The SYNTAX Trial
October 2008
This monthly column in Cath Lab Digest reviews important points of distinction in drug-eluting stents, from characteristics to techniques, to provide valuable and relevant information about this technology.
Dr. Feldman currently practices at Evanston Hospital, where he is director of the cardiac catheterization laboratory and holds the Walgreen Chair in interventional cardiology. He received his undergraduate and medical training at Indiana University, completing residency training as Chief Resident at Rush-Presbyterian-St. Luke’s Medical Center in Chicago, Illinois. After finishing his Cardiology Fellowship at the University of Chicago, he remained there as Professor of Medicine and Director of the Cardiac Catheterization Laboratory until moving to Evanston. Dr. Feldman has authored over 300 manuscripts, chapters, abstracts and editorials. He is a Percutaneous Coronary Intervention Guideline co-author and is on the American Board of Internal Medicine Interventional Cardiology test writing committee. Dr. Feldman is a past-president of the Society for Cardiovascular Angiography and Interventions, and recently chaired the Annual Scientific Sessions of the Society, as well as the American College of Cardiology i2 Interventional Summit. He participates in numerous clinical investigations, with major research interests that include non-surgical, percutaneous repair of the mitral valve, catheter-based aortic valve replacement, shunt closure for congenital heart disease and also for migraine headache, left atrial appendage closure, carotid stent implantation and development of new coronary stents.
How is the SYNTAX trial different from past trials comparing percutaneous intervention (PCI) and coronary artery bypass graft (CABG) surgery?
There is a long history of large, randomized trials, such as the Bypass Angioplasty Revascularization Investigation trial and the Emory Angioplasty vs. Surgery Trial, comparing plain balloon angioplasty to CABG. Additionally, a variety of trials of different sizes — some randomized and some not — have looked at bare-metal stents (BMS) and then ultimately drug-eluting stents (DES) versus surgery. The SYNTAX trial is unique because it is a randomized trial comparing DES, specifically the TAXUS® Express2™ stent, with bypass surgery for left-main disease and three-vessel disease. While prior randomized trials have used strict inclusion and exclusion criteria and thus enrolled Stents are not labeled for use in the treatment of left-main disease and three-vessel disease. What is the typical approach to treating these patients?
In the United States, treatment for left-main disease is fundamentally surgical, although there are some higher-risk patients being treated with PCI. Target vessel revascularization (TVR), which is more frequent with PCI, and uncertainty about mortality after PCI, have been the major factors resulting in the predominantly surgical treatment of left-main disease and three-vessel disease. Current AHA/ACC/SCAI guidelines for the treatment of left-main disease recommend PCI only for patients who are not good candidates for CABG. In my experience, I see left-main stenting being used more and more in such difficult cases.
What SYNTAX trial data were presented at the European Society of Cardiology (ESC) meeting in September, and what data are being presented in October at the Transcatheter Cardiovascular Therapeutics (TCT) meeting? What will be of particular interest to interventional cardiologists?
The data presented at ESC reported the overall results from the SYNTAX trial, the major endpoints for entire randomized patient groups. Additionally, key data will be presented at the TCT meeting, where investigators will present data from the left-main subgroup, three-vessel subgroup and the nonrandomized patient registry. The biggest point of interest for interventional cardiologists is whether there is a difference in mortality rates between PCI and CABG patients.
Historically, nonrandomized comparisons of left-main surgery and PCI have been consistent with outcomes in other subgroups of coronary disease, that is, they have demonstrated similar rates of death and myocardial infarction (MI) to CABG at one year, with an increase in revascularization.
The same holds true for the SYNTAX trial data presented at ESC. The main results of the trial show no difference in the combined safety endpoint for PCI and CABG (death, MI and stroke; 7.7% for CABG and 7.6% for PCI) at one year. The difference in repeat revascularizations for the overall cohort was 100 mm of stented length.
Early in the DES era, our best hope was that this technology was going to level the playing field between surgery and PCI; however, over the past years, there have also been advances in bypass surgery as well. The quality of the surgery demonstrated in the SYNTAX trial was also impressive, with 97% of patients studied getting at least one arterial graft and 27.6% having double internal mammary artery grafts. Interestingly, clinically defined stent thrombosis and graft occlusion were nearly identical between PCI and CABG patients (3.3% and 3.4%, respectively). Another important difference between PCI and CABG was a higher stroke rate in the surgery group (0.6% for PCI vs. 2.2% for bypass; p = 0.003).
Based on current industry patient trends and data, would you consider the patients enrolled in the SYNTAX trial to be traditional patients treated with PCI today?
Overall, the patients recruited in the SYNTAX trial are a unique study group in the PCI field with very complex anatomy and advanced disease. The intention of the SYNTAX trial was to include all-comers in the left-main and three-vessel disease groups so that patients who were considered suitable by both surgeons and interventional cardiologists were randomized. If the surgeon thought a patient was a poor CABG candidate, or if the cardiologist thought that the extent of disease or lesion morphology was not acceptable for PCI, the patient would not be included in the randomization process. Patients with chronic total occlusions were not excluded, and > 70% of patients in the study had bifurcation lesions.
How would you summarize the results presented at ESC?
The prespecified primary endpoint is noninferiority, using the combined endpoint of death, stroke, MI and repeat revascularization (MACCE). The rate of repeat revascularization in the PCI group was 7.8% higher than CABG, driving the increase in total MACCE of 5.7% for PCI at 12 months. This exceeded the prespecified noninferiority boundary for the combined primary endpoint.
What are the key take-away points from the SYNTAX trial?
We have a decades-long history of trials comparing PCI and CABG, from the balloon angioplasty era, through BMS, and now with the SYNTAX trial, in DES. Historically, death and MI have been similar in all of these trials, and PCI has had an increased rate of repeat revascularization compared to CABG. Safety in terms of death, MI and stroke remained the same for PCI and CABG in the SYNTAX trial. The increase in repeat revascularization for PCI compared to CABG was lower than in any prior trials, despite a much more complex coronary anatomy of patients studied.
How could the SYNTAX trial impact the medical community and your interventional cardiology practice?
The SYNTAX trial has the potential to change the balance between surgery and PCI in patients with left-main and three-vessel disease. For the left-main disease group, we might see the borderline between PCI and CABG shift more towards “better” or even “good” surgical candidates being considered for PCI. It remains to be seen whether this applies to all-comers or just certain subgroups of the left-main population (e.g., patients with ostial lesions). For the three-vessel disease group, a high likelihood of success may no longer be required in all three vessels. Patient and lesion complexity are being quantified in this trial. We used the logistic Euroscore to quantify patient risk. We also used a new, unique lesion scoring system to assess coronary disease burden and complexity, the SYNTAX trial score. We will be able to stratify outcomes utilizing these measures. The SYNTAX trial will finally give us the randomized data needed to help guide decision-making in the treatment of these complex patients.
Sponsored and prepared by Boston Scientific Corporation.
