A single-arm trial to evaluate the effectiveness of PCI of de novo 3-vessel disease
applying the SYNTAX Score II with pressure wire functional assessment and
IVUS guidance, using an everolimus-eluting stent with biodegradable abluminal
coating

The anatomical-based SYNTAX Score I has established itself as a tool to aid the
Heart Team consensus in determining the optimal revascularization modality by
examining the coronary angiogram in patients with unprotected left main
coronary artery (ULMCA) disease or de novo three vessel disease (3VD).

A recent study pooling over 6000 PCI subjects treated with drug-eluting stents
(DES), demonstrated that the addition of clinical variables to the SYNTAX Score
I, substantially increased the accuracy of identifying low (and high) risk
patients compared to the SYNTAX Score I alone. In addition, newer generation
coronary drug eluting stents have proven reductions in stent thrombosis and
other clinical outcomes compared to SYNTAX trial.

The SYNTAX Score II was designed to improve decision making between CABG and
PCI, by allowing for a long term, individualized risk assessment of patients
with complex coronary artery disease. The SYNTAX Score II combined the
anatomical based SYNTAX Score with clinical variables, that were shown to alter
the threshold value of the SYNTAX Score so that equipoise was achieved between
CABG and PCI for long term mortality. SYNTAX Score II was developed in the RCT
SYNTAX trial (n= 1800) and validated in the DELTA Registry (n= 2891)

A large body of evidence, largely based on the use of fractional flow reserve
(FFR), has demonstrated that, compared with angiography, decision making of
coronary revascularisation based on physiological assessment of stenosis
severity results in improved patient outcomes. Recalculation of the SYNTAX
score by incorporating FFR-derived information of stenosis severity (functional
SYNTAX score40) may decrease the number of higher-risk patients with
multivessel disease undergoing PCI and contribute to a better discrimination of
risk for adverse events in this subset of patients. A new pressure-derived
index, instantaneous wave-free ratio (iFR), that allows faster adenosine-free
assessment may be more ideally suited for multiple measurements performed in
the context of multivessel disease.

Use of IVUS was mainly promoted in bare-metal stent era to tackle restenosis
and was less used after arrival on the market of drug eluting stents (DES).
Recent meta-analysis of nearly 20.000 patients has reported significant
reductions of stent thrombosis and mortality after IVUS-guided DES
implantation. This suggests that IVUS guidance in complex patients may
contribute to better patient outcome.

* To evaluate the effectiveness of contemporary PCI treatment of de novo
3-vessel disease following the heart team selection applying the
SYNTAX Score II with pressure wire functional assessment and IVUS
guidance (SYNTAX II strategy).
* To establish superiority of the SYNTAX II strategy compared to the PCI arm of
the SYNTAX I study (Primary Endpoint).
* To prospectively assess the effectiveness of SYNTAX Score II for heart team
decision making.
* To prospectively validate the SYNTAX Score II for all-cause death at 1 and 2
year and 5 year follow-up.
* To retrospectively validate the residual SYNTAX Score (academic research)

The SYNTAX-II Trial is a multicenter, 3-vessel disease, all-comers, open-label,
single arm trial of approximately 450 patients in approximately 25
interventional cardiology centres in Europe. All patients will be treated with
the Boston Scientific SYNERGY* Everolimus-Eluting Platinum Chromium Coronary
Stent System.

Risks are no different than the risks of standard PCI procedure nor for the use
of the imaging techniques, iFR/FFR and IVUS.