The SYNTAXES study is the first study to investigate 10year survival after PCI with drug eluting stents versus CABG in patients with de novo3VD and/or LMCAD. The present analysis is the first study to evaluate the potential relative benefit of PCI versus CABG in terms of all-cause death at 10 years according to prior CEVD in stable patients with complex CAD. The main findings of the present study can be summarized as follows: (1) prior CEVD (14.1%) was common among patients with de novo 3VD and/or LMCAD and they had more comorbidities and more extensive CAD compared with those without CEVD; (2) prior CEVD was associated with a significantly increased risk of all-cause death at 10 years; (3) the relative effects of PCI versus CABG on 10 year all-cause death were similar, irrespective of whether patients had prior CEVD or not.
Patients with CAD often have prior CEVD, which itself is associated with a higher prevalence of CAD [1, 2, 15]. Numerous studies have demonstrated that CAD patients with prior CEVD are more likely to have a diffuse, complex and higher disease burden and multiple comorbidities [3,4,5]. Patients with prior CEVD therefore represent a high risk population and are often excluded from coronary revascularization trials. However, with advances in PCI and CABG techniques, more and more patients with prior CEVD are undergoing revascularization in contemporary practice. In our study, 14.1% of patients who underwent coronary revascularization had a prior history of CEVD, which is comparable to the 12.3% observed in the EXCEL (Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) trial .
Prior CEVD has been shown to be associated with worse clinical outcomes after coronary revascularization [3,4,5, 9, 16]. Indeed, we found that prior CEVD was associated with a significantly increased risk of all-cause death at 10 years in both the PCI and CABG arms. These poorer outcomes may most likely be due to the advanced age and presence of a greater number of comorbidities (peripheral vascular disease, chronic obstructive pulmonary disease, impaired renal function) and cardiac risk factors (diabetes, metabolic syndrome) in the CEVD patient cohort (Table 1), some of which were also found to be independent predictors of 10 year all-cause mortality. These observations were further validated by the fact that history of prior CEVD remained an independent predictor of all-cause death at 10 years and at maximum follow-up (12.6 years)even after multivariate adjustment for important clinical confounders (Online Tables S1 and S2).
The optimal revascularization strategy for complex CAD patients with prior CEVD remains unclear. Stroke is one of the most devastating complications after coronary revascularization, leading to a higher risk of mortality and permanent disability . Most previous studies demonstrated that CABG carried a higher rate of stroke, especially in the periprocedural period [6,7,8, 18]. Hence, in clinical practice, patients with prior CEVD are often referred for PCI instead of CABG. However, recent studies have shown that CABG only increased the risk of perioperative stroke, while the rate of long-term stroke was comparable between PCI and CABG [7, 18,19,20,21]. Moreover, as aforementioned, patients with prior CEVD, who have complex and diffuse CAD and multiple comorbidities, and who undergo PCI may experience increased rates of recurrent cerebrovascular events, myocardial infarction, and death9, [16, 22]. It is important to balance the risk of stroke, which represents the major adverse event of CABG, against the risk of other adverse events such as repeat revascularization, myocardial infarction and death, when determining the optimal revascularization modality between CABG and PCI in patients with prior CEVD [23, 24]. Hence, whether high-risk patients with prior CEVD would benefit from PCI rather than CABG is debatable, and there are only limited data supporting this. In addition, intense pre-operative evaluation of patient risk factors, careful assessment of supra-aortic vessels and ascending aorta for atherosclerotic disease, use of off-pump “no-touch aorta” surgery, monitoring of cerebral oximetry for early detection and treatment of cerebral hypoxia, and prevention and treatment of post-operative atrial fibrillation may reduce the risk of perioperative stroke in CABG-treated patients [25, 26].
Recently, Jamie et al. investigated whether high-risk patients with LMCAD and prior CEVD preferentially benefit from revascularization by PCI compared with CABG in the EXCEL trial. They demonstrated that patients with LMCAD and prior CEVD, when compared with those without CEVD, had higher rates of stroke and reduced event-free survival after revascularization, irrespective of the mode of the revascularization. Overall, patients with prior CEVD had higher rates of stroke at 30 days (2.2 vs. 0.8%; p = 0.05) and 3 years (6.4 vs. 2.2%; p = 0.0003) and higher 3 year rates of the primary endpoint of all-cause death, stroke, or myocardial infarction (25.0 vs. 13.6%; p < 0.0001) . Notably, no data pertaining to the impact of previous CEVD on very long-term (up to 10 years) mortality after revascularization in patients with 3VD and/or LMCAD are available. Not surprisingly, in our present analyses, we demonstrated that prior CEVD was associated with a significantly increased risk of all-cause death at 10 years, with no significant interaction between prior CEVD and revascularization strategy for the relative risk of all-cause death at 10 years. These findings do not support the strategy that patients with prior CEVD should be preferentially referred for PCI rather than CABG. Instead, the heart team  should assess the risk/benefit ratio of CABG versus PCI, by considering the periprocedural surgical risk, anatomical complexity, possibility for complete revascularization, potential procedural complications, benefits of each treatment strategy that emerge over time (beyond the periprocedural period), and patient preferences when selecting the optimal revascularization strategy for 3VD and/or LMCVD patients with prior CEVD.