The Syntax Trial:
PCI versus CABG
K. Eckland, ACNP-BC, MSN, RN
Heart & Vascular Center of Northern
Arizona
Flagstaff, Arizona
2011 was a hard year..
for cardiology..
• In the middle of this tumultuous time, the
latest results from the Syntax Trial were
released.
The Syntax Trial
•
-
Objectives:
What is it?
Purpose
The syntax score(s)
Considerations
Results
Syntax Trial
• Large scale study designed by a team of
cardiologists involving 1800 patients
randomized to receive either PCI or CABG for
multi-vessel and/or left main disease.
Purpose(s)
-(stated)
- to determine or attempt to prove the
‘non-inferiority’ of multi-vessel stenting, and
stenting of patients with left main disease versus
the gold standard (CABG)
-(unstated)
to defend the current cardiology
practices of placing multiple stents in patients who
would have previously been referred for definitive
treatment.
Rastan, A. J. & Mohr, F. W. (2011). Editorial: Three years after SYNTAX trial –
change in practice? European Journal of cardiothoracic surgery 40 (2011) 12791281.
Additional Areas of Study
• Comparison of results of PCI versus CABG in
specific subpopulations:
- Diabetics
- Left main disease
- ‘elderly’ patients
The Syntax Score
In order to compare groups of patients – (and
their disease burdens), the researchers came
up with a grading system which assigned a
numerical value to the amount of CAD seen
on cardiac cath.
Syntax Score
• The ‘Syntax Score’ is an overly complicated
grading scheme devised by cardiologists to
replace traditional criteria for stratifying
patients for PCI versus surgery.
• Syntax scoring attaches a numerical score to
degree of blockages on cath by length,
appearance and location.
• This means that a ‘tight’ left main is not a
tight left main – and very similar cases are not
considered comparable (by this method).
Syntax Score: 34
• A syntax score of ‘34’ was previously identified as
the point where patients should have CABG instead
of PCI in related works.
• For this trial – average score was 24 for PCI,
• 30 for CABG.
Tight left main,
bifurcation lesion,
With heavy
calcification
Syntax score?
Image taken from Sianos et. al. (2008). The Syntax Score: an angiographic tool.
However…
• Analysis of data showed Syntax score poor predictor
of mortality and outcomes.
So…
The ‘Clinical Syntax Score’ (CSS) was invented (Garg et.
al)
Combined the Syntax Score with modified ACEF factors to
create a mathematically-derived score
Modified ACEF = age, ejection fraction, and creatinine clearance
Garg, et al. (2010). Circ Cardiovasc Interv. 2010; 3: 317 – 326.
In addition,
• Questions about validity of study design/
ethics of study
• Weakest of possible RCTS (versus superiority
trials, and equivalence trial designs)
• Non-inferior trials do NOT actually prove/
demonstrate or show non-inferiority to the
comparison treatment. (ie. doesn’t really
compare PCI against CABG).
Mantovani et al.
• In fact, superiority trials are gold standard,
and are actually less expensive than ‘noninferiority’ trials.
• The aim of these trials is to declare new
treatment ‘acceptable’ not to show
improvement over current treatments.
• Trial design first used by drug companies to
get permission to market new drugs.
Other Considerations: Ethics
• Is it ethical or even possible to consent
patients for trials such as Syntax?
- Side note: in your experiences with patients
undergoing PCI/CABG – how well do you think
they really understand the disease, outcomes,
options?
Ethics of Syntax
• Robinson et. Al (2005) questioned the capacity of the lay
public to give informed consent for experiment
treatment and conducted nine different studies to
explore this idea.
• Specifically, they asked, “Do members of the public
understand and accept randomization?”
- majority of public could recognize randomization when
given study designs, however – most judged that these
methods were unacceptable in a trial context.
Robinson et. Al. (2205) Lay public’s understanding of equipoise and
randomization in randomized controlled trials. Health Technology Assessment,
2005; 9(8)
Robinson et. al continued
• They asked the participants if they believed that the
doctors really had equipoise regarding different
treatments in a study.
• - about half of the participants didn’t believe that
doctors could be unsure about the best treatment.
• Despite augmenting standard written explanations of
trials provided as part of informed consent –
researchers found that the lay public could not fully
understand concepts required for actual informed
consent.
Ethics & Syntax
• Mantovani, et. al (2010) had more specific
comments on the ethical behaviors of the Syntax
trial.
• Even title of study misleading since trial designed
on a ‘non-inferiority’ margin of 6.6%
This means researchers were willing to accept a
30% higher rate of death or severe adverse
effects and call it “Equal”. (when in fact, equal is
actual a designation higher than ‘non-inferior’.)
Mantovani et. al (2010). Non-inferiority randomized trials, an issue between
science and ethics: the case of the SYNTAX study. Scandinavian Cardiovascular
Journal, 2010; 44:321-324.
Mantovani et. al continued
• Luckily? PCI patients in the trial experienced
an even HIGHER rate of adverse events
(otherwise study designers and proponents
would be declaring victory for PCI.)
Mantovani et al.
“In our opinion, the Syntax study disregarded
the safety of the patients, by including death
and major complications of a primary endpoint of a non-inferiority study.”
The Study: Results
CABG SUPERIOR in all areas: LIFE
Lower mortality with CABG – cardiac death only 3.6%
at 3 years for CABG vs 6.0% with PCI
- Less major adverse events 20.2% cabg vs 28% PCI
These results confirmed previous studies.
Preliminary results reported prior to 2011 as well as several other, smaller studies
Results continued
CABG SUPERIOR: Efficacy
Patients with CABG required less re-interventions
10.7 % versus 19.7% in PCI group.
- Less MIs in CABG group: 3.6% versus 7.1% (31
people vs 62 people**).
- Patients with CABG reported less angina
CABG relieves angina better than PCI. Family Practice News; July 12, 2009.
•In CABG group – 4 pts with MI after randomization but prior to surgery, 22 occurred
within 7 days of CABG.
• In PCI – 2 before tx, 30 MIs within 7 days.
Syntax Results: Efficacy
Graft occlusion versus stent thrombosis
• - 26 graft occlusions in CABG arm – 6 patients had
MI, and 17 patients required revascularization.
None died.
• 36 patients with stent thrombosis* – 11 died.
14 patients revascularized
*all but four patients in PCI group on Dual antiplatelet
therapy.
The Study Results
CABG SUPERIOR : $$ Cost $$$
The overall costs for bypass surgery are less than
the cost of PCI.
The average patient randomized to the PCI arm
received 4.6 stents.
Among Special Populations:
CABG Superior:
- the treatment of left main disease
- For treatment of CAD in Diabetic
- For treatment of CAD in the elderly
population.
- Even for patients with low Syntax scores..
Syntax Trial Results
Rate of peri-operative/ post-operative stroke
was initially higher in CABG patients, but
results equalized three years into the study with no significant different (PCI 2.0% versus
2.2% with CABG.)
- This also does not take into account that in the
‘real world’, more surgeons are doing offpump surgery which reduces risk of CVA.
Syntax Trial
• “4-year data from the SYNTAX trial showed, a
divergence in death rates between the patients
who were treated with bypass surgery and
those who underwent PCI with a Taxus stent.
All-cause mortality and cardiac death were
both significantly higher in the PCI group
compared with the surgery group, as was MI,
and the excess rate of strokes initially observed
in the CABG group has now leveled out.”
- presentation at the European Assoc of
Cardiothoracic Surgery, October 25, 2011
Syntax Results
As a result of these findings – new
‘revascularization guidelines’ released last
week.
- Collaborative work between cardiologists and
cardiac surgeons.
- Has recommendations for who/ when/ what
circumstances people should receive PCI and
when CABG is indicated.
Appropriate Use Ratings for Revascularization in Acute Coronary Syndromes*
American College of Cardiology Foundation Appropriate Use Criteria Task Force, et al. J Am Coll
Cardiol 2012;0:j.jacc.2011.12.001v1-S0735109711050972
Copyright ©2012 American College of Cardiology Foundation. Restrictions may apply.
Why this matters
• The public perception of stents as the ‘easy
option’
• Limited ability for public
to read/ understand/
comprehend medical
research.