Medical Device Daily Associate
PARIS – In recent years, the outcomes and risks of both coronary artery bypass graft (CABG) surgery and less-invasive percutaneous coronary intervention (PCI) treatments have been substantially improved through new treatment strategies, patient monitoring and enhanced technologies such as drug-eluting stents (DES).
However, studies comparing CABG and PCI using bare-metal or drug-eluting stents have been limited to highly selected patient populations. For the most severe forms of coronary artery disease involving all three coronary arteries, the left main artery, or both, the optimal treatment strategy remains undetermined.
Boston Scientific (Natick, Massachusetts), which is sponsoring the SYNTAX clinical trial, said at the EuroPCR 2005 meeting in the Palais de Congr s that the study will compare the performance of drug-eluting stents with cardiac surgery in the most complex patient subsets: those with coronary artery disease in all three coronary arteries, in the left main coronary artery, or both.
This randomized, controlled clinical trial is designed to compare 12-month outcomes of PCI using the Taxus Express2 paclitaxel-eluting coronary stent system with CABG surgical treatment. A multi-center, prospective trial, SYNTAX will involve more than 4,300 patients at up to 90 sites in Europe and the U.S.
Discussion of the trial came on the heels of research released Wednesday by the New England Journal of Medicine indicating that angioplasty/stent procedures aren’t as effective as CABG for the sickest patients.
That research involved the review of two government databases in New York State covering nearly 60,000 heart disease patients, and included findings that those patients with three blocked arteries who received stents were 1.56 times as likely to die within a three-year period as were those who underwent CABG procedures. Those with two blocked arteries who underwent angioplasty and stent placement rather than coronary bypass were 1.33 times as likely to die.
However, the SYNTAX trial will mark the first evidence-based study measuring results with the competing procedures. Its principal investigators are Friedrich Mohr, MD, program director of the heart center/cardiothoracic surgery at the University of Leipzig (Leipzig, Germany), and Patrick Serruys, MD, PhD, chief of interventional cardiology at the Thoraxcenter at Erasmus University (Rotterdam, the Netherlands).
The trial is likely to provide cardiac surgeons such as Gianni Angelini, MD, of the Bristol Heart Institute at Bristol Royal Infirmary (Bristol, UK), with the first true head-to-head results that they have been clamoring for (Medical Device Daily, May 25, 2005).
Speaking during a conference session, Serruys expressed confidence that current PCI techniques should continue to reduce the need for coronary surgery. Indeed, he reminded his audience of his “rosy prophecy,” stated at the 2000 European Society of Cardiology (Sophia Antipolis, France) meeting, that the results of DES would surpass those of CABG for the treatment of multi-vessel coronary disease.
He cited Johnson & Johnson’s (New Brunswick, New Jersey) ARTS II Registry results, which aimed to study the results of stenting in patients with similar characteristics to the 1,205 who were randomized to either CABG or bare-metal stents in the original ARTS I trial. A total of 607 patients with two- and three-vessel coronary disease (VD) were recruited and followed for one year.
The “rosy prophecy” was indeed fulfilled, with 89.2% of DES patients found free of major adverse cardiac events at one year, compared with 88.4% for ARTS I CABG and only 73.5% for ARTS I PCI with the bare-metal stent.
That being said, he did acknowledge that there is one major problem with interpretation of the data from most of the randomized trials comparing the two approaches: only a very small portion of real-world patients are included.
As an example, he cited the results of the ARTS I trial, which compared the company’s bare-metal stents to CABG.
In ARTS I, he said that 76% of patients did not meet the clinical entry/exclusion criteria, the interventional cardiologist and cardiothoracic surgeon could not agree that the patient was randomizable in 18%, and 2% of patients would not agree to participate. This left only 4% of the total patient pool that was randomized.
“And that’s where the surgeons tell us that this is a joke, ‘You are not treating the patients that we are treating,’” Serruys said.
It is for that reason that the SYNTAX trial was designed, he said, “as a new breed,” designed “to take on all comers,” meaning all patients will be enrolled.
Based on an initial assessment, the treating cardiothoracic surgeon and interventional cardiologist will jointly decide whether a patient meets the eligibility requirements for both treatment approaches (CABG and PCI).
Patients who are eligible for both treatment options will be enrolled in the randomized arm comparing CABG to PCI, which will include about 1,500 patients. Patients determined to be eligible for only one treatment option will be enrolled in one of two “nested” registries tracking either CABG or PCI, which will include about 2,750 patients combined.
Results from the randomized arm will help compare CABG to PCI in treating patients eligible for both treatment options. The nested registries will define profiles of patients eligible for only one of the treatment options. The recruitment will be non-competitive.
Based on the run-in phase data, each center will be required to enroll a minimum of 16 and a maximum of 32 patients in the randomized PCI/CABG cohort. Sites will continue enrollment into all three groups until they have reached the allocated number of randomized patients or until total enrollment of 1,500 patients in the randomized cohort is complete. Randomized patients will be stratified at each site based on the presence or absence of left main (LM) disease and medically treated diabetes mellitus.
The primary objective of the randomized cohort of the trial is to compare the major adverse cardiac and cerebrovascular events (MACCE) rate through 12 months post-allocation between patients treated with Taxus Express2 paclitaxel-eluting SR stents and patients undergoing CABG for de novo three-vessel or LM disease (isolated or in conjunction with 1, 2 or 3VD). The primary endpoint is the 12-month major adverse cardiac and cerebral event (MACCE) rate, which includes all cause death, stroke, myocardial infarction and repeat revascularization.
Additionally, a new scoring system, the SYNTAX score, is being developed to prospectively characterize the coronary vasculature with respect to lesion frequency, location and complexities.
“If SYNTAX with three vessel disease and left main [disease] . . . show[s] non-inferiority then this population will become eligible for PCI in the future in all practice and we will have guidelines,” Serruys said. If, however, SYNTAX fails to show non-inferiority then he said that CABG “will remain the gold standard for treatment of these patients.”
The SYNTAX trial received conditional FDA approval on Oct. 22, 2004, and enrollment began at Institut Hospitalier Jacques Cartier (Massy, France) on April 5. The FDA allowed an initial enrollment of 600 patients across 40 sites. Final enrollment is contingent upon FDA review of 30-day safety data on the first 200 randomized patients.