EACTS Calls for Independent Left Main CAD Evidence Review, Urges ESC Input

The European Association for Cardio-Thoracic Surgery (EACTS) released a new statement Thursday summarizing its reasons for withdrawing support for the “left main chapter” of the joint European Society of Cardiology (ESC)/EACTS myocardial revascularization guidelines. The “unprecedented” move, writes Domenico Pagano, MD (University Hospitals/Queen Elizabeth Hospital, Birmingham, England), on behalf of the EACTS Council, was unanimous and was taken with “considerable care.”

Pagano, the EACTS secretary general, details the actions the Council is taking, among them an independent statistical review of the data—including the EXCEL results—that underpin the current recommendations.

As reported by TCTMD, EACTS earlier announced they were withdrawing support for the left main recommendations just prior to the airing of a BBC Newsnight broadcast alleging that critical data were concealed in the public reporting of the EXCEL trial. The investigative piece prompted a 3,500-word response from EXCEL investigators, triggering a rebuttal from David Taggart, MD, PhD (University of Oxford, England), the surgeon who first raised concerns about the trial at the 2019 EACTS meeting in October.

A divisive and increasingly bitter debate has broken out in the wake of the BBC report, most notably on Twitter, with some calling for the published trial results to be retracted. The New England Journal of Medicine, which published both the 3-year and 5-year EXCEL results, has said the concerns do not meet its criteria for retraction.

According to Pagano’s December 19, 2019, statement, three decisions were adopted at a December 7 meeting of the EACTS Council. These included unanimous agreement to withdraw support for the left main coronary artery disease (LMCAD) section of the guidelines, to publicize that decision widely, and to “immediately” invite the ESC “to participate in a new joint task force to review the LMCAD recommendations in the guidelines.”

BBC Insights and Evidence Review

The EACTS document also offers new information on the association’s interaction with the BBC, saying that Newsnight journalists approached Nick Freemantle, PhD (University College London, England), to review information leaked to BBC journalists. Freemantle then shared those data and his analysis with the EACTS Council which, they say, were viewed alongside “several matters of scientific and professional propriety.”

Also in the new statement is a summary of the evidence originally used to develop the left main recommendations in the 2018 guidance. It then goes on to detail the reasons why “the evidence available has changed.” Here, Pagano cites two reasons for the EACTS pivot. The first is the organization’s “more complete understanding” of the 3-year EXCEL data using the as-yet unpublished MI definitions that “has reversed the perceived advantage/noninferiority of PCI compared with CABG for LMCAD disease.” These were purportedly shared with the BBC but have not been publicly released.

For their part, the EXCEL investigators have said that reporting procedural MI rates according to the Universal Definition was “not possible,” since collection of troponins was optional in EXCEL. Taggart has disputed this explanation, arguing that CK-MB measurements could have been used instead and that these must have been what was leaked to the BBC.

The second reason for the EACTS withdrawal, writes Pagano, is that the 5-year data show a significant mortality advantage for CABG over PCI.

“The guidelines for myocardial revascularization must be reviewed urgently,” Pagano concludes. “By working together collaboratively and transparently, we can restore confidence in our clinical recommendations and send a strong signal to the public that patients’ interests are at the center of all we do and say.”

What Happens Next

In terms of next steps, the EACTS notes that in addition to contacting the ESC to jointly consider the evidence, it is proposing that the guideline committee adhere to the “gold standard” set out by the Institute of Medicine for trustworthy guideline development. Pagano also notes that they have invited Holger Jens Schünemann, MD, PhD (DeGroote Cochrane Canada Centre at McMaster University, Hamilton, Canada), to oversee the guideline review.

Of note, both Schünemann and Freemantle participated in the explosive EACTS conference session that first set off the current controversy.

As for the ESC, they issued a position statement on December 11, 2019, saying that it stands by the current recommendations based on the evidence available at the time of the guideline review. “In the past few days, we have been informed that there may be additional findings from one study that had not been included in the original publication or shared with the ESC or its guidelines Task Force,” the ESC statement reads. “We look forward to reviewing these data with our surgical colleagues, also in the context of further evidence published in 2019, and to assess their relevance to our current recommendations.”

Earlier this week, TCTMD reported on Taggart’s rebuttal to the EXCEL response and incorrectly characterized Taggart’s position as calling for EXCEL to be retracted, later issuing a correction. Asked by TCTMD to clarify his position, Taggart emailed a link to the new EACTS statement, saying his view “is the same as that of the EACTS.”

“Until the full data is published we have to be very cautious in recommending PCI in these relatively young patients with low/moderate disease,” Taggart’s email continued. “There is now so much controversy on what data was actually available (but not presented, despite being mandated in the protocol) and the timing of the alerts of the [data and safety monitoring board] that, in my opinion, the data should be reanalyzed by a group of clinician scientists and statisticians who are completely independent of the trial. This would go a long way to dispelling the concerns that have been repeatedly raised by many voices and provide enormous reassurance to doctors and our patients in ensuring that we are actually making the best evidence-based recommendations for treatment. Depending on the results of such an analysis, that would then allow the NEJM the opportunity to decide if they wish to continue to support the publication.”

When EXCEL researchers issued their response to this controversy last week, co-principal investigator Gregg Stone, MD (Icahn School of Medicine at Mount Sinai, New York, NY), said they would not be responding to further media requests.

Note: Stone is Co-Director of Medical Research and Education at the Cardiovascular Research Foundation, the publisher of TCTMD.