For more than 20 years, it has been known that untreated significant left main coronary artery (LMCA) disease carries a high mortality rate (50% at 5 years), and that coronary artery bypass grafting (CABG) improves survival compared to medical treatment. However, in this context, no randomized clinical trials (RCTs) have compared percutaneous coronary intervention (PCI) with medical treatment, nor are there recent RCTs comparing CABG with medical treatment. Nevertheless, we currently have five high-quality RCTs comparing PCI (mostly using drug-eluting stents) with CABG to clarify which type of revascularization is most appropriate.

The 2018 ESC/EACTS guidelines on coronary revascularization were based on the 3-year results from the EXCEL and NOBLE trials, but the more recent 2021 ACC/AHA/SCAI guidelines considered the 5-year results of EXCEL and updates from two other RCTs with 10-year follow-up, the SYNTAXES and PRECOMBAT studies. The European guidelines granted a class I PCI recommendation for LMCA disease in cases of low-complexity coronary anatomy and a class IIa recommendation if the complexity was intermediate. However, the American guidelines found it reasonable to recommend PCI (class IIa) when it could provide revascularization comparable to CABG. Unlike RCTs, there are no contemporary observational comparative studies of CABG vs. PCI in LMCA disease, and the few previous ones had limited sample sizes.

The aim of this study was to compare the long-term outcomes of these two revascularization strategies in a real-world setting. To do so, clinical and administrative databases from Ontario, Canada, were linked to identify records of all patients treated by CABG or PCI for significant LMCA disease (angiographic evidence of stenosis ≥50%) between 2008 and 2020. Patients who presented with cardiogenic shock, were candidates for emergent revascularization, and/or had STEMI were excluded from the study. Baseline characteristics were compared between groups, and propensity score matching was performed in a 1:1 ratio. Long-term mortality and a composite of major adverse cardiac and cerebrovascular events (MACCE) were compared between the matched groups using a Cox proportional hazards model. After exclusions, 1299 and 21,287 patients underwent PCI and CABG, respectively. Before matching, PCI patients were older (75.2 vs. 68 years) and a higher percentage were female (34.6% vs. 20.1%), though they had a lower burden of atherosclerosis. Propensity score matching of 25 covariates yielded 1128 well-matched pairs. There were no differences in early mortality between PCI and CABG (5.5% vs. 3.9%). During 7-year follow-up, all-cause mortality (53.6% vs. 35.2%; HR = 1.63; p < 0.001) and MACCE (66.8% vs. 48.6%; HR = 1.77) were significantly higher with PCI compared to CABG.

The authors concluded that CABG was the most common revascularization strategy in this real-world registry. Before propensity score matching, PCI patients were older and at higher risk. After matching, there was no difference in early mortality, but in the long term, CABG provided better survival and greater freedom from MACCE.

COMMENTARY:

This is undoubtedly a particularly relevant study because, for the first time, we have information on clinical outcomes beyond 5 years (7 years) from real-world data of a contemporary cohort of patients with LMCA disease who underwent CABG and PCI. The study’s most notable finding, following propensity score analysis, is that CABG provides significantly better long-term survival and freedom from MACCE compared to PCI, including myocardial infarction and repeat revascularization; only the stroke rate was lower with PCI. Secondary conclusions, but highly descriptive of hospital practice, indicate that CABG remains the preferred revascularization technique for LMCA disease at a ratio of 8:1, and PCI is used in older and more comorbid patients.

Despite the existence of six excellent RCTs comparing CABG with PCI in LMCA disease, the management of this pathology remains controversial. One of the most debated aspects when analyzing these RCTs is the definition of periprocedural myocardial infarction (MI). In the EXCEL study, an MI definition based solely on biochemical markers was used instead of the third universal definition of MI; moreover, the decision was made not to include repeat revascularization as part of the MACCE to be analyzed. Conversely, in Tam et al.’s study, a clinical definition of MI was used, and unlike the EXCEL study results, the incidence of periprocedural MI was higher with PCI (2.8%) than with CABG (1.6%). Interestingly, in studies that reanalyzed the EXCEL study—this time using the third universal definition of MI—it was also observed that the MI incidence was higher in the PCI group (3.3%) than in the CABG group.

In the most recent meta-analysis published in Lancet in 2021 on LMCA revascularization, four of these RCTs with at least 5 years of follow-up were included. The patients analyzed, in comparison with Tam et al.’s study, were at lower risk, younger, and had a lower incidence of diabetes and ventricular dysfunction. All-cause mortality was similar with CABG and PCI; however, if a Bayesian estimation method was applied, increased mortality with PCI was detected. Additionally, the incidence of MI (using the universal definition), repeat revascularization, and composite events were also significantly higher with PCI. Therefore, while not conclusive, the RCT results suggest that CABG in LMCA disease shows a trend towards greater survival (already detectable even at 5 years) and a lower proportion of MACCE (if the universal MI definition is used and repeat revascularization is included).

In contrast to previous observational studies, the majority were not contemporary, had smaller patient populations, and fewer years of follow-up. Nevertheless, the MAIN-COMPARE registry already demonstrated a higher risk of mortality with PCI (despite patients being younger than those in the current study) and a higher incidence of MACCE at 5 years, as well as repeat revascularization at 10 years. Consequently, once again, observational studies on coronary revascularization—closer to “real-world” scenarios—differ significantly from RCTs in terms of long-term outcomes, clearly favoring CABG as the most appropriate therapeutic strategy in most circumstances.

One of the major limitations of this study is the use of data gathered from clinical report summaries to catalog clinical events such as MI or stroke, which is logically less reliable than definitions used in RCTs. The same is true for the incomplete information available on the coronary anatomical complexity of patients (SYNTAX score) and/or the degree of completeness of coronary revascularization. Lastly, in recent years, there have been significant advancements in PCI, which, when applied currently and in the future, will likely continue to improve outcomes for patients with LMCA disease, which may not yet be fully reflected in the results of this study.

Adding the findings of this study to the existing evidence, it should now be clear that in patients with non-high surgical risk and adequate distal vessels from a surgical technical standpoint, CABG remains the revascularization technique of choice for LMCA disease in stable angina and stabilized acute coronary syndrome. The role of PCI is essential for numerous situations involving LMCA disease encountered in daily practice (proximal LMCA disease in patients with severe comorbidities, LMCA disease in frail patients or those with high surgical risk, primary angioplasty, etc.). This study should be taken into consideration in the development of future revascularization guidelines to position CABG favorably over PCI for LMCA disease in the scenarios mentioned above. Of course, this does not preclude the need for longer-term RCTs to confirm the findings of this study.

REFERENCE:

Tam DY, Fang J, Rocha RV, Rao SV, Dzavik V, Lawton J, et al. Real-World Examination of Revascularization Strategies for Left Main Coronary Disease in Ontario, Canada. JACC Cardiovasc Interv. 2022 Dec 28(22)01971-9. doi: 10.1016/j.jcin.2022.10.016.