Surgery Is Best for Most Patients, Final SYNTAX Data Confirm

November 01, 2012

BARCELONA — Final, five-year results from the SYNTAX trial comparing CABG surgery and PCI with a drug-eluting stent (DES) in patients with complex coronary disease confirm the message that started to emerge from this study after just a couple of years: the majority fare better after surgery.

But one interesting finding has been confirmed in subgroup analyses. While high- and intermediate-risk patients with three-vessel disease will do better after surgery, and those at low risk with three-vessel disease fare equally well with either strategy, albeit with a higher rate of revascularization if they opt for PCI, the same is not true for those with left main disease. In this instance, "the lower- and intermediate-risk groups seem to do as well with PCI as with CABG, if not better," surgeon Dr David Taggart (University of Oxford, UK) told heartwire . "This needs more investigation; it may just reflect left main as a slightly different type of disease; it may mean that these patients also have more carotid disease." More light should be shed on this from the ongoing EXCEL trial, he observes, which is comparing around 2500 patients with left main disease randomized to bypass surgery or PCI with the Xience stent (Abbott) and followed for at least three years.

"The SYNTAX findings are the most important results ever of any trial of stenting vs CABG in the whole history of intervention, by a mile, because for the first time ever this reflected real patients, whereas the previous 19 trials were all in extremely highly selected patients and had little relevance to real clinical practice," Taggart notes.

The five-year SYNTAX results have been presented in various guises over the past 10 days; first at TCT 2012 and then here at the European Association for Cardio-Thoracic Surgery (EACTS) 2012 Annual Meeting. Taggart was a discussant for presentations at both meetings.

But Are SYNTAX Results Relevant Today?

Taggart stresses that the results of SYNTAX remain very relevant to today's clinical practice, despite some saying the findings might have been different if newer-generation DES had been employed, rather than the first-generation Taxus stent (Boston Scientific) that was used in this study. This is because it ultimately comes down to the differences between surgery and stenting procedures and the resultant effects on the cardiac anatomy, he explains.

 
The SYNTAX findings are the most important results ever of any trial of stenting vs CABG in the whole history of intervention.
 

"A lot of the interventional cardiology community fails to understand the difference between the two techniques," he says. "With surgery, you put the bypass graft to the mid-coronary vessel, so you protect the whole of the distal myocardium. Whatever type of stent you use, if you get more disease either immediately proximal or immediately distal to the stent--because many of these patients develop new disease--then the effect for a stent is nullified, and that's the major benefit of surgery. That's why it doesn't matter what type of stent you use; you do not offer the protection to the myocardium.

"How do we know that? If we look at SYNTAX, even apart from the mortality benefit of CABG, the incidence of myocardial infarction out to five years is two to three times lower with CABG, and that's because of the effect I just described. It doesn't matter what type of stent you use, you will not offer that benefit. If we had repeated SYNTAX with a second- or third-generation DES, you would still see the benefits of CABG."

 
If we had repeated SYNTAX with a second- or third-generation DES, you would still see the benefits of CABG.
 

Further light will be shed on this issue next week , at the American Heart Association 2012 Scientific Sessions, when the much-anticipated main results from the Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multivessel Disease (FREEDOM) trial, comparing PCI with CABG in patients with diabetes, are presented. The mortality/clinical benefit of surgery was even greater for diabetics than for the population as a whole in SYNTAX, Taggart said, but because the number of diabetic patients was small, they were not able to subdivide them into SYNTAX subgroups, he noted.

Taggart also notes that bypass surgery hasn't stood still since SYNTAX began. "If you look at the whole of the UK last year, the mortality for elective CABG was 0.8%, and for most of these patients there is an excellent long-term outcome."

"Sobering" Message: 80% of Patients With Three-Vessel Disease Fare Best With Surgery

SYNTAX was an 1800-patient trial conducted in Europe and the US, randomizing patients with complex disease to either CABG or PCI using the Taxus DES. The one-year results showed that PCI did not meet the prespecified margin of noninferiority, although the composite safety end point of death/cerebrovascular events/MI rates was almost identical between the two groups. The stroke rate, by contrast, was higher in the CABG-treated patients. By two years, the event rates continued to diverge, with CABG cementing its status as the preferred strategy, and there was also a new signal of increased MI among PCI-treated patients.

The three-year results confirmed that "intermediate-risk" patients with complex coronary disease by SYNTAX score are probably better off getting open-heart surgery than PCI, and at four years, the data showed--for the first time--a divergence in death rates: all-cause mortality and cardiac death were both significantly higher in the PCI group compared with the surgery arm. At this point, the excess rate of strokes initially observed in the CABG arm had also leveled out.

When the five-year data were analyzed for those with three-vessel disease only, the same pattern emerged: a significantly higher rate of revascularization and major adverse cardiac and cerebrovascular events (MACCE) in the PCI group and better safety outcomes in the surgery group. However, the results are notably affected by baseline lesion complexity.

 
The results give a very sobering message . . . that almost 80% of patients with three-vessel disease have a strong . . . survival advantage [with CABG] at five years.
 

The results "give a very sobering message to the interventional community, that almost 80% of patients with three-vessel disease have a strong, 79% survival advantage [with CABG] at five years, and that's a pretty powerful take-home message," says Taggart.

Only those at low risk (SYNTAX score of <22), which represent the remaining 20% of patients, "seem to do equally well with PCI, albeit with a higher rate of repeat revascularization," he observes.

Taggart adds also that the five-year results of SYNTAX "underestimate the real benefit of surgery still, because when you look at the survival curves, especially for three-vessel disease, they are diverging sharply at five years, which suggests that with further follow-up, the benefits are going to be even greater."

SYNTAX Five-Year Results for Patients With Three-Vessel Disease

Outcome CABG, n=549 (%) PCI, n=546 (%) p
Primary end point: MACCE 24.2 37.5 <0.001
All-cause death 9.2 14.6 0.006
Cardiac death 4.0 9.2 <0.001
MI 3.3 10.6 <0.001
Cerebrovascular accident 3.4 3.0 0.66
Repeat revascularization 12.6 25.4 <0.001
Safety end point: All-cause death/cerebrovascular accident/MI 14.0 22.0 <0.001

But for left main disease, advice is slightly different

The five-year SYNTAX results can be interpreted slightly differently for patients with left main disease, investigators said. Revascularization with PCI has comparable safety and efficacy outcomes to CABG and is therefore "a reasonable treatment alternative in this patient population, in particular when the SYNTAX score is low (<22) or intermediate (23–32)."

Further breakdown showed PCI outcomes were "excellent" relative to CABG in those with left main isolated (n=91) and left main plus one-vessel disease (n=138), with no significant differences in MACCE between those who underwent CABG surgery and those who received PCI. The same was true for those with left main plus two-vessel disease (n=218).

But for those with left main and three-vessel disease (n=258), the pendulum once again swings in favor of surgery: MACCE occurred in 29.9% of these patients who underwent CABG surgery vs 44.0% who received PCI (p=0.04).

SYNTAX five-year results for patients with left main disease

Outcome CABG, n=348 (%) PCI, n=357 (%) p
Primary end point: MACCE 31.0 36.9 0.12
All-cause death 14.6 12.8 0.53
Cardiac death 7.2 8.6 0.46
MI 4.8 8.2 0.10
Cerebrovascular accident 4.3 1.5 0.03
Repeat revascularization 15.5 26.7 <0.001
Safety end point: All-cause death/cerebrovascular accident/MI 20.8 19.0 0.57

 

The SYNTAX researchers said that guidelines from the European Society of Cardiology in 2010 and a "focused guidelines update" from the American Heart Association/American College of Cardiology in 2009 state that PCI in the left main, previously not recommended, should be considered an alternative to surgery in patients at low risk for procedural complications.

Taggart is an investigator in the EXCEL trial and has no financial conflicts of interest.

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