EXCEL: Researchers accused of withholding key mortality data

Researchers on the EXCEL trial have been accused of withholding key mortality data when they first published results suggesting stents were as safe as open-heart surgery in treating patients with left main disease.

EXCEL, which was run by Gregg W. Stone, MD, the director of cardiovascular research and education at Columbia University Medical Center in New York, compared percutaneous coronary intervention (PCI) with Abbott’s Xience everolimus-eluting metallic stent to coronary artery bypass grafting (CABG) in patients with left main coronary artery disease. Stone and colleagues reported in the New England Journal of Medicine in December 2016 that PCI with the Xience stent was “noninferior” to CABG at three years, noting that people with Xience implants also experienced fewer adverse events 30 days after their procedures.

“A stenting procedure with Xience may be an acceptable way to increase blood flow to the heart for certain patients with left main coronary artery disease, taking into account a patient’s individual circumstances,” Charles A. Simonton, MD, CMO for Abbott’s vascular business, told Cardiovascular Business at the time the study was published. “This is important news for patients because in addition to improved safety, stenting procedures are much less invasive than open-heart surgery, potentially reducing recovery time and healthcare costs."

But BBC Newsnight reported Feb. 18 that EXCEL researchers were aware of longer-term mortality data at the time they published their results. The trial had launched in 2011 and continued to recruit patients over the next several years, so when Stone et al. first published their findings in 2016, they were aware of some mortality stats past three years. Still, they chose to publish only their three-year results.

“I’m absolutely appalled that they’ve done this,” Nick Freemantle, a biostatician at University College London, told the BBC. “I’ve taken a straw poll of my professional colleagues and it draws disbelief that people would do this.”

Stone’s team maintains they followed protocol in reporting their findings, but BBC Newsnight said that even the EXCEL safety committee was wary at the time.

“It might be very concerning if in the future, suspicions were raised that already available information on mortality was withheld from the cardiology and thoracic surgery community,” Lars Wallentin, head of the safety committee, reportedly wrote in an email to the researchers in 2017.

Data past three years suggested EXCEL patients implanted with stents were faring worse than their counterparts who’d undergone CABG. BBC Newsnight confirmed information that suggested more people fitted with stents were dying three years after their procedures.

Five-year data were eventually published by the team, appearing in NEJM in November 2019, but Stone and colleagues’ conclusion was the same: in patients with low- to intermediate-complexity left main disease, there was no significant difference between PCI and CABG in respect to death, stroke or MI.

According to the BBC, the researchers involved in EXCEL agreed to an independent review of the raw data.

EXCEL researchers responded to allegations last December, outlining in an 11-page statement their study protocol.

"Every important study raises new questions, and some of the findings will rightfully foster scientific debate," the team wrote. "Such deliberations are healthy, and we openly welcome this from all informed parties. To suggest, however, that hundreds of EXCEL investigators, including cardiologists, surgeons, statisticians and entire academic research organizations conspired to change definitions or withhold important study findings is offensive and without merit.

"Specifically, the surgical instigator of these concerns has now retracted several of his original grievances as being unfounded, whether his original statements were intentional mistruths or unintentional errors and exaggeration is not for us to speculate...Regardless of the motivations and actions of others, the EXCEL leadership will continue to exercise the highest scientific principles and ethics of our profession."