Coronary Artery Disease Clinical Trial
Official title:
Rationale and Design of a Prospective, Open Label, Randomized, Multicentric Clinical Trial: Drug Coated Balloon for Side Branch Treatment vs. Conventional Approach in True Bifurcation Coronary Disease: PRO-DAVID
Bifurcation lesions (BL) on coronary arteries account for 15-20 % of all performed
percutaneous coronary interventions (PCI). Preferred approach for treatment of most
bifurcation lesions is the stepwise provisional stent strategy with main branch-only stenting
followed by provisional balloon angioplasty with or without stenting of the side branch (SB).
Stenting of the side branch is indicated when the angiographic result in SB is clearly
suboptimal and when flow remains reduced. Upfront use of two stent techniques may be
indicated in very complex lesions with large calcified side branches ( most likely to supply
at least 10% of fractional myocardial mass), with a long ostial side branch lesion (>5mm) or
anticipated difficulty in accessing an important side branch after main branch stenting, and
true distal LM bifurcations.
From a technical point of view, we propose a "Provisional DCB approach" that differs from the
standard provisional approach with obligatory SB predilation and good lesion preparation. In
case of an adequate result of predilation, the procedure on the SB ends with the DCB
deployment. This is followed by main branch stenting with DES, finished with POT. Final
'kissing' balloon dilation is generally not recommended because there is no advantage from
final kissing with the one-stent technique. With this approach, there is no need for
re-wiring, re-ballooning, side branching and wire jailing and final kissing. This technique
is close to a contemporary approach to bifurcation lesions based on the fundamental
philosophy of the European Bifurcation Club (EBC): keep it simple, systematic, and safe, with
a limited number of stents that should be well apposed and expanded with limited overlap,
with respect of the original bifurcation anatomy.
Bifurcation lesions (BL) on coronary arteries account for 15-20 % of all performed
percutaneous coronary interventions (PCI). Preferred approach for treatment of most
bifurcation lesions is the stepwise provisional stent strategy with main branch-only stenting
followed by provisional balloon angioplasty with or without stenting of the side branch (SB).
Stenting of the side branch is indicated when the angiographic result in SB is clearly
suboptimal and when flow remains reduced. Upfront use of two stent techniques may be
indicated in very complex lesions with large calcified side branches ( most likely to supply
at least 10% of fractional myocardial mass), with a long ostial side branch lesion (>5mm) or
anticipated difficulty in accessing an important side branch after main branch stenting, and
true distal LM bifurcations.
For non-left main bifurcation lesions consensus is that there is no systematic advantage to a
more complex dual-stent implantation technique. For true left main lesions EAPCI/EACTS
revascularization guidelines gave a IIb recommendation for double-kissing crush two-stent
strategy compared to the provisional approach, based on the results of DKCRUSH-V Trial. EBC
perspectives, even for the stenting on left main coronary true bifurcation lesions, is that
they are best treated with a planned single-stent strategy rather than a planned dual-stent
strategy. When a two-stent strategy is used, this will become apparent during a provisional
stepwise approach, and finalizing the procedure using a culotte technique or occasionally TAP
is recommended.
PCI strategies for complex coronary bifurcation lesions should be individualized, taking into
account the anatomical differentiation of coronary bifurcation lesion differences, disease
burden and complexity, but also the technical skills and experience of the operator. In daily
clinical practice where less experienced operators with limited number of true bifurcations
annually are faced with the challenge of treating complex bifurcation lesions, it is
imperative to find a standardized and universal approach which would be simple, quick and
safe, with a high percentage of procedural success, with a small number of complications,
good long term results, with small expenditure of material and contrast volumes, and shorter
procedure and fluoroscopy times.
Drug-coated balloon (DCB) technology allows to bring high concentration of an
antiproliferative drug with immediate and rapid local delivery even with short contact times
between the balloon surface and the vessel wall, sufficient for effective drug delivery
without a durable polymer and further permanent metal prosthesis. The application of DCB in
SB is an attractive and intriguing solution in treating complex BL. Rationality of such an
approach lies in the many theoretical advantages of DCB. The application of DCB in SB
respects the original anatomy of bifurcation, which is especially important in the carina
area, and allows for the homogeneous application of a high dose of antiproliferative drug on
the entire blood vessel surface and avoids the risk of incomplete coverage of the bifurcation
area. In the case of a successful DCB application in the SB, unnecessary use of the stent is
avoided, obviating long-term problems such as stent malposition and fracturing, scaffolding
of the SB ostium, overlapping and crushing of multiple metal layers and polymers with
uncontrolled drug release, and therefore re-stenosis and thrombosis and reactions to a
foreign body. Even for the simplest provisional technique, the application of DCB has a
theoretical advantage over the application of a regular balloon, with the expected positive
remodelling of the vessel and plaque stabilization, and better late angiographic results, as
well as neoatherosclerosis.
From a technical point of view, we propose a "Provisional DCB approach" that differs from the
standard provisional approach with obligatory SB predilation and good lesion preparation. In
case of an adequate result of predilation, the procedure on the SB ends with the DCB
deployment. This is followed by main branch stenting with DES, finished with POT. Final
'kissing' balloon dilation is generally not recommended because there is no advantage from
final kissing with the one-stent technique. With this approach, there is no need for
re-wiring, re-ballooning, side branching and wire jailing and final kissing. This technique
is close to a contemporary approach to bifurcation lesions based on the fundamental
philosophy of the European Bifurcation Club (EBC): keep it simple, systematic, and safe, with
a limited number of stents that should be well apposed and expanded with limited overlap,
with respect of the original bifurcation anatomy.
The study hypothesis is that in patients with true complex bifurcation lesions (Medina 1,1,1;
1,0,1; 0,1,1) with significant SB, intervention using DCB first in SB and DES in the main
vessel will not be inferior then planned single-stent strategy treating with superiority in
the simplicity of procedure.
The registry will include patients requiring percutaneous coronary interventions with true
bifurcation lesions (Medina 1,1,1; 1,0,1; 0,1,1) of unprotected left main coronary
bifurcation disease, and non left main bifurcational lesion with affected important side
branches most likely to supply at least 10% of fractional myocardial mass. The SYNTAX score
for the lesions that are to be treated should be <32.
Patients who fulfill inclusion and exclusion criteria and consent to the study will be
randomized according to a standard random number generation method. Patient randomisation
will be stratified by participating centre.
A diagnostic coronary angiography will be performed on all patients who have the clinical
criteria for inclusion into the trial. All of the procedures will be carried out by classical
radial or femoral approach depending on the operator choice, and the intervention will be
carried out ad hoc or electively, at the operator discretion. Before the PCI procedure the
patients will receive 300 mg of acetylsalicylic acid (100 mg if they were saturated earlier)
600 mg clopidogrel (75 mg if they were saturated earlier), or 2 x 90 mg ticagrelor and
unfractionated heparin 70 - 100 UI/kg of body weight. The administration of intergrilin is
upon operator decision. After intracoronary application of 100-200 µg of nitroglycerin a
diagnostic angiogram will be carried out to record several views from various angles to
obtain an optimal angiographic view that allows the visualization of branch division as well
as the measurement of angles and assessment of the degree of ostial SB stenosis , "the
working view". Planned single- and dual-stent techniques will be performed according to the
recommendation of the EBC consensus.
The patients will be randomized in one of two groups including standard provisional approach
or provisional DBC approach.
Standard provisional approach technique:
Coronary guidewires should be passed to the both main branch ( MB ) and side branch ( SB )
vessels. MB preparation should be considered routine practice in stable patients, but initial
SB predilatation is only recommended when access is difficult, in cases of severe diffuse
and/or calcified SB lesion or compromised SB flow after wiring. Stenting of the main vessel
should be undertaken with a wire jailed in the side vessel to preserve side vessel flow and
access. Second-generation DES should be used and stent diameter should be chosen according to
the size of the MB beyond the bifurcation, and according to the expansion ability of the
stent in proximal MB with proximal optimisation technique ( POT ). Following stenting of the
MB, POT should be performed routinely with a short appropriately sized non-compliant balloon.
Following POT, rewiring of the SB should aim to recross a distal stent cell. KBI should be
performed using two NC balloons, sized according to the actual reference size of the vessels
or 0.5 mm below, with individual high-pressure inflation followed by a final lower-pressure
kiss dilatation. The procedure should be finalised by POT after kissing to correct the
proximal MB stent distortion. SB should not be treated further unless there is one of the
following: TIMI flow <3 in the SB, severe ostial pinching of SB(>90%), threatened SB closure,
SB vessel dissection >type A, or FFR > 0,80. Bail-out SB stenting after MB stenting is
performed with T-stenting, T and protrusion ( TAP ) or culotte. Implantation technique is
selected according to angulations, reference size differences and operator capabilities. If
SB stenting is necessary, it should be followed by KBI, and the procedure should be finalised
with a second POT
Provisional DCB approach:
Wiring of MB and SB and MB preparation is the same as in standard provisional approach.
Initial SB predilatation is obligatory. Predilatation of SB is done with semicompliant or
noncompliant balloon, with balloon to vessel ratio of 0.8-1:1 at nominal inflation pressures.
Liberal use of scoring or cutting balloons sized 0.5 mm smaller than the vessel size and
inflated to high pressure is also recommended. Angio check is repeated after 10 minutes and
intracoronary nitroglycerin application to rule out acute recoil. DCB is inflated in SB only
after successful predilatation defined as residual stenosis ≤ 30% and no C,D,E,F dissection.
Manipulation of the DCB should be done in the way to avoid drug loss during transit : no
manipulation during flushing, lesion site should be reached rapidly, care should be taken
when crossing the Y-connector and navigating through the proximal coronary artery up to the
lesion. Inflation time when applying a DCB is 60 s, using DCB to vessel ratio of 0.8-1:1 at
low inflation pressures that should not exceed nominal pressure, to reduce the risk of
dissection. DCB inflation in SB is followed by a DES deployment in the main branch. POT is
mandatory, and a final kissing balloon or POT/side/POT is not done.
Bail out stenting of SB could be done at two points of the procedure. First decision on the
need for bail out SB stenting is after predilatation of SB and angio check. Bail out stenting
is indicated in case of unsuccessful SB predilatation ( dissection C,D,E,F, or residual
stenosis >30% ) or in case of decreased flow-TIMI <3, acute recoil, ischemia or FFR > 0,80.
Bail-out SB stenting can be performed with any two stent technique. Implantation technique is
selected according to angulations, reference size differences and operator capabilities,
followed by KBI, and the procedure should be finalised with a second POT. After deployment of
DCB and POT, there is second decision to perform bail out SB stenting. Here it is indicated
in SB pinching ≥ 90% stenosis or FFR > 0,80 , dissection >type A, threatened SB closure,
decreased flow - TIMI <3 or ischemia. Bail-out SB stenting after MB stenting is performed
with T-stenting, T and protrusion ( TAP ) or culotte. Implantation technique is selected
according to angulations, reference size differences and operator capabilities. If SB
stenting is necessary, it should be followed by KBI, and the procedure should be finalised
with a second POT.
Patients will be followed up by telephone or in person 1, 6, 12 and 36 months, and optional
angiographical control after 9 months.
Significant symptoms will trigger further investigation as required.
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