The European Association of Cardio-Thoracic Surgeons (EACTS) has published a detailed account of the process that led to its “unprecedented” decision to reverse its endorsement of a section of its joint 2018 myocardial revascularisation guidelines, developed with the European Society of Cardiology (ESC). EACTS acted following allegations raised in a BBC Newsnight programme about the validity of the conclusions of the EXCEL trial, which were used to inform the recommendations for the treatment of patients with left main coronary artery disease and stable angina. The EXCEL trial investigators have strongly refuted the claims made by Newsnight.
In a separate development, the American Association for Thoracic Surgery (AATS) has called for all of the EXCEL data to “be made publicly available for analysis and interpretation, as a way to resolve the current controversy around the EXCEL trial, in order to provide patients with the best possible counsel and informed consent”.
EACTS’ article, entitled Changing evidence, changing practice, gives an account of its council meeting on 7 December 2019, at which it was unanimously decided to withdraw support from the current recommendations on treatment of left main disease “based on a range of scientific, statistical and professional issues that had been raised”. In addition, the council agreed to notify members and to invite the ESC “immediately to participate in a new joint taskforce to review the LMCAD recommendations in the guidelines”.
Nick Freemantle (Institute of Clinical Trials and Methodology, University College London, London, UK) was asked by the BBC to examine its findings on EXCEL, and EACTS says that Freemantle shared his analysis of the current evidence and the new findings with the EACTS Council. The article outlines that the Council considered Freemantle’s “comprehensive statistical analysis”, as well as several matters of “scientific and professional propriety, including those raised by the BBC, which questioned the robustness of both the content and the guideline process”.
EACTS says that “new emerging evidence” provides “multiple reasons for adapting to these different circumstances”, and reviewing the left main coronary artery disease recommendations. Among these, it says, is data presented by the BBC but not published of the three-year findings from EXCEL using the standard definition of a myocardial infarction (UDMI), which EACTS states “has reversed the perceived advantage/non-inferiority of PCI [percutaneous coronary intervention] compared with CABG [coronary artery bypass graft]”. Additionally, it says, five-year data from EXCEL have now demonstrated a significant survival advantage for CABG over PCI for patients with left main coronary artery disease.
Changing evidence, changing practice also details a range of issues raised by the Newsnight programme. These include that the trial authors have not published the trial outcome data using the universal definition of myocardial infarction (UDMI), hitherto unpublished secondary outcome data using the UDMI that suggested a 35% increased risk of death in the PCI group, emerging mortality data that have not been shared with the EXCEL data safety monitoring board (DSMB), and alleged conflicts of interest.
As a result, says EACTS, it has taken action “to restore confidence in the guidelines”, and has asked the ESC to work with it to develop updated recommendations “as a matter of urgency”.
The statement on transparency of clinical research data issued by the AATS was also a response to the allegations in Newsnight about the conclusions of the EXCEL trial. Signed by AATS president Vaughn A Starnes, and secretary David R Jones, it describes the veracity and transparency of data as fundamental tenets of clinical research trials, and says: “If any member of the treating heart teams, oversight committees, trial investigators, or peer reviewers raise potential serious issues regarding trial data presentation or interpretation, then the best way forward is the public release of all trial data for an independent analysis to confirm that the original trial conclusions are valid. This is particularly true for industry sponsored trials of previously approved devices which are not subject to Government oversight, to reassure the public and physician community that conflicts of interest or unconscious bias has not influenced substantially the design, conduct, reporting, or interpretation of such studies.”
It adds: “The possibility that some patients may have been wrongly advised or treated as a result of current recommendations, which may have been influenced due to incomplete reporting of available data from the EXCEL trial, is a serious matter.”
