INTERVIEW
Effects of High Dose
Rosuvastatin in Nonintervened Vessels
An interview with Hector Garcia, MD, PhD
high dose rosuvastatin loading before percutaneous coronary intervention (PCI) reduces the
myocardial damage and the incidence of adverse
cardiac events in patients with stable angina and
acute coronary syndrome. However, recently, no
studies were present focusing on rosuvastatin
loading in patients with ST-segment
elevation myocardial infarction
(STEMI) in a primary PCI setting
until the Integrated Biomarker and
Imaging Study (IBIS). CardioSource
Hector Garcia, MD WorldNews: Interventions spoke with
Hector Garcia, MD, PhD, about the
final results of IBIS-3 on the use of rosuvastatin in
non-intervened vessel of a real-practice population.
CSWN: Interventions: Tell us about the IBIS3 trial and what you found.
Hector Garcia, MD, PhD: The IBIS-3 study
was a single-center, 300-patient study aiming at
imaging the patients at index, and then repeating
the imaging at 12 months. We wanted to test the
effects of rosuvastatin in the coronary artery of
those patients by means of using intravascular
ultrasound, mainly, but, also, particularly, with
the use of the radiofrequency analysis, which is
commercially called virtual histology, and with
the TVC NIRS catheter. We imaged one of the
non-culprit or non-target vessels in this population, a segment a bit longer than 48 millimeters.
We had a study population with a very broad
spectrum of coronary aortic disease. We included
patients from stable angina, unstable angina,
non-STEMI and STEMI populations.
Our primary endpoint was the change in the
necrotic core, as evaluated by radiofrequency
IBIS analysis. For that particular endpoint, we
found no significant change from baseline to
follow-up, when considering the necrotic core volume as the primary endpoint. And, similarly, for
another key secondary endpoint, which was the
change in LCBI, an index measuring the amount
of lipid in the coronary arteries, using this TVC
catheter, we also did not observe any significant
change in the segments with this catheter over
the 12-month period.
30 CardioSource WorldNews: Interventions
So we could conclude two things: On one
hand, rosuvastatin did not change the signal coming out of these two different imaging modalities,
which is very hard to accept, but that could be a
real observation. Or, on the other hand, the other
endpoint that we have elected for this study was
perhaps not the best for evaluating the facts of
rosuvastatin. So there are two angles.
But the time of follow-up may be a factor, as
we have only a traditional 12-month follow-up.
Perhaps we were reimaging those patients too
shortly after the intervention, and we could have
maybe waited another year to see an effect.
Tell us about IBIS-4, the substudy of the
COMFORTABLE AMI trial of individuals who
underwent stenting for ST-segment elevation. What did this analysis of the “virtual
histology” on the non-target lesion vessels
show?
IBIS-4 was another multi-modality imaging study
but, in this case, a multi-center study of STEMI
patients, treating the culprit artery. We imaged
the newly stented vessel, as well as the other two
vessels in the same patient. So the full coronary
tree was imaged at baseline with two different
imaging modalities—virtual histology and optical
coherence tomography (OCT).
We gave study patients 40 mg of rosuvastatin
for a period of 13 months, and we will repeat
that in the three coronary vessel of those patients, using OCT and virtual histology. So the
observations from that study—with necrotic core
being the primary endpoint—for the radiofrequency analysis, we did not observe any change,
similarly to the IBIS-3 findings, in this post-STEMI population; however, our OCT findings were
of interest.
For OCT, we wanted to measure the change
in the thickness of the fibrous cap. Because the
resolution of the imaging modality is about 1015 microns, we were able to capture the small
changes occurring over time in the fibrous cap.
We observed a thickening in the fibrous cap, suggesting less-vulnerable spots. We also observed a
reduction in the lipid pool as measured by OCT.
And maybe a unique finding is the fact that we
measured the accumulation of macrophages at
index and then repeated that OCT analysis at the
follow-up, and we observed a reduction in the accumulation of macrophages in the vessel wall of
those patients.
So you could say, so far, considering IBIS-3
and IBIS-4 together, with 1-year treatment with
rosuvastatin, we did not change the amount of
necrotic core present in those vessels but, when
we use the OCT—perhaps because of the resolution of the imaging modality—we observe significant changes in the thickness of the fibrous cap,
reduction in the lipid pool, and also a reduction
in the macrophage accumulation.
So do you think there is still a benefit to better understanding vulnerable plaque?
When we see these dramatic reductions in cardiovascular events after starting treatment with
statins, we need some explanation as to why that
is happening. One way to do that is by imaging
the actual plaques that are being treated. But
that’s not the only way—we have other tools like
biomarker and genetic assessments. Assessing
changes in all those areas would impact or explain the reductions in cardiovascular outcomes
in these statin trials. We are just coming with one
piece of the puzzle and trying to contribute to
that whole discussion to better understand how
we are impacting the cardiovascular outcomes of
our patients.
But we aren’t just focusing on the vulnerable
plaque, the focal changes in the vessel wall that
may not have any clinical
impact—we are also foTo watch the
interview with
cusing on the vulnerable
Hector Garcia, MD,
patient. ■
PhD, visit the CSWN
YouTube channel or
scan the QR code.
Editor’s note: This interview
was edited from transcript.
May/June 2016