EDITOR’S CORNER
Peter C. Block
Editor-in-Chief, CardioSource WorldNews: Interventions
Do New Trial Data From
ESC Support BMS Redux?
I
n the April/May edition of Cardiosource World
News Interventions, I wrote an editorial asking
whether bare metal stents (BMS) should, or could
be eliminated from cath lab inventory. The discussion
at that time centered on two studies – the ZEUS and
the LEADERS-FREE trials. The ZEUS trial showed
that in patients with high bleeding risk and in of need
coronary stenting, dual anti-platelet therapy (DAPT)
for 30 days had greater safety and efficacy in patients
who were treated with drug-eluting stents (DES) rather
than BMS. All trials have cautions attached, and ZEUS
is no exception. ZEUS was not conducted with contemporary stent platforms, so broad-brush conclusions
are not possible. The LEADERS-FREE trial compared
a polymer-free drug coated stent using umirolimus to
a similar BMS in patients with high bleeding risk. All
patients were mandated to have only 1 month of DAPT.
A composite primary end point (cardiac death, myocardial infarction, or stent thrombosis) (9.4% vs. 12.9% in
the DES group and BMS groups respectively) showed
non-inferiority. But in LEADERS-FREE, need for target
lesion revascularization was less in the DES group
(5.9% vs. 9.8%). The conclusions: DES was superior to
a BMS with respect to safety and efficacy endpoints.
Thus, in that editorial I asked a question, and added a
codicil: “Nonetheless, with the supportive data from
LEADERS-FREE, is it time to finally be rid of BMS on
interventional shelves? With mounting evidence that
even patients with high bleeding risk are better served
with a DES than a BMS, and DAPT is only needed for
30 days, perhaps it is time to agree BMS are not needed
any longer even for those patients that might have
benefitted. But then again, there are those patients who
steadfastly refuse to take DAPT, or cannot afford it.” I
should have added: “And, arguably, are at high bleeding
risk, or need surgery that cannot be delayed.”
At the European Society of Cardiology Congress held
in Rome in August, two new trials were reported that
shed further light, and perhaps some confusion, on
the discussion of BMS vs. DES. The first, and superficially most contrary to the pro-DES argument is the
NORSTENT Trial (1). NORSTENT compared long term
effects of a new generation DES with a contemporary
BMS in more than 9,000 patients with stable or unstable
angina and followed the outcomes for 6 years. The
major endpoints were mortality, morbidity, and target
vessel revascularization. The short version of the results
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CardioSource WorldNews: Interventions
is that there was no difference in the primary endpoint
(death or non-fatal myocardial infarction) between the
two groups. Death from any cause and nonfatal myocardial infarction was almost identical: 16.6% in the DES
vs. 17.1% in the BMS patients. Multiple adjustments
for baseline differences (e.g. smoking status, hypertension, history of myocardial infarction, target-lesion type,
total stent length, lesion and procedural characteristics)
yielded the same results. However, at 6 years the DES
group had fewer revascularization procedures (driven by
target lesion revascularization) at 16.5% vs. 19.8%. Interestingly, rates of stent thrombosis were extremely low at
0.8% and 1.2% in the DES and BMS groups respectively.
What does this study add to the discussion of DES
vs. BMS? At first glance it might appear to support
the notion that BMS and DES are alike, so why not go
with the less expensive BMS? But I do not think t hat
is correct. Coronary stents were developed to counter
the complications of “plain old balloon angioplasty”
(POBA). Though primitive, the first stents actually did a
good job in avoiding urgent/emergent coronary surgery
that was so often needed after a POBA. It was stents
that finally erased the concept of “surgical standby.” As
stents improved in design they were routinely used to
enhance the results of POBA, cover local coronary dissections, and help reverse sudden coronary occlusions.
In doing so, stents actually further damage the vessel
media, enhancing smooth muscle cell proliferation and
restenosis. DES then helped solve that problem by inhibiting cellular ingrowth. Thus, it comes as no surprise
that the mortality and MI outcomes of DES vs. BMS are
similar. Both DES and BMS perform admirably in the
short setting of a PCI. It’s the long term differences that
result in DES superiority. Restenosis, resulting in need
for repeat revascularization is the downside of BMS. It
is a slow process and mostly causes recurrent symptoms before acute MI and/or death. The NORSTENT
Trial confirms that notion, and further supports the fact
that need for vessel revascularization is more common
with BMS. Rather than raising the question that we
ought to reconsider BMS when stenting, the data actually support the use of DES to avoid repeat procedures
and more healthcare resources. If BMS and DES were
equal in cost and both could be used in patients with
high bleeding risk, I bet that almost all stenting procedures would/should be done with DES.
But this is not an all-or-none argument. BMS might
be just fine for large vessel PCI since intimal ingrowth
is not so much a risk. For patients with bleeding risk,
need for urgent surgery, or those in atrial fibrillation
where triple therapy clearly increases bleeding risk,
the argument for BMS vs. DES simply does not have
enough data support to favor one over the other, though
BMS will have a higher need for repeat revascularization. To complicate the argument further, DES do have
slower endothelialization rates than BMS and therefore
a low, but real late thrombosis risk. So the discussion
continues, but the argument in favor of continuing to
use BMS is steadily losing ground. BMS are a minority
player, and will continue to be so.
To further bolster the pro-DES argument, the BASKETSAVAGE Trial, also presented at ESC showed that DES
are clearly superior to BMS in PCI of saphenous vein
grafts (SVG). The randomized BASKET-SAVAGE Trial
was to include 240 patients with SVG disease. The
trial was stopped at 173 patients. At 12 months major
adverse cardiac events had occurred in 18% of BMS vs.
2.3% of DES patients. At 3 years 30% of BMS patients
had a major cardiac event, compared to 12.4% of DES
patients (the outcome driven by target vessel revascularization, since cardiac deaths were similar in both groups).
The trial is a small one, and the devices studied are no
longer in use, making sweeping statements unrealistic,
but the large differences in the DES and BMS groups do
appear to strongly favor DES in SVG interventions. Other
trials are currently underway to compare DES and BMS
in SVG, but of note is that DES for SVG interventions are
already a Class 1A recommendation in ESC guidelines.
So where does the argument stand? If we only had
BMS and no DES, interventional cardiology would be
in a bad place. We would indeed use antiplatelet agents
for a shorter period of time, but at the cost of a lot
more revascularization procedures. If we only had DES
and no BMS, we would also be decreasing the length of
antiplatelet use. We would also know that in the long
term revascularization procedures would be fewer. It
would be pretty much business as usual (and as most
of us are currently practicing). Add to that a final question: “If they were the same price, would we really miss
not having BMS? I doubt it. ■
Peter C. Block, MD, is a professor of medicine and
cardiology at Emory University Hospital and School
of Medicine in Atlanta.
September/October 2016