A meta-analysis comparing percutaneous coronary intervention (PCI) using a drug-eluting stent (DES) to coronary artery bypass graft (CABG) surgery in patients with left main coronary artery disease has concluded there is no statistically significant difference between the two strategies in terms of mortality at five years.
However, the analysis, which was led by the Thrombolysis in Myocardial Infarction (TIMI) Study Group at Brigham & Women’s Hospital in Boston, USA, did find that there were differences between the two strategies in terms of lower rates of spontaneous myocardial infarction (MI) and repeat revascularisation with CABG, as compared with a lower incidence of early stroke with PCI. Differences in the risk of procedural MI depended on the definition used, researchers found.
TIMI Study Group chairman Marc Sabatine (Brigham and Women’s Hospital and Harvard Medicine School, Boston, USA) presented findings of the analysis at the American Heart Association’s Scientific Sessions 2021 (AHA 2021; 13–15 November, virtual), which were simultaneously published in The Lancet.
“Differences in trial composite endpoints and findings have led to persistent uncertainty among clinicians and practice guideline committees regarding the optimal revascularisation strategy,” Sabatine told AHA attendees. In order to address some of this controversy, Sabatine and colleagues from the TIMI Study Group set about analysing data from the four biggest randomised trials to examine revascularisation strategies in patients with left main coronary artery disease to date—SYNTAX, PRECOMBAT, NOBLE and EXCEL—comprising nearly 4,400 patients in total.
Independent investigators, including non-interventional cardiologists, an interventional cardiologist, a cardiac surgeon and a statistician, as well as principal investigators of the four trials, all participated in the analysis. The primary endpoint was all-cause mortality through five years, with secondary endpoints including cardiovascular death, spontaneous MI, procedural MI, stroke and repeat coronary revascularisation. Investigators also performed landmark, supplemental analyses using 10-year data from the SYNTAX and PRECOMBAT trials, as well as a Bayesian analysis to quantify the probability and magnitude of any difference in mortality.
Sabatine detailed that, overall, there was no statistically significant difference in mortality between the two treatment strategies despite an early diversion of the curves—in favour of PCI—that then crossed. The five-year rates of mortality stood at 11.2% for PCI, compared to 10.2% for CABG, Sabatine reported.
In an attempt to further quantity the potential differences, a Bayesian analysis showed that there was an 86% probability that mortality was greater with PCI versus CABG, but only a 49% probability that the excess was 1% or more over five years, Sabatine detailed. “In other words, the difference was more likely than not less than 0.2% per year,” he told the AHA audience.
Detailing the combined data from the trials to have followed patients out to 10 years, Sabatine noted that the rates of mortality also appeared to be similar, standing at 21.6% in the PCI arm and 22.1% in the CABG arm.
In terms of secondary outcomes, Sabatine explained that patients treated with PCI had more than twice the risk of having a spontaneous MI (6.2% vs 2.6%), with an absolute risk difference over five years of 3.5%. Likewise, he noted that patients treated with PCI had nearly twice the rate of repeat revascularisation (18.3% vs. 10.7%), with an absolute risk difference of 7.6%.
Regarding procedural MI, Sabatine explained that each of the four trials had a prespecified primary definition, which, when using these definitions, showed that there were around one third fewer procedural MIs with PCI. “This was consistently seen in all four trials,” Sabatine commented. Two trials—SYNTAX and EXCEL—were reanalysed using the universal definition of MI (UDMI), which in turn suggested that there was no significant difference between CABG and PCI. “If anything, the pattern was reversed,” Sabatine commented.
With regard to stroke, he noted that there was no statistically significant difference between the two arms through five years (PCI=2.7% vs. CABG=3.1%), but he did note that, as apparent from the shapes of the cumulative incidence curves, the relationship differs early versus late. “In the first year there was a lower rate of stroke with PCI, with almost a two thirds reduction of risk, and an absolute risk difference of 1%. Convincingly, this pattern was seen in all four trials,” Sabatine commented.
“Of course for any given patient our findings need to be put into the context of factors that must be taken into account when deciding on a revascularisation strategy,” Sabatine said, summarising the findings. “The complex nuances of these data emphasise the importance of a heart team approach to assist patients in reaching a treatment decision that is best for them.”
Speaking to Cardiovascular News, Sabatine said that the continuing controversy surrounding left main revascularisation had provided the rationale for the study.
“There has remained intense debate in the field, you need only look at Twitter, to how to approach this,” he said. “So to try to bring clarity to the field there was a call for having an independent group of experienced researchers gather the data and put them all together, and with all the data together hopefully provide a more complete picture that practitioners could use to guide the discussions they have with their patients about which revascularisation approach might be better for that particular patient.”
Sabatine said he hoped that the review of data by the TIMI Study Group would provide some reassuring data for interventional cardiologists, cardiac surgeons and patients alike when considering treatment strategies.
“Guideline committees have been waiting for this analysis so they can come together and make a recommendation,” Sabatine added, referring to the ongoing review by the European Society of Cardiology (ESC) and the European Association for Cardiothoracic Surgery (EACTS) of available evidence for the treatment of patients with left main coronary artery stenosis.
Discussing some of the controversy surrounding the debate around revascularisation strategies in left main coronary artery disease, Sabatine said he hoped that the findings of the analysis would help to “move the conversation forward”.
“Both interventional cardiologists and the cardiac surgeons all have the same goal of doing the right thing for the patient in front of them and are appropriately passionate about the approach that they can offer,” he commented. “I think that the advantage here is that, as the saying goes, people are entitled to their own opinions, but not to their own facts. This should create some common ground. Rather than people just looking at one study or taking issue with a composite endpoint, this allows one to really unpack all of the issues by a neutral third party.
“This was a collaboration between independent investigators and the principal investigators for the trials, and for each trial there were interventionalists and surgeons. For the independent investigators, it is a mix of non-interventional cardiologists, an interventional cardiologist, a cardiac surgeon, [and] a statistician, so that is the right balanced mix. Now everyone has the same set of facts in front of them, and so I think that should help the conversation move forward, because everyone is starting on the same page.”