Leaked data from the EXCEL trial suggest a cover-up of heart attack rates that would have put coronary stenting in a bad light, according to a BBC Newsnight report that is shaking up some clinical guidelines on left main revascularization.
“Newsnight has seen that unpublished data and it shows that under the universal definition, patients in the trial that had received stents had 80% more heart attacks than those who had open heart surgery,” according to the Newsnight article.
When the EXCEL trial was presented in 2016, 3-year results showed similar outcomes between percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) surgery among 1,905 patients who were at lower surgical risk and had left main disease.
Investigators had intended for periprocedural MI by the Third Universal Definition to be a secondary endpoint in the EXCEL protocol, Newsnight reported, but neither released this result to the public when the findings were first announced at the Transcatheter Cardiovascular Therapeutics meeting nor in the full report published in the New England Journal of Medicine.
What’s more, the Newsnight story described emails in which the EXCEL Data Safety Monitoring Board had raised concerns about the higher mortality rate observed in the PCI arm (8.2% vs 5.9%, P=0.11). It had been suggested that the investigators tried to bury this finding, according to a public accusation earlier this year by the surgeon David Taggart, MD, PhD, of the University of Oxford, England.
Taggart said he ultimately resigned from the EXCEL team because he disagreed with the authors’ conclusion that there is no significant difference between stenting and CABG in left main disease.
A Shifting in Stance for Medical Societies?
Now, in response to the latest revelations, the European Association for Cardiothoracic Surgery (EACTS) leadership is withdrawing its support for the 2018 European guideline on left main disease — drafted alongside the European Society of Cardiology (ESC) — that gives a class Ia indication for PCI in people with a low SYNTAX score.
“It is a matter of serious concern to us that some results in the EXCEL trial appear to have been concealed and that some patients may therefore have received the wrong clinical advice,” said Domenico Pagano, MD, Secretary General of EACTS, in a statement.
“If the information on the trial is proven to be correct, the recommendation is unsafe. On behalf of the EACTS Council I have written to the ESC to invite them to work with us to develop a new joint section of the guidelines as a matter of urgency,” according to Pagano.
The ESC stands by the current recommendations, it announced. The Society for Cardiovascular Angiography and Interventions (SCAI) too announced that it supports coronary stenting for left main disease in certain patients.
However, the ESC acknowledged that changes may be coming, alluding to EXCEL: “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. We look forward to reviewing these data with our surgical colleagues…to assess their relevance to our current recommendations.”
Instead of defining MI by troponin thresholds, the EXCEL leadership opted for a modified SCAI definition based on creatine kinase-MB, as noted on ClinicalTrials.gov.
MI was but one component of the primary composite endpoint (all-cause death, stroke, or MI), which turned out being comparable between study groups at a median of 3 years (15.4% with PCI vs 14.7% with surgery, P=0.02 for noninferiority).
“The SCAI definition has been used in multiple clinical trials because it avoids the pitfall of tabulating MI events that are small enough to have little clinical impact. Instead, the SCAI definition permits assessment of MI events that are likely to be clinically relevant,” according to a statement by SCAI in response to the criticism of EXCEL.
Asked for comment, the American College of Cardiology did not provide a response in time for publication.
Is There a Path Forward?
Interventional cardiologist Marco Valgimigli, MD, PhD, of University Hospital Bern, Switzerland, said he personally prefers the SCAI definition over the Third Universal Definition of MI.
The mortality result is “a matter of concern,” but it’s important that guidelines base their recommendations on primary endpoints alone to ensure that they are based on reproducible, relevant data, he told MedPage Today.
“[W]e should never forget that this is a secondary endpoint, in a relatively small study, which was not powered for it,” he said in an email. “This may simply be a play of chance as we saw many times before in the setting of different studies.”
“The debate about periprocedural MI definitions long predates EXCEL and the bottom line is that we have no way of knowing which definitions are the right ones, so to speak, and which are biased against one procedure over another,” commented interventional cardiologist Robert Yeh, MD, of Harvard Medical School and Beth Israel Deaconess Medical Center in Boston, who noted that he does have relationships with the trial sponsor, Abbott.
“What’s clear to me is that a significant amount of trust has been eroded between subspecialties, particularly in Europe, and all of the stakeholders have some responsibility in that. This is starting to take on the personality of a classic turf war, which is unfortunate given all of the collaboration that has occurred between cardiac surgeons and cardiologists over the past decade,” Yeh told MedPage Today in an email.
Full transparency would be “an obvious path forward” for the EXCEL leadership, he said.
A statement is in the works from the group, said EXCEL lead investigator Gregg Stone, MD, of Icahn School of Medicine at Mount Sinai in New York City.
“I think the controversy that has erupted reflects poorly on all the parties involved,” Yeh said. “[T]his debate is really an academic one, a bit of ‘inside baseball,’ and it’s not clear why this had to spill out into the public sphere with so much sensationalism.”
Valgimigli disclosed acting as co-principal investigator on an Abbott trial and consulting for the company.
Yeh reported receiving investigator-initiated research grants and serving on scientific advisory boards and/or consulting for Abbott Vascular, Boston Scientific, and Medtronic.
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Source: MedicalNewsToday.com
