[Q's For Author] Lead MAIN-COMPARE Author Hashes Out Study Insights

Professor Yoon Yong-hoon, MAIN-COMPARE lead author, reveals major findings, hashes thoughts on EXCEL and NOBEL, and discusses study limitations and prospects in in-depth interview

The 10-year MAIN-COMPARE study published by Korean researchers in February highlighted the importance of the SYNTAX score in predicting long-term benefits of coronary revascularization with PCI and CABG in patients with left main (LM) coronary artery disease and low-to-intermediate anatomic complexity.1

The research team, led by Professor Yoon Yong-hoon (Chungnam National University Hospital, Daejeon, South Korea) and Professor Park Duk-woo (Asan Medical Center, Seoul, South Korea), found that the 10-year risk for death and other clinical outcomes were similar between PCI and CABG, although PCI proved to be associated with a higher risk for death in patients with a high SYNTAX score.

In light of these findings published in JACC: Cardiovascular Interventions, SUMMIT-MD met with lead study author Yoon to discuss major findings of MAIN-COMPARE, the EXCEL trial findings, and future possible studies.

Q: What are the major findings of the MAIN-COMPARE study?

Answer: We found long term-safety of PCI in LM disease patients with a low-to-intermediate SYNTAX score. However, all clinical outcomes favored CABG over PCI in the high SYNTAX score group. The SYNTAX score also had a prognostic ability only in the PCI arm, but not in the CABG arm.

Q: What other insights does the MAIN-COMPARE study offer?

A: The differential effect of CABG and PCI according to the SYNTAX score grade is caused by the mechanism of revascularization modalities. The CABG is immune to the state of atherosclerotic burden at proximal site to target lesion, because the grafts bypass tortuous angle, diffuse lesions, bifurcation, and calcification. Meanwhile, higher anatomic complexity requires more stents and complex techniques, which leads to a higher chance of restenosis in PCI.

Q: Can you describe the study and how it compares to other trials that looked at PCI vs. CABG in LM coronary artery disease?

A: The recently published long-term data from the SYNTAX trial produced similar results to MAIN-COMPARE. Both studies showed no difference in 10-year mortality in patients with a low-to-intermediate SYNTAX score, but higher mortality in those with a high SYNTAX score. The MAIN-COMPARE and SYNTAX trials both used first-generation drug-eluting stents, which may have contributed to producing similar results. The EXCEL and NOBEL trials, which produced longer-term outcomes using newer generation drug-eluting stents, may provide more information about the safety and efficacy of second-generation drug-eluting stents.

Q: What is the importance of these novel findings and what are the clinical applications?

A: To date, data regarding long-term outcomes of LM revascularization has been lacking. The treatment effect of two modalities differs over time, possibly due to factors such as the late catch-up phenomenon. In this regard, we needed long-term outcomes to guide patients to optimal treatment. The MAIN-COMPARE trial serves as valuable evidence for PCI as a safe and alternative option for LM disease, especially in the low-to-intermediate SYNTAX score population.

Q: How would you interpret the findings from the EXCEL and NOBEL trials? The 5-year trials showed a limited discriminative capacity of the SYNTAX score in predicting differential outcomes after PCI and CABG.

A: If you look at these trials in-depth, these landmark trials only enrolled a ¡°randomizable¡± population that had a low-to-intermediate SYNTAX score on-site. This resulted in a low number of patients with a high SYNTAX score in the core lab, and these patients were then categorized into low-to-intermediate SYNTAX score groups on-site. In these trials, the true population with a large atherosclerotic burden was low, and this may have led to a limited SYNTAX score capability.

Q: What is the clinical application of the SYNTAX and SYNTAX-II score, and which is more important?

A: There are two things to consider here. First is that only the anatomic complexity in coronary revascularization leads to unfavorable outcomes for patients. Second is that we all agree with the importance of age, LV ejection fraction, renal function, and other elements for the SYNTAX II score. In this regard, the SYNTAX II score may serve as better guidance for selecting an optimal revascularization strategy for LM disease.

Q: When making decisions for multi-vessel or left main revascularization, do you routinely use the SYNTAX or SYNTAX II score in daily practice?

A: We don¡¯t calculate SYNTAX score for every patient with LM or multi-vessel disease, but it is carefully considered when coronary lesions are thought to be within the range of an intermediate-to-high SYNTAX score and if the patient is open to two treatment options. This is because we all agree with the fact that the SYNTAX score is a reliable tool for guiding patients with LM or multi-vessel coronary disease.

Q: Do you have any thoughts on the EXCEL trial controversy based on your study?

A: It¡¯s important we interpret the recent EXCEL trial controversy carefully. Investigators observed higher mortality in the PCI group, and this may be because of the increased risk of repeat revascularization. Another aspect worth mentioning is that SYNTAX and MAIN-COMPARE showed no differences in mortality, so we need much longer-term outcomes to confirm the mortality risk.

Q: How might your findings impact practice?

A: In the past five years, we had little knowledge regarding the clinical prognosis of the two treatment options due to data scarcity. We can now perform PCI in patients with LM disease with a low-to-intermediate SYNTAX score with more evidence, having seen the long-term outcomes of similar safety results between PCI and CABG. We can discuss the results of the study with our patients and heart teams, which helps us decide the next course of action for patients to achieve better outcomes.

Q: Are there any study limitations such as factors that would reduce the relevance of these findings for European or American patients?

A: Even though we adjusted baseline clinical profiles of both PCI and CABG groups with inverse-probability-weighting analysis, this is not a randomized controlled trial. And the stents used in the study period (bare-metal stent and first-generation drug-eluting stent) are not used in current practice. So the study limitations would include the selection bias and used stent devices, which are currently not available.

Q: What are your next steps? Will there be a follow-up analysis in the study population?

A: I believe a 10-year follow-up would be enough to assess the long-term benefit of two coronary revascularization modalities. Going forward, we have to think about what further insight we can obtain from this population. Important factors such as age, sex, and LV ejection fraction, among others, can play a role in deciding on LM revascularization. To date, long-term outcomes regarding these factors are nonexistent.

  1. https://interventions.onlinejacc.org/content/13/3/361?_ga=2.3381232.171783738.1592270890-403549449.1592270890

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