Negative Trials
(Maybe Some Positive Spin)
With investigators (and those sponsoring their
trials) just wanting to get their data out ASAP,
it’s probably not surprising that we’re seeing
some major meetings with an abundance of
negative trials. Here are some from ESC.16.
TABLE 2
1-Year Target Lesion Revascularization and Target Lesion Failure Rates
Culotte Stenting
TAP Stenting
p Value
21 ± 20%
27 ± 25%
0.038
9-month binary restenosis rate*
6.5%
17%
0.006
1-year target-lesion revascularization
6.0%
12.0%
0.069
1-year target lesion failure
6.7%
12.0%
0.11
Maximum % diameter stenosis post-procedure
* Primary endpoint.
PRAGUE-18
Prasugrel vs. Ticagrelor in Patients with AMI Treated
with Primary PCI: This head-to-head comparison of
prasugrel and ticagrelor was prematurely terminated
for futility. There was no evidence that one is more
effective or safer than the other in preventing ischemic and bleeding events in this setting. Granted,
this was in a small number of patients and events.
REM-HF and MORE-CARE
Supporters of remote monitoring (REM) may not
be ‘losing their religion’ quite yet, but their faith is
being tested. Findings from the Remote Management of Heart Failure Using Implantable Electronic
Devices trial showed that REM was not associated
with reduced mortality or fewer cardiovascular
hospitalizations compared to usual care. For REM,
‘It’s not the end of the world as we know it,’ but
the MOnitoring Resynchronization dEvices and
CARdiac patiEnts trial showed no benefit on hard
clinical endpoints after recruiting just over 900
HF patients implanted with a CRT-defibrillator w ith
wireless transmission capabilities. One bonus: the
investigators reported cost savings due to a 41%
reduction of in-office visits. – JAMA (REM-HF) and
European Journal of Heart Failure (MORE-CARE)
CHART-1
The Congestive Heart Failure Cardiopoietic Regenerative Therapytrial evaluated bone-marrow stem
cells to promote heart repair, but this approach did
not significantly improve the primary outcome over
a sham procedure among patients with congestive
HF. However, it revealed what the investigators
called critical new insights, identifying a “well-defined” subgroup of patients who may benefit from
cardiopoietic cell therapy: those with severe heart
enlargement at baseline (left ventricular end-diastolic volumes between 200 and 370 ml).
ANTARCTIC
Yet another chill in the wind for platelet function
testing. The trial acronym stands for Assessment
of a Normal versus Tailored dose of prasugrel after
stenting in patients Aged > 75 years to Reduce the
Composite of bleeding, stent Thrombosis and Ischemic Complications. This time they used prasugrel,
which has a more predictable effect than clopidogrel (used in initial studies) and concentrated on
elderly patients after stenting for ACS. In short: no
clinical benefit. Senior investigator Gilles Montalescot, MD, PhD, from Hôpital Pitié-Salpêtrière (Paris,
France), said: “Platelet function testing is still being
used in many centers and international guidelines
still recommend platelet function testing in high-risk
situations. Our study does not support this practice
or these recommendations.” – Lancet
30 CardioSource WorldNews: Interventions
guided PCI or to fluoroscopy-guided PCI. The trial
was conducted at 9 hospitals in France.
Most of the benefit of OCT seemed to be in the
form of more information on top of that obtained
by angiography, leading to a change in procedural
strategy in 50% of cases. Post-procedure fractional
flow reserve, the primary endpoint, was significantly higher in those who had OCT (0.94 versus
0.92 for angiography alone; p = 0.005). In the study
arm, 82.5% of patients had a post-PCI FFR > 0.90,
compared to 64.2% in the control arm (p = 0.0001).
OCT was performed after the initial angiography
and repeated after stent implantation. The operators were encouraged to adjust their procedural
strategy according to the data immediately available
on the OCT images. The addition of pre-PCI OCT
imaging did not appear to change the procedural
strategy compared to angiography alone, but the
first OCT run performed immediately after stent
implantation showed stent malapposition in 32% of
patients and stent underexpansion in 42%. Poststent overdilation was performed in all patients
with stent underexpansion, and in 22 out of 38 of
those (58%) with stent malapposition (of whom 20
also had stent underexpansion).
The trial discussant, Stephen Windecker, MD,
of Bern University Hospital in Switzerland, noted
that OCT is recognized as a diagnostic modality in
select patients to optimize stent implantation in the
current ESC guidelines, but the recommendation
class (IIb) and level of evidence (C) reflect the lack
of randomized trial evidence guiding current clinical
practice.
Whether the “modest” improvement seen in
postprocedural FFR will translate into improved
long-term clinical outcomes and whether the
procedure is cost effective will need to be tested
in future trials, said Dr. Windecker, but there are
already some data indicating an inverse relationship between post-PCI FFR and the occurrence of
MACE. Also to be determined: whether the findings
can be extrapolated to other clinical settings, such
as ST-segment MI populations. – Circulation
CE-MARC 2: Cardiac MR reduces unnecessary angiography
What’s better than guideline-directed care? In this
case, maybe cardiac magnetic resonance (CMR) in
symptomatic patients with suspected CHD. Investigators found that noninvasive CMR resulted in a lower
probability of unnecessary angiography within 1
year compared to UK National Institute for Health
and Care Excellence [NICE] guideline-directed care.
CMR and myocardial perfusion scintigraphy
(MPS) strategies were similar in their ability to
prevent unnecessary angiography, and there were no
statistically significant differences in major cardiovascular adverse events at 1 year for all three strategies.
Current guidelines recommend angiography
for patients with stable chest pain based on their
pre-test likelihood for CHD. However, most of the
risk prediction models used have been around for
more than 3 decades and tend to overestimate risk,
thereby increasing the probability of invasive coronary angiography. Add to this the fact that most patients who undergo elective coronary angiography
– fully 60% in a recent large US study – are found to
have no obstructive CAD, and this makes reducing
unnecessary angiograms a good target for reducing
both patient procedural risk and costs.
The Clinical Evaluation of Magnetic Resonance
Imaging in Coronary Heart Disease 2 (CE-MARC 2)
trial included 1,202 patients with suspected CHD
from 6 United Kingdom centers. Patients were randomized to functional imaging-based investigation
with either CMR (n = 481) or MPS (n = 481), or
to NICE guideline-directed investigation (n = 240),
where only those with a high pre-test likelihood of
CHD are sent directly to angiography. Those with
a pre-test likelihood between 10% and 29% were
scheduled for cardiac computed tomography (CCT),
and those with a pre-test likelihood between 30% to
60% (intermediate risk) were scheduled for MPS.
Unnecessary angiography, defined by the
absence of significant stenosis measured by FFR
or quantitative coronary angiography, was seen in
28.8% of the group managed according to NICE
guidelines, compared to 7.5% of the CMR group,
and 7.1% of the MPS group (p < 0.001 for CMR vs.
NICE guidelines and p = 0.32 for CMR vs. MPS).
Overall, 22% of the study population underwent
coronary angiography within 12 months.
The CE-MARC 2 authors concluded, “Noninvasive functional imaging strategies reduced unnecessary angiography compared with guidelines-directed care.”
The investigators noted that MPS is the most
commonly used test worldwide for the assessment
of myocardial ischemia, with robust evidence supporting its prognostic value. However, their original
CE-MARC trial showed that CMR had a higher diagnostic accuracy compared to MPS4 and was also
a stronger predictor of risk for MACE.5 – JAMA n
REFERENCES
1. Danard I, et al. J Nucl Med. 2013;54:55-63.
2. Levine GN, et al. J Am Coll Cardiol. 2016;67:1235-50.
3. Lassen JF, et al. EuroIntervention. 2016;12:38-46
4. Greenwood JP. Lancet. 2012;379:453-60.
5. Greenwood JP. Annals of Internal Medicine. 2016 May 10.
[Epub ahead of print]
September/October 2016