ESC and EACTS Announce Review of Left Main Revascularization Guidelines
In light of long-term data from key trials, including EXCEL, European organizations will wade once again into the left main minefield.
(UPDATED) The European Society of Cardiology and European Association for Cardio-Thoracic Surgery (ESC/EACTS) have agreed to review the latest evidence supporting their current revascularization recommendations for patients with left main coronary artery disease.
The decision adds yet another wrinkle to a yearlong and frequently hostile dispute between the surgical and interventional cardiology communities over the EXCEL trial, a study of PCI versus CABG for patients with left main CAD. That trial has come under repeated fire since one of the study’s surgeons broke with the research team following a disagreement over the study findings.
“The European Society of Cardiology and the European Association for Cardio-Thoracic Surgery have agreed to collaborate in reviewing the most up-to-date evidence for the treatment of patients with left main coronary artery stenosis as soon as it is available,” according to a press release announcing the review. “In particular, the organizations wish to review their joint guidelines in the light of emerging, longer-term outcome data from the trials of CABG vs PCI, and an independent patient-level meta-analysis of these trials that is currently under way. The two organizations will establish a robust and transparent process to review this new evidence.”
Colin Baigent, BMBCh (University of Oxford, England), the chair of the ESC committee on practice guidelines, stressed the collaborative working relationship between the two organizations, adding that the soon-to-be assembled review committee will look in detail at all available studies of PCI versus CABG surgery in patients with left main CAD. The individual-patient-data meta-analysis, which is being conducted by an academic medical group outside the auspices of the ESC/EACTS review, includes EXCEL, NOBLE, SYNTAX, and PRECOMBAT. That meta-analysis will also be made available to the task force charged with reviewing the left main chapter of the 2018 ESC myocardial revascularization guidelines.
“That will be able to give us a much clearer insight into the effects of treatment, not just according to the definitions of MI where the main discussion is at the moment but particularly the long-term outcomes,” said Baigent. One of the concerns is that the survival curves crossed over in EXCEL at 5 years such that surgery was favored, he said, and “the only way you’re going to gain any more insight into the balance of benefit for a particular treatment is to carry on following people.”
Under the ESC/EACTS guidelines on myocardial revascularization, which were published in 2018, both PCI and CABG are currently class IA recommendations for patients with left main CAD and a low SYNTAX score (0 to 22). CABG surgery is a class IA recommendation for all patients regardless of anatomical complexity, while PCI is only a class IIa recommendation in left main CAD patients with an intermediate SYNTAX score (23 to 32), meaning it can be considered given that the “weight of evidence/opinion is in favor of usefulness/efficacy.” In patients with highly complex anatomy (SYNTAX score ≥ 33), PCI is not recommended.
A Year On, Still Controversial
The firestorm surrounding EXCEL ignited last year when David Taggart, MD, PhD (University of Oxford, England), the chairman of the EXCEL surgical committee, accused the researchers of downplaying the risk of death with PCI and of concealing data. As a result, EACTS withdrew their support for the guidelines and have long called for an independent statistical review of the data underpinning the 2018 guidelines. Up until now, the ESC had said they stood by the treatment recommendations.
Taggart, who withdrew his name from the New England Journal of Medicine follow-up paper, faulted the EXCEL investigators for failing to publish the UDMI data, which was one of the study’s secondary endpoints. In his opinion, the EXCEL group oversold the merits of PCI based on a composite primary endpoint that included a periprocedural MI definition skewed against surgery. On the heels of his presentation at EACTS, BBC Newsnight followed up with reporting showing that the risk of periprocedural MI was higher with PCI when the Universal Definition was used to ascertain events.
For their part, the EXCEL investigators have long contended they were unable to publish complete UDMI data because cardiac troponin measurements—the preferred biomarker for the Universal Definition—weren’t routinely collected. Just last week, the researchers published a long-anticipated analysis showing that the rates of periprocedural MI after PCI and CABG did indeed vary substantially depending on how infarctions were defined, and as such, so did the primary composite endpoint of death, stroke, and MI.
Overall, the rate of UDMI was significantly higher with PCI than with surgery, although the researchers reported that these events didn’t translate into worse long-term outcomes. On the other hand, their protocol-defined MI endpoint, which combined the Society for Cardiovascular Angiography and Interventions (SCAI) definition for periprocedural MI and the Third Universal Definition for spontaneous MI, was prognostically significant, according to the EXCEL analysis.
To TCTMD, Baigent said that when revelations by the BBC Newsnight program first emerged, it was based largely on rumors and claims that the news organization had access to information that wasn’t in the public realm. At the time, it wasn’t sensible to act without concrete information, he said. “Of course, what’s happened since then is that we’ve had the publication of data from EXCEL that incorporates the Universal Definition of MI and we also have more long-term follow-up data,” Baigent told TCTMD. “I think the long-term follow-up data are really critical for understanding how to advise patients on what treatments are appropriate.”
In addition, the meta-analysis will help inform the review process. “Lots of the discussion has been around EXCEL, but EXCEL is just half the data,” said Baigent. “We mustn’t lose sight of the importance of looking at all the data, to make judgements based on the totality of the evidence, and to make sure all the issues about bias and so forth are considered by the panel. Then we can come up with a fresh, sober revised recommendation. It is entirely for the panel to decide if changes need to be made.”
Baigent said the ESC/EACTS committee reviewing the data will include surgeons, interventionalists, general cardiologists, statisticians, and clinical epidemiologists, among others. The plan is to have a report completed by summer 2021.
Contacted by TCTMD, Taggart said he welcomes the new initiative. “A collaborative review by the ESC/EACTS of the most up-to-date evidence will enhance the robustness of guideline recommendations and restore the confidence of heart teams in making recommendations to individual patients,” he said in an email.
While the ESC/EACTS review is underway, the European organizations recommend treatment decisions for patients with left main CAD “take into account all available published information.” The organizations continue to recommend a discussion with the heart team and patient, as per the current clinical guidelines, for the best individualized treatment option.
Evald Christiansen, MD, PhD (Aarhus University Hospital, Denmark), who led the NOBLE trial, told TCTMD today that he and his colleagues “are most happy to contribute with the NOBLE trial results for the revision of the guidelines” and that they support the individual patient-level-data meta-analysis put forth by the ESC/EACTS. NOBLE was released at the same time as EXCEL in 2016 but found that CABG was superior to PCI at 5 years for a combined MACCE endpoint that did not include periprocedural MIs. He added that the yearlong EXCEL controversy has not been an issue in his everyday interactions with surgeons. “We now have better and much stronger evidence for tailored decision-making at the heart team conference and to have the informed discussion with the patient,” he said in an email.
In the US guidelines, CABG surgery alone has a class I indication for myocardial revascularization of left main CAD. PCI is considered a “reasonable option” (class IIa) in patients with favorable anatomy, such as a low SYNTAX score and ostial or trunk left main CAD, who are at higher risk of surgery. There is a class IIb recommendation—may be considered—for patients with low-to-intermediate SYNTAX scores and a higher risk of surgical complications.