In this retrospective study, CABG was shown to be superior to PCI with 2nd-generation DESs in young patients with LM and/or three-vessel disease in terms of the incidence of MACCE, which was driven mainly by repeat revascularization. There were no significant differences the hard endpoints death, MI and stoke in line with the outcomes of the recent EXCLE trial (8). After adjustment by propensity-score matching to minimize selection bias, the conclusion was the same as in the overall population. Although this study was limited by its observational design, this is the first report specifically addressing the issue of LM and three-vessel disease in young patients, and it evaluated the potential noninferiority of PCI over CABG. Therefore, our results would be helpful when making a clinical decision in real-world practice, especially for young CAD patients.
It is a good thing that young patients have better baseline characteristics along with fewer and milder complications, so it is essential to consider the broad indications and long-term prognosis. In our study, there were no obvious differences between the two groups in baseline characteristics, except the CABG group had more complex coronary anatomy and lower usage of dual antiplatelets. However, the PCI group showed a higher incidence of MACCE and repeat revascularization.
As in some previous studies, we found that CABG was better than PCI for the composite endpoint of MACCE and repeat revascularization both in LM(6) and three-vessel disease(3, 12, 15). One of the reasons is that after PCI, progressive atherosclerosis can lead to new, severe stenosis and plaque rupture that may cause ischemia and repeat revascularization, and CABG offers better protection by bypassing a large proportion of obstructive lesions or vulnerable plaques, minimizing the impact of progressive disease in the entire upstream proximal vessel (16). Moreover, there was more incomplete revascularization in the PCI group that needed more than one intervention operation, whereas patients achieving complete revascularization showed similar outcomes between PCI and CABG (17). In addition, more routine angiographic follow-up was performed to detect early in-stent restenosis in patients treated with PCI rather than those with CABG. Many patients with PCI receive repeat revascularization that is angiographically rather than clinically driven. Thus, the rate of repeat revascularization might be underestimated for those patients undergoing CABG. We must recognize that with the introduction of high-pressure deployment, use of intravascular ultrasound, and improved stent design, restenosis of drug-eluting stent has diminished over time (10, 18).
Some studies proved that the PCI group had higher rates of MI (19, 20), whereas other studies (21, 22) supported our finding that there were similar rates of MI between the PCI and CABG groups. The main advantage of CABG might be the bypassing of long lesion segments by grafting, which protects, to a great extent, against target lesion MI and proximal de- novo lesion MI (10, 11). The small population and short follow-up time may be two of the reasons that caused the absence of significant differences in MI rates.
While some other studies showed that CABG resulted in significantly higher rates of stoke compared with PCI for LM or multivessel disease (5, 23), we found that the difference in rates was indistinctive. The mechanisms underlying the increased risk of stoke with CABG are likely multifactorial. First, CABG performed on-pump with cannulation and clamping of the aorta increases the rates of stoke, which may be reduced by an off-pump procedure (24). Furthermore, stoke may be less common after PCI due to the routine use of dual antiplatelets after stent implantation. However, in the present study, the CABG group also had higher usage of aspirin and clopidogrel or ticagrelor.
Partly different from Head’s study (25), we and Park et al. shared the same outcome in terms of death to a certain extent (4), i.e., that there was no significant difference in the rate of death between the PCI and CABG groups. The low mortality after treatment in both groups showed that modern revascularization techniques and adjunctive therapy can lead to excellent survival in young patients with LM and three-vessel disease. All these low incidences of MI, stoke and death might relate to the young characteristics of the patients enrolled in our study.
In the subgroup analysis, we found that CABG might lead to higher rates of MACCE in patients who had previously suffered MI, whereas in the opposite patients, PCI caused more MACCE. No relevant studies support this discovery, so it will be important to conduct further studies to see if this finding is generalizable.
In contrast to previous reports involving multivessel or LM disease in part, we found that, along with operation strategy, the predictors of MACCE and repeat revascularization were age, CRP and Gensini score. It is possible that, the inflammation condition and coronary anatomy play an important role in the long-term curative effect, which has been verified by other studies. Kosmoidou et al. (26)found that elevated baseline CRP level was strongly associated with subsequent death, MI and stoke. Misumida et al. (27) detected that SYNTAX score 2 was correlated with mortality. However, some predictors such as diabetes mellitus (28), heart failure (29), chronic renal failure (30) and so on, which proved related to MACCE in other studies, were not included in our finding. From a clinical viewpoint, using these relevant variables that were considered potential predictors of MACCE in young patients with LM and three-vessel disease, represents a first step to implementing further preventive measures and tailored therapies.
Considering the discussion above, patients in the PCI group with a 2nd DES had higher rates of repeat revascularization, which did not translate into a higher incidence of the hard endpoints of MI, stoke and death. A recent meta-analysis and the PRECOMBAT study also supports our results (6, 31). The young age of our patients could explain this result, but it is important to select appropriate operations for long-term survival. The relative benefits of CABG versus PCI with stents in terms of outcomes are highly debated, particularly with each advancement in stent design. Now, the state-of-the art stent is the second-generation DES, which is thinner and is coated with a more biocompatible polymer and new ‘limus’ drugs that allow less inflammation and a lower rate of restenosis compared with first-generation DESs(12, 32, 33). What’s more, with the development of technology, some technique such as IVUS, OCT and kissing balloon may improve prognosis. The kissing balloon can reduce the risk of overall target lesion revascularization while the IVUS and OCT can be used to optimize stenting and guide procedural strategy (34, 35). PCI may also be preferred because of its improved early safety profile.
The internal mammary arteries have been widely used as conduits to the left anterior descending artery due to their long-term patency, and the advantage of CABG may be partially due to the completeness of revascularization (36). Although high long-term patency of the internal mammary artery is expected, some vein graft degeneration can be expected beyond 5 years (10). Multiple arterial grafting is associated with improved survival and a reduced requirement of reintervention compared with grafting of a single internal thoracic artery plus the saphenous vein (37). In the current era, routine use of the right internal mammary artery has not been widely adopted despite its identical histological features to the left internal mammary artery due to technical difficulties and concerns about a potential increase in rates of bleeding and wound complication(20).
Saphenous vein grafts are routinely used in CABG surgery as additional conduits to artery grafts. However, saphenous vein grafts typically present accelerated atherosclerosis resulting in a high rate of stenosis or occlusion of the graft, which contributes to higher morbidity and mortality (38). In the case of graft failure, repeat revascularization after either PCI or CABG is necessary in a certain number of patients, if appropriate. Nevertheless, in addition to an increased operation difficulty, patients undergoing re-CABG have a 2- to 4-fold higher mortality than they do in the first operation, whereas PCI in patients previously treated with CABG is associated with worse acute and long-term outcomes compared with native artery PCI (39, 40).
Our study had some limitations. First, it was a nonrandomized, retrospective study, although we performed propensity-score matching to minimize the potential selection bias and ascertainment bias. Second, the follow-up duration and number of enrolled patients might not be sufficient to evaluate the long-term outcomes of revascularization. Third, this was a single-center study that only included Chinese, and more ethnicities are required in further trials. Fourth, because the treatment choice was left to the physician or patients, selection bias was inevitable. Moreover, some patients who underwent CABG, had the angiography done in outside hospitals rather than our hospital, which affected our evaluation of the lesion. Finally, we used the prevalent SYNTAX score with the Gensini score to estimate the anatomic complexity due to practical considerations.