MUNICH, Germany — It was supposed to be a stunning victory for drug-eluting stents (DES).
Instead, the release of the SYNTAX study here during the annual congress of the European Society of Cardiology (ESC; Sophia Antipolis, France) has left some 24,000 participating cardiologists scratching their heads over the conclusions and sent the supporters of DES scrambling for damage control.
In the wake of the devastating reports in 2006 that DES was not superior to surgery, and perhaps even dangerous, interventionalists said they would meet criticisms head-on with SYNTAX, which stands for Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery.
Taxus is a global leader among drug-eluting stents and the manufacturer, Boston Scientific (Natick, Massachusetts) sponsored the SYNTAX trial.
Unfortunately for Boston Sci, SYNTAX concludes that the primary end-point of DES being non-inferior to coronary artery bypass graft (CABG) was not met.
In fairness, the study designers set the bar very high for DES, intending to deliver overwhelming evidence in favor of DES. The medical community agreed the final measure would be the rate of major adverse cardiac events (MACE) caused by percutaneous intervention (PCI) using DES during the 12 months following the procedure.
To meet the endpoint, PCI MACE needed to be not more than 5.5 percentage points greater than the rate of these adverse events experienced by CABG patients.
DES missed the mark by a mile against surgery (see related story "Results from SYNTAX trial").
Lead investigator Patrick Serruys, MD, of Erasmus University Medical Center (Rotterdam, the Netherlands), said he was "totally surprised" by the quality of surgeries, a comment echoed in a press conference by fellow DES supporters who said surgical techniques, such as off-pump procedures and perioperative care, had improved in recent years.
In clinical trials, MACE includes the number of patients who die and the number who experience a cerebrovascular accident (CVA) or a myocardial infarction (MI).
To close the door on criticisms of DES, the investigators in the SYNTAX study included in the MACE measure the number of times a patient had to return to the cardiologist for a repeat procedure called revascularization because the first intervention did not relieve the conditions.
This turned out to be the undoing of the DES supporters who had hoped SYNTAX would end the debate over the viability of DES procedures and create the opportunity to tell cardiologists that PCI is as good as surgery for their patients.
It was a tough break for DES defenders, as all other results except revascularization in the trial were quite good against CABG.
This means that DES is not dangerous for patients and, in fact, that it is indeed a viable alternative for cardiologists to recommend to their patients compared to CABG, which one cardiologist described as "a voluntary submission to willful bodily harm."
Not unexpectedly, Boston Scientific put a positive spin on the study findings.
"For PCI patients to do so well with such complex anatomy and advanced disease is extraordinary," said Keith Dawkins, MD, associate chief medical officer of Boston Scientific, in a company statement. "These patients, the majority of whom are normally treated with surgery, are the most challenging group ever studied in a DES clinical trial."
He also cited the SYNTAX trial's findings demonstrating a significant decrease in the rate of stroke for patients treated with PCI as compared to CABG.
"The significant difference in the stroke rate between the PCI and the CABG groups is an important finding," said Dawkins. "Physicians and their patients will now have the necessary information to weigh the risk of stroke associated with CABG versus the known higher rate of revascularization with PCI. We were also surprised to find that the rate of symptomatic graft occlusion in the CABG group was equivalent to the rate of stent thrombosis in the PCI group."
With more than 3,000 participants at the ESC Congress watching in the lecture hall and overflowing to the theater outside, where the presentation was broadcast, Christian Hamm from the Kerchhoff Heart Center (Bad Nauheim, Germany) took the stage to deliver the "Cardiologists' Perspective" of the findings.
"The conclusions of the study are difficult to understand, but the bottom line is that PCI failed to be shown as non-inferior," he said. "CABG is shown to be better and the hard end-point of reintervention is the issue."
Noting that cardiologists serve as the gatekeepers for patients entering the surgical arena, he shared suggestions for the take-home messages for fellow physicians so that they could describe these two options to patients.
The positive points for PCI are less chance of stroke, a shorter hospitalization and good-to-excellent repair of the damaged vessels.
For surgery there is less chance of returning for a second procedure and a more complete revascularization.
He noted that the results showed the incidence of thrombosis in stent patients, one of the sharp criticisms of DES in 2006 that shocked regulatory agencies are identical to the incidence of symptomatic graft occlusion occurring in CABG.
In the real world of discussing options with patients, however, he said the less-invasive nature of PCI is very attractive, with patients typically preferring to opt for the stent and risk the possibility of revascularization.
"None of our patients is going to say that if PCI is an option they want to do surgery first and then try the stent if that does not work," he said.
The SYNTAX study clearly shows that revascularization is the single issue limiting DES, he said. "Tell patients about their choices and say that if they want to see you again, choose PCI," he said.
The impact of the criticisms of DES starting at the EuroPCR congress for interventionalists in Barcelona in 2006, and the subsequent release of the Swedish SCAAR study, was a sudden drop in DES usage.
European usage dipped slightly, staying between 40% to 50% of PCI procedures, but sales of DES in the U.S. plummeted from over 90% usage in early 2006 to around 55% before the end of that year, where it has plateaued today, according to figures presented in a separate session here at the congress titled "Two Years After Barcelona."
Clinical trials come and go in prominence, but the results of the SYNTAX study are here to stay, likely with a significant lasting effect.
Not only did the cardiology community set the bar high with the MACE endpoint, they also agreed the study results would create a SYNTAX Score for the stratification of patients facing a revascularization.
In other words, once a patient returns to a cardiologist after a procedure complaining of recurring symptoms, or is hospitalized, the options for the subsequent surgery will be guided by the SYNTAX scoring.
The study team concluded that CABG remains the only treatment option for one-third of these patients.