CardioExchange Archive

CardioExchange welcomes David J. Cohen, Director of Cardiovascular Research at St. Luke’s Mid America Heart Institute in Kansas City, Missouri, to discuss the latest analysis from the SYNTAX randomized trial. The study has just been published in the New England Journal of Medicine, and Dr. Cohen is the lead author. Questions to Dr. Cohen come from CardioExchange’s Dr. Richard A. Lange and Dr. L. David Hillis.

In SYNTAX, 1800 patients with 3-vessel or left-main coronary artery disease (CAD) were randomized to undergo either coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) with a paclitaxel-eluting stent. The score on the angina-frequency subscale of the Seattle Angina Questionnaire (SAQ), the primary endpoint, increased significantly in both groups — but significantly more so in the CABG group. At both 6 and 12 months, the mean SAQ advantage of CABG over PCI was 1.7 points. Rates of freedom from angina were similar between the groups through 6 months, but a significant advantage in the CABG group emerged at 12 months (76.3%, vs. 71.6% with PCI). A maker of paclitaxel-eluting stents funded the trial.

Q: Your team characterized the advantage of CABG over drug-eluting stent PCI (1.7 points on the SAQ) as a “small” benefit in angina reduction. Given that the SAQ is not used in clinical practice, what should we consider a clinically meaningful benefit on that measure?

A: For an individual, a difference of 8 to 10 points on the SAQ angina-frequency score is the smallest amount that would be noticeable. It is difficult to define a “clinically meaningful” benefit for a population of patients. Nevertheless, we can fairly surmise that a mean difference of 1.7 points across the entire trial population suggests a clinically important angina benefit of CABG in only a small fraction of the participants.

Q: The PCI group had a significantly higher rate of repeat revascularization (13.5%, vs. 5.9% in the CABG group) and more often used antianginal medications. Might these differences have mitigated the benefits of CABG?

A: SYNTAX was a strategy trial, so it incorporated all aspects of the treatment strategy, such as an expected higher rate of repeat revascularization procedures to treat restenosis in the PCI group. It is likely that these additional procedures would have bolstered the overall effect of PCI. Similarly, increased use of certain antianginal medications in the PCI group might have mitigated the benefits of CABG. However, given that these are intrinsic components of the PCI strategy, it is not possible to isolate the magnitude of the individual effects with certainty.

Q: Among patients with a high SYNTAX score (a score that represented more-severe angiographically determined CAD), the PCI group had a higher rate of major adverse cardiac or cerebrovascular events than the CABG group. But the SYNTAX score did not predict the effect of treatment (CABG vs. PCI) on symptom relief. Did that surprise you?

A: It did, initially. However, at 1-year follow-up, the main effect of the SYNTAX score in the PCI group was an increased rate of repeat revascularization. Given that most of these events were additional PCI procedures, which are associated with rapid symptom relief and minimal morbidity, it is likely that any effect of restenosis in the PCI group was transient. Thus, by 12 months, we observed only a small difference in angina between the CABG- and PCI-treated patients.

Q: CABG is recommended over PCI in patients with high SYNTAX scores because of a higher rate of major adverse cardiac or cerebrovascular events with PCI. Your study showed that among patients with daily or weekly angina at baseline, the percentage of patients who were free of angina also was greater in the CABG group than in the PCI group at both 6 months (65% vs. 57%) and 12 months (70% vs. 60%). Should we therefore recommend CABG over PCI in patients with daily or weekly angina?

A: I believe that this is a reasonable interpretation of our data. However, even after being provided with this information, many patients may choose an initial PCI strategy to avoid the greater morbidity and more-prolonged recovery after CABG. In our study, the PCI group showed substantial benefits on a variety of measures of health status and quality of life at 1 month, and some patients may value those more-certain (but short-lived) benefits of PCI over the greater long-term angina relief afforded by CABG.

Q: Previous research has shown that patients (and physicians) have an inflated opinion of the benefits of coronary revascularization. How do we integrate the results of your study into clinical practice? 

A: Obviously, as a trial that directly compares two different forms of coronary revascularization with each other, SYNTAX does not elucidate the benefits of revascularization per se. Nonetheless, I believe that our results should reassure most patients with 3-vessel or left-main CAD that there are not major differences between a drug-eluting stent PCI strategy and a CABG strategy in terms of overall health status or symptom relief, beyond the initial 1- to 2-month recovery period. In clinical practice, this information (along with relevant data on expected longer-term clinical outcomes) should be explained to help each patient reach a decision that is appropriate for his or her lifestyle, values, and preferences.