Transcript Dr Robert Califf

Clinical Trial Commentary
SoS
Dr Eric Topol
Provost and Chief Academic Officer
Chairman and Professor, Department of Cardiology
Cleveland Clinic
Dr Robert Califf
Professor of Cardiology
Associate Vice Chancellor for
Clinical Research at Duke University
SoS
Study design
International study:
11 European countries and Canada
Trial design:
Comparing CABG and stent-assisted
angioplasty in patients with multivessel
disease.
Primary end point:
need for additional revascularizations
Secondary end point:
composite of death or nonfatal Q-wave
MI, and all-cause mortality.
SoS
Mortality rates: SoS
Mortality
PCI
(n=488)
CABG
(n=500)
All deaths reported*
4.1%
1.2%
All deaths at 1 year
2.5%
0.8%
* As of presentation at ACC 2001; p value = 0.007
SoS
An unexpected result
Some explanations for the finding:
CABG was remarkably well done
8 cancer deaths in the PCI arm skewed
the results
Repeat TVR was less surprising:
20.3% for PCI
5.8% for CABG
SoS
Mortality rate: ARTS
Mortality at 1
year
All deaths*
PCI
(n=600)
CABG
(n=605)
2.5%
2.8%
*p value = n/s
Serruys et al. N Engl J Med 2001; 344: 1117-24.
SoS
Response to the study
SoS has an imbalance in mortality risk
favoring bypass surgery.
The interventional cardiology community
largely ignored SoS, as if they dismissed it
because they didn’t like the data.
Topol
SoS
Confusing results
This reinforces my belief that the more
complicated the anatomy, the better CABG is
than PCI.
Nothing has convinced me that stenting will
fix that for PCI.
Stenting does reduce the number of repeat
revascularizations.
Califf
SoS
Plumbing
“I really do think that ultimately for bad multivessel disease it boils down to a matter of
plumbing -- how many open conduits do you
have? And it’s going to be pretty hard to beat
surgery in this regard.”
Dr Robert Califf
Professor of Cardiology
Associate Vice Chancellor for
Clinical Research at Duke University
SoS
Quality of surgery
The excess in cancer deaths is a fluke, but
the cardiovascular deaths still show the same
trend.
Surgical quality is critical, especially in
clinical trials.
The quality of the surgery isn’t consistent
across the globe.
Califf
SoS
CABG mortality
But this rate of first-operation mortality for
bypass, in the peri-1%, that's not so unusual
these days, is it?
Topol
For patients who qualify for PCI, it isn’t that
much of a surprise. I'll bet if you look at the
Cleveland Clinic, at patients like this, it's
considerably less than 1%. So I don't think the
trial is totally a fluke.
Califf
SoS
Small diabetic population
So few patients with insulin-dependent
diabetes makes the results even more striking.
Califf
There wasn't much in the way of IIb/IIIa
inhibitor use in the trial, which might have
neutralized some of the stent liability in
diabetics, but that wasn't the case.
Topol
SoS
RITA trial
RITA trial
mortality at 2.5 year follow-up:
3.6% for CABG
3.1% for PTCA
RITA was discounted by the interventional
cardiology community because they didn't like
the data.
SoS was rigorously done and the cancer
deaths don’t explain it away.
Topol
SoS
Pump head
SoS included a prospective assessment on
congnitive function.
Some have discounted surgery's success in the
trial because of “pump head.” (The patients
are alive but their brain isn’t working.)
Topol
SoS
Cognitive decline with CABG
Percentage of patients suffering decline in cognitive function
by >20% post-CABG compared to pre-CABG baseline
At discharge
53%
At 6 weeks
36%
At 6 months
24%
Newman et al. N Engl J Med 2001; 344: 395-402.
At 5 years
42%
SoS
Cognitive decline in SoS
I would be surprised if cognitive decline is a
factor.
Patients who are at highest risk for "pump
head" tend to be the worst candidates for PCI:
horrific atherosclerosis
LV dysfunction
elderly
Califf
SoS
MASS, ARTS, SoS
Three trials have not settled the question:
ARTS, SoS, MASS
Just stenting has not achieved parity in
outcomes.
The disparity in mortality remains troubling.
Topol
SoS
Putting it together
The studies need to be looked at side by
side, in an overview as well as separately.
Unfortunately, in this field, it hasn't been
done as effectively as it has been for other
medical therapies (eg BARI).
To this day, there still is not a by-patient
systematic overview of bypass surgery vs
angioplasty.
Califf
SoS
Best of both worlds.
“It seems to me that ultimately the two procedures
need to be combined. That there are probably
some vessels within a patient that would do just as
well with a stent, and there are others that perhaps
are ideal for off-pump bypass. And that somehow
combining those two, you ought to be able to get
the best of both worlds.”
Dr Robert Califf
Professor of Cardiology
Associate Vice Chancellor for
Clinical Research at Duke University
SoS
Hybrid procedure.
A hybrid procedure will be increasingly
popular.
Stenting will continue to get better, with
coated stents and with better adjunctive
medications.
Off-pump surgery, and ultimately even
percutaneous bypass might be possible.
Topol
SoS
Dichotomization
We only have three trials so far - it would be
hard to say that bypass surgery is the
treatment of choice for multivessel disease.
I don’t think the interventional cardiology
community is going to succumb just yet
Topol
There is some dichotomization due to tradeunionism, which I hope we can get over.
Califf
SoS
Surgery or stenting, who decides?
“In the best of all worlds it would be nice to have
an independent opinion. Ideally, it would be nice
if you had this really proficient angiographer who
didn't necessarily do interventions, or would be
able to review a cath without a bias, to be the
honest broker to make decisions. But we don't
have that.”
Dr Eric Topol
Provost and Chief Academic Officer
Chairman and Professor, Department of Cardiology
Cleveland Clinic
SoS
Enough for everyone
Operator experience is a factor, some of the
most experienced operators tend to be very
aggressive.
Topol
With the aging population, there should be
enough business for everyone. There should be
a more rational system to have the right patient
get the right procedure.
Califf
SoS
SoS trial review
Dr Robert Califf
One thumb up
"We need to see the
final data;
particularly the
quality-of-life data."
SoS
SoS trial review
Dr Eric Topol
Two thumbs up
“Well done, wellpresented, and just
the kind of trial we
need.”