Medical Device Daily Contributing Writer

ORLANDO — With a massive number of clinical trial data being reported here the past few days, winnowing out the most important ones became a major challenge. However, one trial that stood out from the crowd because of its focus on quality of life (QOL) and healthcare cost outcomes was the Synergy between PCI with Taxus and Cardiac Surgery (SYNTAX) trial.

The clinical findings of SYNTAX were originally presented at the 2008 annual meeting of the European Society of Cardiology (Sophia Antipolis, France) in September 2008 and then were fully discussed in the March 5, 2009 issue of the New England Journal of Medicine in an article titled "Percutaneous Coronary Intervention versus Coronary-Artery Bypass Grafting for Severe Coronary Artery Disease."

The authors of the article, which included some of the world's most prestigious cardiac surgeons and interventional cardiologists, concluded that "coronary artery bypass grafting (CABG) remains the standard of care for patients with three-vessel or left main coronary artery disease ... compared with percutaneous coronary intervention (PCI)."

CABG surgery was favored because it resulted in fewer complications, as measured by a combination of death, heart attack, stroke and recurrent angina requiring treatment. The incidence of these complications, officially termed Major Adverse Cardiovascular and Cerebrovascular Events (MACCE) was almost 50% higher at one year in the PCI cohort as compared to the CABG cohort (17.8 % vs.12.1%).

As expected, cardiac surgery organizations like the Society of Thoracic Surgeons (Chicago) hailed this study, saying that "the SYNTAX trial ... demonstrates that CABG surgery provides markedly better results within the first year, and many experts expect this relative advantage to increase over time. In summary, for patients with severe coronary artery disease, CABG surgery is the right thing to do."

The SYNTAX trial was funded by a research grant from Taxus drug-eluting stent (DES) manufacturer Boston Scientific (Natick, Massachusetts) and had a second, important aspect which delved into quality of life and healthcare economics issues of these two revascularization modalities. This data was presented here on Saturday at a "Late Breaking Clinical Trials" session.

The principal objectives of this aspect of the trial, whose findings were presented by David Cohen, MD, director of cardiovascular research of the Saint Luke's Mid America Heart Institute (Kansas City, Missouri) was twofold: First, to compare health-related QOL outcomes for patients with left main and three-vessel coronary artery disease, treated with either PCI with the Taxus stent or with bypass surgery and second, to compare short- and long-term medical care costs according to the two treatment strategies.

Patients were divided into three groups low, moderate and high based on their SYNTAX score or risk profile. A detailed analysis of the costs and quality-of-life outcomes suggested that CABG-treated patients have more angina relief at one year than those treated with PCI but that PCI is a more cost-effective strategy.

As can be clearly seen in Table 1, PCI enjoyed a cost advantage in all three risk categories but its most significant cost advantage occurred in the low risk patient group and diminished substantially as the patient's condition worsened.

As might be expected, the QOL of PCI patients during the first month post-procedure was much better, reflecting the far more invasive nature of CABG. As time went on, however, these differences evaporated. In higher-risk patients, CABG was the clear winner when both costs and lifestyle issues are considered.

According to Cohen, information from this trial may be helpful as physicians, patients and payors weigh the advantages and disadvantages of DES vs. CABG in treating complex coronary artery disease.

"There is no single answer to the cost-effectiveness question for this population. These are all very complex patients, but in the least complex of them with the lowest SYNTAX score ... PCI provides a better overall quality of life and substantially lower cost," Cohen said.

He further elaborated saying that "for the highest risk patients ... the story is completely flipped we have actually better quality-adjusted life expectancy for the bypass-surgery patients and neutral cost, meaning that bypass surgery, even at this very admittedly early time point, appears to be the clear winner in that group."

Press conference moderator Ralph Brindis, MD, clinical professor of medicine at the University of California San Francisco and the regional senior advisor for cardiovascular diseases for northern California of Kaiser Permanente (Oakland, California) noted that this trial provides "huge information for physicians and their patients and will help them make a more informed decision about managing their disease."

There are limitations to this study, which were clearly pointed out. The cost estimates were done on the basis of U.S. prices and therefore may not apply in Europe and Canada. In those areas, the upfront costs may be lower, particularly for drug eluting stents.

Second, this trial followed patients for only one year and the cost outcomes and QOL measures would likely change as time goes on. For example, repeat PCI revascularizations will likely increase costs in the DES-treated group, but the price of anti-platelet therapy a significant cost in DES-treated patients will most likely decline substantially when widely-used post PCI anti-platelet agent Plavix (clopidogrel) loses its patent protection in the U.S. in late 2011.

In a commentary after the data was presented, Mark Hlatky, MD, of the Stanford University School of Medicine (Stanford, California) also emphasized the need for longer-term data, admitting he was "a little uncertain as to the long-term cost-effectiveness at this point."

Hlatky also called the data "very important," but noted that there are clear limitations of one-year follow-up.

"We have not yet seen the full costs and long-term differences and effectiveness may differ, so we will need to do further follow-up. But, overall, this is generally consistent with some of the things we've seen."