Table 6.
Unmet Issues on Left Main Revascularization
| Topics | Controversial Points (Why This Issue Is Nonuniform Or Undefined? How Can We Resolve This Issue?) |
|---|---|
| MI definition | Because there is still no uniform definition of MI that does not penalize one of the revascularization approaches, different protocol definitions of MI were used in trials comparing PCI and CABG for LMCA disease. The interstudy heterogeneity for MI definitions can result in wide variability across trials and imprecision in estimating the overall treatment effect. Additional studies and efforts by trialists are warranted to improve standardization of the MI definition for future clinical trials comparing PCI and CABG. |
| Complete (CR) or incomplete revascularization (IR) | Reducing the burden of ischemia would improve clinical outcomes, and current evidence supports complete revascularization. Previous studies investigating the clinical impact of CR and IR have lacked standardized definitions of IR. Also, because of inherent selection bias on the results of previous studies, IR was more frequently associated with sicker patients and more anatomically complex CAD. There is a discrepancy in the long-term clinical outcomes of IR between PCI and CABG. In brief, clinical outcomes following IR seem more favorable after CABG than after PCI. Efforts are needed to standardize the definitions of CR and IR in future studies. Further study is required to validate the optimal degree of revascularization and a reasonable level of IR for acceptable long-term outcomes according to the revascularization strategy. Also, it is needed to identify some subsets of patients with LMCA disease who would benefit more from CR. |
| Role of IVUS or FFR | With regard to the clinical impact of IVUS guidance for left main PCI, there has been no large, multicenter, randomized clinical trial. Based on previous observation, IVUS was more frequently used in a substantially younger and less comorbid population, which might have influenced clinical outcomes. These studies rarely included a prespecified protocol for IVUS guidance and stent optimization. Although the potential role of IVUS in reducing LMCA restenosis and stent thrombosis–related complications may be clinically meaningful, a true clinical effect of IVUS guidance for LMCA PCI can be confirmed only through RCTs. Because it is highly unlikely that the efficacy of IVUS guidance in LMCA PCI is tested in RCTs, trials comparing IVUS-guided LMCA PCI with a prespecified optimization protocol vs CABG might provide further insight. CR based on the functional definition is the preferred strategy for PCI. However, the role of functional guidance for CABG is less clear. The clinical use of resting distal coronary pressure-to-aortic pressure ratio and iFR in guiding revascularization of LMCA disease is yet to be fully validated in RCTs. Further RCTs are needed to conclude these issues. |
| All-cause mortality or cardiac mortality | Controversy exists regarding whether all-cause mortality or cardiac mortality is preferred as a study endpoint in RCTs comparing PCI to CABG. There has been a debate over conflicting all-cause and cardiac mortality findings shown in the 5-y results of the EXCEL trial. The use of cardiac-specific mortality may exclude deaths related to the procedure, either through noncardiac mechanisms or because of misclassification. On the other hand, all-cause mortality is the most unbiased endpoint; however, it may lead to oversimplification by including death that is less attributable to the procedure. Efforts should also be made to find a better consensus and definition of cardiac mortality while discussing which mortality endpoint should be preferred. |
| Long-term follow-up data beyond 5 or 10 y | Until recently, long-term follow-up studies comparing contemporary PCI and CABG beyond 5 y were still limited. Limited follow-up could have penalized the CABG group because the long-term benefits of CABG over PCI have not typically been fully evident until 5 to 10 y after the procedure. Also, a substantial interaction between treatment effect and time for the risk of major adverse events was noted in EXCEL and NOBLE. Study participants in EXCEL and NOBLE will be followed up beyond 5 y, which will provide additional valuable information. |
| Optimal antithrombotic strategy and DAPT duration | The optimal strategy for DAPT following complex PCI, such as LMCA bifurcation PCI using the 2-stent technique, still remains unclear. Furthermore, it was suggested that the East Asian population tends to have a higher risk of bleeding events but a relatively lower risk of thrombotic events, namely, the East Asian paradox. A guideline and unique regimen specifically for Asian patients or the unique ischemic/bleeding risk score of Asian patients might be useful in tailoring DAPT for this population. |
| Role of SYNTAX score | The current guideline recommendation for LMCA revascularization is mainly based on the anatomic SYNTAX score. The SYNTAX score failed to clearly differentiate the comparative outcomes between CABG and PCI in EXCEL and NOBLE. The current role of the SYNTAX score as the key factor in decision making for optimal LMCA revascularization needs to be further debated in contemporary clinical practice settings. Also, the SYNTAX score should be interpreted with caution in the context of heart team discussion. |