SoS

Clinical Trial Commentary

Dr Eric TopolProvost and Chief Academic OfficerChairman and Professor, Department of CardiologyCleveland Clinic

Dr Robert CaliffProfessor of Cardiology Associate Vice Chancellor for Clinical Research at Duke University

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

All deaths reported* 1.2%

CABG(n=500)

Mortality

SoS

All deaths at 1 year

4.1%

2.5% 0.8%

PCI(n=488)

* As of presentation at ACC 2001; p value = 0.007

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 PCI5.8% for CABG

SoS

Mortality rate: ARTS

All deaths* 2.8%

CABG(n=605)

Mortality at 1 year

SoS

2.5%

PCI(n=600)

*p value = n/s

Serruys et al. N Engl J Med 2001; 344: 1117-24.

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

“I really do think that ultimately for bad multi-vessel 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 CaliffProfessor of Cardiology Associate Vice Chancellor for Clinical Research at Duke University

SoS

Plumbing

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 trialmortality 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

Percentage of patients suffering decline in cognitive function by >20% post-CABG compared to pre-CABG baseline

At 5 yearsAt discharge

Newman et al. N Engl J Med 2001; 344: 395-402.

53%

At 6 weeks

36% 24% 42%

At 6 months

SoS

Cognitive decline with CABG

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. SoS

“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 CaliffProfessor of Cardiology Associate Vice Chancellor for Clinical Research at Duke University

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 trade-unionism, which I hope we can get over.

Califf

SoS

“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 TopolProvost and Chief Academic Officer Chairman and Professor, Department of Cardiology Cleveland Clinic

SoS

Surgery or stenting, who decides?

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, well-presented, and just the kind of trial we need.”

SoS