Scoring systems are designed to assist clinical decision-making. Among them, the SYNTAX score, based on the eponymous clinical trial, quantifies disease severity by assessing the complexity of coronary artery lesions and categorizes cases into three tertiles: low risk (score 0-22), intermediate risk (23-32 points), and high risk (>33 points), being one of the most widely used scores in Cardiology. Its calculation is recommended in the latest European coronary revascularization guidelines of 2018 (Class I, Level of Evidence B) for patients with left main coronary artery disease (LMCA) or multivessel disease.

In clinical practice, the SYNTAX score is commonly applied to choose the revascularization approach (PCI versus CABG) for these patients, with low-risk cases often selected for PCI and high-risk cases for surgical treatment. However, the score was not initially designed for this purpose and has not been prospectively validated.

Gaudino et al. conducted a meta-analysis examining the association between SYNTAX score tertiles and long-term outcomes for major adverse cardiac and cerebrovascular events (MACCE) and all-cause mortality. This analysis included 6 randomized clinical trials evaluating PCI versus CABG in patients with multivessel or LMCA disease, covering a study period from 2004 to 2015 and incorporating data from 8,269 patients (4,134 in the PCI group, 4,135 in the CABG group). Patient samples were consistent across trials and study groups, except for the percentage of diabetic patients, which reached 100% in one study (the FREEDOM trial). The clinical context included patients with stable angina and acute coronary syndrome/unstable angina, with a mean follow-up of 6.2 years. Due to the time frame of these studies, the use of drug-eluting stents and dual antiplatelet therapy (including newer agents such as ticagrelor) was common. In addition, IVUS was utilized in 4 of the trials as a supportive intracoronary diagnostic technique. As for the surgical revascularization techniques, left internal mammary artery grafts were used in 80-90% of cases, with an average of 3 grafts per patient.

For analysis, the incidence rate ratios (IRRs) method was employed as a risk estimator and to generate interaction effects, both in overall estimates and by SYNTAX score subgroups. Various sub-analyses were also conducted for trials involving patients with LMCA and multivessel disease. Overall, PCI was associated with a significant increase in MACCE (IRR 1.39; 95% confidence interval (CI): 1.27-1.51) and a non-significant increase in all-cause mortality (IRR 1.17; CI: 0.98-1.40). In the low-risk SYNTAX score group, these findings were confirmed, with a significant increase in MACCE (IRR 1.25; CI: 1.02-1.54) and a non-significant increase in all-cause mortality (IRR 1.07; CI: 0.76-1.5). In the intermediate-risk group, PCI significantly increased both MACCE (IRR 1.48; CI: 1.30-1.69) and all-cause mortality (IRR 1.38; CI: 1.07-1.77). In the high-risk group, PCI again significantly increased MACCE incidence (IRR 1.39; CI: 1.18-1.63) and non-significantly increased all-cause mortality (IRR 1.03; CI: 0.70-1.52). Tests for treatment effect heterogeneity by SYNTAX score, for both MACCE and mortality, showed no significant results (p-interaction 0.4 and 0.34, respectively). The results were consistent for both LMCA and multivessel disease patients (MACCE: p-interaction 0.85 for LMCA and 0.78 for multivessel; all-cause mortality: p-interaction 0.12 for LMCA and 0.34 for multivessel). Similarly, analysis comparing risk tertiles showed no significant differences.

Given that CABG is associated with better outcomes than PCI for multivessel and LMCA disease regardless of anatomical complexity, the authors conclude that, due to the lack of association between SYNTAX score and clinical outcomes in trials comparing PCI and CABG, the score should be abandoned in favor of multidimensional scores when choosing the revascularization strategy.

COMMENTARY:

This meta-analysis includes 6 significant studies (SYNTAX, EXCEL, NOBLE, BEST, FREEDOM, and PRECOMBAT) assessing PCI versus CABG for LMCA and multivessel disease, with outcomes reported based on pre-treatment SYNTAX scores. Despite possible methodological limitations, this meta-analysis confirms the lack of correlation between SYNTAX score and clinical outcomes, with surgical revascularization proving more favorable across all score levels. Notably, the increased MACCE and mortality rates with PCI, even in lower scores, highlight that PCI is usually chosen for these lower-risk patients as recommended in the latest myocardial revascularization guidelines. It is important to consider that the SYNTAX score is purely angiographic, with considerable interobserver variability. In this type of patient, it seems reasonable to use scores that include clinical parameters when choosing the revascularization strategy, as multiple factors can impact treatment outcomes. Perhaps, in patients not eligible for surgery, the SYNTAX score might help assess PCI viability and technical success. Considering this meta-analysis’ findings, where CABG reduces events and mortality across all score tertiles, it is advisable to discontinue using SYNTAX as the primary tool for revascularization selection, a shift that should be reflected in future clinical guidelines and in our practice.

REFERENCE:

Gaudino M, Hameed I, Di Franco A, Naik A, Demetres M, Biondi-Zoccai G, et al. Comparison of SYNTAX score strata effects of percutaneous and surgical revascularization trials: A meta-analysis. J Thorac Cardiovasc Surg. 2023 Apr;165(4):1405-1413.e13. doi: 10.1016/j.jtcvs.2021.05.036.