The New England Journal of Medicine (NEJM) has launched a review into the data from the EXCEL trial, two members of the BBC Newsnight team have reported in the BMJ. Deborah Cohen and Ed Brown from the Newsnight current affairs programme say that it is not clear how long the review process will take.
The move follows months of controversy about the trial’s findings, following the broadcast of investigations by BBC Newsnight that cast doubt upon the validity of the trial’s findings.
Writing in the BMJ, Cohen and Brown describe the definition of MI specified in the EXCEL protocol as “unusual”. They add: “At three years, no difference was found between the two procedures in rates of myocardial infarction using the investigators’ preferred definition (0.93, 95% confidence interval [CI] 0.67–1.28; p=0.64). However, data from the trial leaked to BBC Newsnight showed that, when the universal definition was used, there was an 80% increased risk of myocardial infarction with PCI (hazard ratio 1.79, 95% CI 1.25–2.57, p=0.002).”
As reported in Cardiovascular News last month, the Society for Cardio-Thoracic Surgery in Great Britain and Ireland (SCTS) and the American Association of Thoracic Surgery (AATS) wrote a joint letter to the NEJM expressing concerns over the conduct of the trial and its conclusions, in particular that the inferior survival for patients treated with stenting in EXCEL did not receive sufficient emphasis. Both societies also raised the issue of potential conflicts of interest generated by industry-sponsored trials and how these should be recognised and mitigated by triallists, reviewers, and editors.
EXCEL was an international, open-label, multicentre, randomised trial that compared percutaneous coronary intervention (PCI) using an everolimus-eluting stent (Xience, Abbott) and coronary artery bypass grafting (CABG) for the composite endpoint of death, myocardial infarction (MI), and stroke in patients with left main disease. It concluded there was no significant difference between the procedures. The five-year findings were presented at the Transcatheter Cardiovascular Therapeutics scientific symposium (TCT 2019; 25–29 September, San Francisco, USA) and published in the NEJM.
But in December 2019, Newsnight alleged that unpublished data from EXCEL, based on the universal definition of myocardial infarction, indicated that “80% more patients had a heart attack” in the PCI group than in the CABG group. This was disputed by lead investigator Gregg W Stone (Icahn School of Medicine at Mount Sinai, New York, USA) and the other EXCEL investigators, but led to the European Association of Cardio-Thoracic Surgeons (EACTS) withdrawing its support for the left main section of its joint guidelines with the European Society of Cardiology (ESC) on myocardial revascularisation.
Last month, a second Newsnight programme claimed that investigators “held back” data from the published results of the trial. Cohen said that Stone and colleagues could have published mortality data in 2016 that showed that “more people had died” with stents.
As the debate has rumbled on, many societies have released statements on the controversy. The Society for Thoracic Surgeons (STS) called for an independent analysis, while the Cardiovascular Research Foundation (CRF) announced that it had commissioned an independent review of the data. The American Association for Thoracic Surgery (AATS) suggested that all of the EXCEL data should be “made publicly available for analysis and interpretation”. EACTS also reached out to EXCEL investigators to “offer assistance” in resolving concerns raised about data from the trial. Both the British Cardiovascular Intervention Society (BCIS) and the Society for Cardiovascular Angiography (SCAI) have previously indicated that they continue to endorse the existing guidelines.
A spokesperson for the NEJM confirmed to Cardiovascular News: “A review process is under way regarding the study and the published findings.” No further details about the process were provided.
Cardiovascular News has also approached Newsnight and Gregg Stone for comment, and will update this story accordingly.