OPtimal stEnt deployment stRategy oF Contemporary sTents

Historically, when coronary stents were initially introduced in the late 1980*s
and up until the 1990*s, the standard and mandatory standard treatment of a
significant stenosis was with pre-dilation prior to stent placement.
Predilatation has the benefit of cracking the hardest, most calcific parts of
the plaque, as well as providing information on the lesion length and vessel
diameter. Thus improving proper size selection of the stent. After stent
implantation, an additional postdilatation could be performed in order to
improve and maximize stent diameter and expansion.

This standard routine changed in the early 2000s when a technique called
*direct stenting* (DS) was pioneered. In DS, no predilatation was performed to
crack the plaque and test the lesion length and vessel diameter. Instead, after
coronary angiography, a stent was selected and directly placed over the
stenosis. The landmark ISAR-DIRECT trial1 was conducted in 2000 and found no
difference in clinical outcomes as death, myocardial infarction and restenosis
between two different stent implantation techniques: direct stenting (DS)
versus conventional stenting after pre-dilation (CS). Various studies in the
2000s demonstrated similar results; DS has been considered a safe and effective
treatment in patients who undergo percutaneous coronary intervention (PCI) 1-4
and may reduce contrast use, procedure time and costs compared to the more
labor intensive CS5. However, DS also has some potential disadvantages that
might increase procedural risks and may lead to suboptimal clinical results. A
higher risk of failure to initially cross the lesion, errors in stent
placement, incorrect stent sizing, underexpansion, stent dislodgment, and
embolization are among the complications of DS.

These stent implantation technique trials of the early 2000s led to a clinical
reality which continues until today, in which coronary stent implantation has
become *unprotocolized*, i.e. each operator has his/her own, individual and
fairly subjective experience and reasons for applying or avoiding pre- and
post-dilation in specific conditions. However, the results of these trials do
not apply to the modern clinical practice of coronary stenting. First, the
current patient population undergoing PCI cannot be compared to the population
that was treated in the early 2000s. Patients today are significantly older,
have more comorbidity such as diabetes, prior PCI and consequently present with
much more complex coronary anatomy and more advanced atherosclerosis1,6.
Secondly, stents have undergone several major transformations in the last 20
years. Stent metal alloys and architecture have improved and strut thickness
has been reduced. Stents can now be delivered to complex anatomies which could
not be treated in the early 2000s. In addition, current stents are
drug-eluting, which prevents in-stent restenosis1,6. Because of the better
stent design and improved background pharmacological therapy, event rates of
death and myocardial infarction (MI) after PCI have significantly decreased
within in the last decades. One-year event rates of approximately 20 % in
ISAR-DIRECT have now been reduced to approximately 6 %, as we have recently
reported in the follow-up of 8137 PCI patients1,6. The non-significant
differences in major adverse cardiac events (MACE) of 2-3% between DS and CS
arms in the old trials1-4 are considered clinically highly significant in
contemporary clinical practice.


Advances in intracoronary imaging, such a highly detailed coronary imaging
technique called Optical Coherence Tomography (OCT), have revealed that an
optimal stent result is not achieved in a high percentage (up to 31%) of the
stent implantations7. However suboptimal stent placement was already present
with one of the ten different OCT criteria. Nevertheless suboptimal stent
implantation results in a 3.5-fold increased risk of death, myocardial
infarction (MI) or target lesion revascularization (TLR) within one-year
follow-up of the observational CLI-OPCI II study 7(MACE rate of 25.2% with
suboptimal versus 7.1% risk at optimal stent result). As a consequence, there
is an urgent need to revisit the optimal stent implantation technique.

Contemporary coronary stents are based on metallic alloys. In the past decades
however a different concept of non-metallic so-called bioresorbable stents
(BRS) was developed, introduced and subsequently abandoned due to an increase
in MACE, primarily of stent thrombosis and MI. Intriguingly, one of the major
lessons learned from this past BRS era is that optimization of the implantation
technique with predilatation and postdilatation could reduce adverse cardiac
events over time8-10 . As a result of these findings, the PSP concept:
Pre-dilation, Sizing and Post-dilation was introduced and highly recommended
for BRS. Post-hoc studies revealed a reduced risk of cardiac death, MI and
revascularization when the PSP technique was used in BRS11. Whether routine
pre- and postdilatation compared to DS also results in optimal stent
implantation in modern metallic drug-eluting stents (DES) has not been
investigated and, hence is currently unknown.

A prior hypothesis: we hypothesize that the PSP technique will be superior to
DS technique in optimal stent placement in patients with stable angina pectoris
(SAP) receiving DES. Additionally, we hypothesize that the PSP technique has a
lower risk on cardiovascular events compared to DS technique in patients with
SAP.

Primary objective
The primary objective is to evaluate whether a standard pre- and postdilatation
of the modern DES results in a more optimal stent implantation compared to DS
as evaluated by OCT in patients with stable coronary artery disease.
Secondary objective
The secondary objective is to evaluate clinical cardiovascular outcomes in
patients with stable coronary artery disease.

This study is a prospective, single-blind clinical study, randomizing patients
to PSP implantation technique vs direct stenting technique in a 1:1 ratio. The
clinical investigation will be conducted in the Albert Schweitzer hospital,
Dordrecht, the Netherlands.

Patients are treated according to the randomized regimen from the day of
randomization till the last planned staged PCI procedure for all lesions.
Patients will be kept blinded for the randomization arm till the end of the
study. At the end of the study patients will be informed about the results.
There are no restrictions in number of target lesions.

Randomization to PSP treatment
If the patient is randomized to the PSP treatment arm, the procedure will be
performed
following the PSP protocol. The definitions of the PSP technique are:
• Predilatation is mandatory with a balloon diameter equal to or maximally 0.5
mm less than the distal reference vessel diameter. We hypothesize that this
lesion preparation and fracture of the calcium may result in better stent
apposition, less recoil and higher minimal stent area (MSA) Also see endpoints.
• The DES should be deployed at 2 atm. above the nominal pressure. This
relatively low stent deployment pressure may prevent stent edge dissections.
• The postdilatation is mandatory with a shorter length and (at least 0.25mm)
larger diameter non-compliant balloon at 16 atm. The apposition, minimal stent
area (MSA) and recoil may improve with this large, high pressure
postdilatation. The slightly shorter balloon can prevent edge dissections.

OCT will be performed at the end of the procedure.

Randomization to direct stenting treatment
• The DES is directly placed without any lesion preparation and deployed at a
pressure at the discretion of the operator. Ideally a pressure would be
achieved in which angiographic expansion of the DES is complete (without
significant dog-boning)
• In certain instances, the operator will not be satisfied with the
angiographic appearance after DS and would like to perform an additional *bail-
out* postdilatation. Ideally, this should not occur, but cannot be avoided in
certain cases to achieve an optimal treatment for the patient. In this
situation (expected to occur in maximal 30 % of the DS arm) the patient, who
has already provided informed consent and has been randomized, will be
transferred to a third arm, the so-called PERFECT PSP registry arm. Excluding
these patients from the DS arm is the most robust method of purely
investigating the difference between PSP and DS (without additional
manipulations). These cases will be accounted for in the block randomization

Use of co-intervention
Decisions of the usage of guidance (like FFR/ iFR, RFR) pre-PCI and usage of
medication during the procedure is left at the discretion of the operator.

Multivessel PCI
If a lesion is not suitable for direct stenting, it is allowed to treat this
lesion during the index procedure. These non-randomized lesions must be treated
prior to randomization and must have been successful and uncomplicated (defined
more stringently as angiographic diameter stenosis 5 minutes) or prolonged
ST-segment elevation or depression (>5 minutes), or cardiac arrest or need for
defibrillation or cardioversion or hypotension/heart failure requiring
mechanical or intravenous hemodynamic support or intubation).

Complication rate of control OCT measurement is low, and complications are
self-limiting or easily treatable. Therefore, this study is classified as
negligible risk research, according to the NFU risk classification. The
additional imaging with OCT may benefit the patients enrolled in the study.
Post-PCI imaging allows to detect and treat sub optimal results, such as edge
dissections, tissue protrusion or under-expansion.