EACTS Offers to Help to Resolve EXCEL Controversy, as CRF Launches Review
The surgical society said they would be supportive of independent data analyses in order to restore validity to the trial.
The European Association of Cardio-Thoracic Surgery (EACTS) has reached out to the EXCEL principal investigators and offered their assistance to resolve concerns surrounding the controversial clinical trial. The move comes as the Cardiovascular Research Foundation (CRF) announced it has commissioned an independent review and said, in a statement provided to TCTMD, that the organization is available to assist other groups in a review of the EXCEL trial.
Since the publication of the 5-year results during TCT 2019, the trial has been dogged by accusations of suppressed data, specifically MI events adjudicated using the universal definition, and unheeded safety concerns. Sponsored by Abbott Vascular, EXCEL was a head-to-head comparison of CABG surgery versus PCI with the everolimus-eluting metallic stent in patients with unprotected left main coronary artery disease.
In a letter written on behalf of EACTS, emailed to the EXCEL investigators and posted online, secretary-general Domenic Pagano, MD (University Hospitals/Queen Elizabeth Hospital, Birmingham, England), said action is needed to “reestablish the validity” of the study and urged the investigators to make individual patient data available for independent analysis. Specifically, Pagano recommends these data be given to trial scientists from the Institute of Clinical Trials and Methodology at University College London.
“This institution could reanalyze the EXCEL data independently and on your behalf. EACTS would be supportive of such an initiative and provide all necessary support,” writes Pagano in the January 6, 2020, letter to Gregg Stone, MD (Icahn School of Medicine at Mount Sinai, New York, NY), Patrick Serruys, MD (Erasmus Medical Center, Rotterdam, the Netherlands), Joseph Sabik III, MD (University Hospitals Cleveland Medical Center, OH), and A. Pieter Kappetein, MD (formerly Erasmus Medical Center, the Netherlands, and now Medtronic).
If the EXCEL investigators choose another group to reanalyze the data, Pagano recommends that EACTS be “directly involved to provide the independence and the breadth of expertise that this exercise deserves.” He also states that the European Society of Cardiology’s involvement would be “desirable and appropriate.”
In the statement provided to TCTMD announcing CRF’s independent review, the organization specified that they were paid by the study sponsor to organize the clinical endpoint committee and to perform analytical and other related services.
CRF’s statement asserts: “Other than providing these services, CRF had no role in the conduct of the trial. Because of our commitment to excellence, we have commissioned an independent review of the matter. We are also available to assist the relevant societies and medical academies to ensure a comprehensive review of available data from the EXCEL trial. Dr. Gregg Stone (who is not an employee of CRF) continues to be involved with the organization.”
The website for CRF’s Clinical Trial Center lists its EXCEL trial involvement as: principal investigator, data management and analysis, angiographic core lab, and IVUS core lab. Stone is Co-Director of Medical Research and Education at CRF, which is also the publisher of TCTMD.
Controversy Explodes After Investigator Breaks From EXCEL
In December 2019, following a BBC Newsnight report of missing MI data, EACTS withdrew their support for the current treatment recommendations for left main coronary artery disease in the 2018 European myocardial revascularization guidelines.
Controversy surrounding EXCEL first erupted when David Taggart, MD, PhD (University of Oxford, England), the chairman of the surgical committee during the design and recruitment phase of the trial, broke from the principal investigators over the interpretation of the 5-year results. Taggart criticized the group for downplaying the increased risk of mortality with PCI, as well as for not presenting complete MI data as defined by study’s protocol.
Following those accusations, the EXCEL leadership issued an extensive response in December, explaining that cardiac troponin measurements were infrequently collected and this limited their ability to assess MI using the Third Universal Definition. In a response signed by 11 investigators, they said they will soon publish more MI data, including rates and implications of MI according to the study’s protocol definition, the Third Universal Definition using CK-MB data, and other definitions, if possible, such as those from the Society of Cardiovascular Angiography and Interventions and ARC-2.
The response, however, didn’t satisfy Taggart, who fired back at the group insisting that concerns surrounding mortality and MI rates remain. To TCTMD, Taggart has previously stated he supports the EACTS position to have EXCEL reanalyzed by independent clinician scientists and statisticians.
European Association of Cardio-Thoracic Surgery. Letter to the EXCEL primary investigators. Published on: January 6, 2020. Accessed on: January 8, 2020.