On December 9th, BBC Newsnight came out with an investigation questioning the validity of the 2016 EXCEL clinical trial, led by Dr Gregg Stone, published in the New England Journal of Medicine. Last month, the EXCEL researchers have published an 11-page rebuttal to the BBC report.
The EXCEL clinical trial was a randomized study in 1905 participants that compared the safety and effectiveness of drug-eluding stents to conventional coronary artery bypass surgery for the treatment of left main coronary artery disease, a serious type of heart disease. The study examined the rates of heart attack, stroke, and mortality. The EXCEL study concluded that stents were just as safe and effective as the traditionally used bypass surgery in treating left main coronary artery disease. The trial was sponsored by Abbott, a stent producer, and has received publicity and influenced clinical guidelines.
According to the Newsnight investigation, some key data from the EXCEL trial was withheld. The EXCEL researchers used two different definitions for heart attack, a universal definition and a non-universal definition, to check whether a patient was having a heart attack. The question of which definition of heart attack is the best to use in each situation is debatable. Currently, the EXCEL investigators stand by their decision. However, while the data using the non-universal definition of heart attack was published, the data for the universal definition of heart attack was not. The unpublished data using the universal definition was recently leaked to Newsnight. The unpublished data shows that the group that received a stent had 80% more heart attacks compared to the group that underwent conventional bypass surgery. The lead researchers of the EXCEL trial have disputed the BBC’s findings. In addition to the unpublished heart attack data, the higher mortality rate in the stent group was reportedly downplayed by the trial lead investigators. Follow-up results from the EXCEL trial published last year showed that after five years, patients who were treated with a stent were 35% more likely to have died compared to patients who had undergone heart surgery.
In light of the Newsnight investigation, the European Association of Cardio-Thoracic Surgery (EACTS) has expressed serious concerns regarding the concealed data and is withdrawing its support for the current guidelines for the treatment of left main coronary artery disease. EACTS stated that if the Newsnight investigation is correct, the previous recommendations were unsafe. The other organization involved in the 2018 joint guidelines, the European Society of Cardiology (ESC), has stated that it currently stands by its previous recommendations. The 2018 EACTS-ESC guidelines recommend both stents and bypass surgery for low-risk patients.
According to GlobalData, the global coronary stent market is currently worth over $5 billion and is growing at a Compound Annual Growth Rate of 5%. Drug-eluding stents account for approximately 95% of this market. It is currently unclear how much this controversy will affect the coronary stent market and its growth, if at all. Changes to the EACTS-ESC guidelines are likely to influence surgeons’ choice to use stents for low-risk patients with left main coronary artery disease. Additionally, the fact that this case has been publicised by BBC and hotly debated on social media may alarm the public about coronary stents in general, and thus influence the decisions patients make about their own treatment plans. These factors will affect both Abbott and competitor stent makers.
Finally, this controversy has highlighted possible issues surrounding industry-funded clinical trials and what data, if any, can be omitted from publication, especially when it comes to life-saving procedures. It remains to be seen if it will affect how future clinical trials are conducted and reported.