelet therapy. They
support selective use—that is, in patients at high
bleeding risks such as those with previous GI bleeding, maybe those with H-pylori (although you’d want
to treat that), patients that are on chronic nonsteroidal anti-inflammatory drugs or on chronic oral steroids. Those drugs can raise GI bleeding risk, maybe
very elderly patients, certainly patients on triple
antithrombotic therapy. That is an anticoagulant in
addition to DAPT. All those patients, the guidelines
and expert consensus documents say should definitely be on a prophylactic proton-pump inhibitor,
but patients who are a lower risk than that, there’s
no formal recommendation to do that, although our
study actually did include patients like that, not in
that former group. It was actually a low GI bleeding
risk population, and we still found benefit.
As the editorial comment to your paper
notes, there has been a lack of enthusiasm
for the use of PPIs in patients on low-dose
aspirin. Does that need to change?
I think for patients that are at high GI bleeding
risk, yes. Now, I don’t want to be too cavalier about
proton-pump inhibitors, because in the COGENT
study, the company that made the particular PPI
went bankrupt, so the trial ran a 6-month duration,
but not longer. It was intended to go longer, so
we can say from a cardiovascular perspective that
the proton-pump inhibitor was safe, no pinnacle
interactions or anything out to 6 months, and if
there was going to be an interaction, you’d expect
to be in that first 6 months after ACS or PCI. So
I think it’s reasonably solid for the cardiovascular
safety. Regarding the GI bleeding being reduced,
I think that’s quite solid and consistent with prior
observational theories. What we can’t comment
on from COGENT is what the risks might be of
proton-pump inhibitors continued very long-term.
I don’t mean cardiac risks, obviously not GI risk.
They’re reducing GI risk, but there have been some
concerns and reports of C. difficile diarrhea, of
increases in pneumonia, increases in fractures, and
so on. It’s difficult to know if any of these things are
real because that’s based largely on observational
data. If you’re looking at older patients on PPIs,
of course they have more fractures, but maybe
that’s because they’re older. We actually need more
randomized data to make sure that long-term PPI
use doesn’t have some of these other off-target,
non-cardiac, non-GI, bad side effects. That’s why I
wouldn’t be too cavalier about just saying “PPIs for
everybody forever,” but for sure when patients are
at high risk of bleeding, including those on DAPT,
and especially during a period of intense treatment,
I think it’s worth weighing their GI bleeding risk
and considering a proton-pump inhibitor. ■
May 2016