The main findings of this study were that the 10 years clinical outcomes for patients with IL were excellent; specifically, they were better than the outcomes of patients with SL who had stented lesions, especially in terms of RVSC rate (5.2% vs. 13.2%). Further, the number of ILs, IL location (RCA), ejection fraction, and hypertension were significantly associated with the occurrence of MACEs during the 10-year follow-up period in patients with SL.
The treatment decisions for ILs are undertaken based on their functional assessment. (5, 8, 22, 23) However, almost 2/3 of the ILs were FFR-negative (FFR > 0.8), and there are no data on the long-term results of stented IL in FFR-positive patients. (24) We expect that stented ILs will have a similar result to the stented culprit lesions. Furthermore, there are insufficient data on the long-term clinical outcomes of ILs that were not stented in patients with SL, and whether risks related to stent placement, such as periprocedural complications, longer-term bleeding, stent thrombosis, the incidence of restenosis, and the cost related to FFR and stenting, are present even in patients with ILs. (25–27)
To the best of our knowledge, this is the first study to examine the impact of ILs that were treated only with optimal medical treatment on the long-term clinical outcomes in patients with SL. MACE and IL-related RVSC rates in patients with SL were associated with the number of ILs but not with ILs themselves. Two important points regarding these results should be considered. First, a single IL did not affect MACE in patients with SL. This suggests that a single IL can be managed using optimal medical treatment alone. Second, the IL-related RVSC rate was only 5.2%, which was considerably lower than that of stented lesions of SL (13.2%) during the 10-year follow up. This result suggests that the total IL-related RVSC rate was acceptably low, especially compared to the rate in patients with stented lesions due to SL, although multiple ILs were a significant predictor of IL-related RVSC rates in this study.
In our study, the number of ILs was an important long-term predictor of MACE and IL-related RVSC rates in patients with SL. We believe that multiple ILs could indicate a type of multivessel disease that represents a systemic atherosclerotic burden resulting from diffuse and pathologic inflammatory processes or endothelial dysfunction. Thus, it is known to be an important predictor of MACE in patients with CAD, (28, 29) as was also observed in our study.
The Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation trial showed that the addition of PCI to optimal medical therapy did not reduce the cardiovascular event risk in patients with stable CAD. (15) The International Study of Comparative Health Effectiveness with Medical and Invasive Approaches trial also showed that invasive intervention was not better than medical therapy alone in patients with stable CAD. (16) The results of these studies showed that routine additional RVSC with stenting strategy did not lead to better outcomes compared to conservative medical treatment in patients with stable CAD. Our study population was different from the two aforementioned studies; that is, we had an all-comer study population, and most culprit lesions were already treated with stenting. Despite these differences, our results showing that the presence of ILs did not affect MACEs in patients with SL who did not receive invasive treatment are consistent with the findings of the previous studies.
An IL occurring in the RCA was a significant predictor of the total RVSC rate and was related to the IL-related RVSC rate and total MACEs in the study subjects. Patients with IL in the RCA had a higher IL-related RVSC rate, although this was not statistically significant in the multivariate analysis. The possible mechanism was unclear, but this result was consistent with previous observational studies showing that CAD in the RCA progresses more rapidly, so stenosis in the RCA may make the patients more likely to develop MACEs than stenosis in other epicardial coronary arteries. (18, 30, 31)
Our study has some limitations. First, due to the single-center, retrospective nature of the study, selection bias could not be excluded. Second, our study analyzed lesion stenosis severity, not lesion length or irregularity, which are also important geometric parameters that affect coronary hemodynamics and resistance. Most ILs analyzed in our study were short; therefore, the lesion length and irregularities did not significantly differ. Third, given that the study lasted for almost ten years, we could not quantify the effects of medications (and changes in medications throughout the study) on the clinical outcomes. Future, large scale, prospectively designed studies can address these limitations and help confirm our results.