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In patients with moderate- and high-risk acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI), the Syntax score predicts 1-year ischemic outcomes including mortality, according to an observational analysis published in the June 14, 2011, issue of the Journal of the American College of Cardiology. The finding suggests that this angiographic assessment of lesion complexity may be a useful tool for risk stratification, the authors say.

To evaluate the prognostic ability of the Syntax score, a team led by Gregg W. Stone, MD, of Columbia University Medical Center (New York, NY), looked at the outcomes of 2,627 non-ST-segment elevation (NSTE) ACS patients from the ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) trial who had quantitative coronary angiography and underwent PCI.

In ACUITY, patients with NSTE ACS were randomized to heparin plus a glycoprotein IIb/IIIa inhibitor (GPI), bivalirudin plus a GPI, or bivalirudin monotherapy with bailout GPI use. After angiography, they were treated with PCI, CABG, or medical therapy, depending on coronary anatomy. The Syntax score previously has been validated as a predictive tool in patients with stable ischemic CAD and multivessel or left main disease in several trials, notably the randomized SYNTAX trial (Serruys PW, et al. N Engl J Med. 2009;360:961-972).

For the ACUITY substudy, scores were calculated using the Syntax algorithm. Patients were then stratified into tertiles based on the results:

• Low score: less than 7 (n = 854)
• Intermediate score: 7 to less than 13 (n = 825)
• High score: 13 or greater (n = 948)

Syntax scores ranged from 0 to 59 with a median of 9. Compared with patients in the lower tertiles, those in the highest tertile were older and more likely to have diabetes, renal dysfunction, baseline troponin elevation, ST-segment deviation, higher TIMI risk score, and lower LVEF. They also were more likely to have longer lesions, bifurcation lesions, thrombus-containing lesions, and heavily calcified lesions.

Highest Tertile Marks Threshold for Worse Outcomes

At 1-year follow-up, all-cause death had occurred in 2.4% of patients in the overall cohort, cardiac death in 1.3%, MI in 9.3%, and TVR in 8.1%. Stratified by Syntax score, these outcomes were significantly more common in the highest tertile than the 2 lower tertiles. There were no differences between the intermediate and low tertiles (table 1).

Table 1. One-Year Clinical Outcomes by Syntax Score Tertile

^a For the high vs. intermediate tertile.

After multivariable adjustment, Syntax score was an independent predictor of all 1-year ischemic endpoints:

• All-cause death (HR 1.04; 95% CI 1.01-1.07; P = 0.005)
• Cardiac death (HR 1.06; 95% CI 1.03-1.09; P = 0.0002)
• MI (HR 1.03; 95% CI 1.02-1.05; P < 0.0001)
• TVR (HR 1.03; 95% CI 1.02-1.05; P < 0.0001)

In receiver operating curve analysis, the optimal Syntax score cutoff value ranged from 10 to 13 depending on the outcome. Landmark analyses showed that rates of all-cause death, cardiac death, and MI were increased among patients with a higher Syntax score at both 30 days and 1 year, whereas the incidence of TVR was elevated in high Syntax score patients mainly within the first 30 days after PCI.

In addition, the predictive value of a high Syntax score was consistent across multiple prespecified subgroups, including the elderly and patients with diabetes, renal dysfunction, positive biomarkers, and a low LVEF.

The authors note that although several studies have identified clinical and laboratory variables that correlate with a poorer prognosis in ACS patients, the role of anatomic and angiographic variables has not been firmly established, although the ability of the Syntax score to predict MACE and mortality recently was validated in the all-comers LEADERS trial (Wykrzykowska JJ, et al. J Am Coll Cardiol. 2010;56:272-277).

Combining Angiographic and Clinical Assessments

Despite the strong showing by the Syntax score, however, the investigators observe that “risk scores incorporating both clinical and angiographic variables may be more accurate than those including either alone.”

In an e-mail communication with TCTMD, Joanna J. Wykrzykowska, MD, of Academic Medical Center (Amsterdam, The Netherlands), concurred, noting that “in complex patients such as ARTS patients (Garg S, et al. Circ Cardiovasc Interv. 2010;3:317-326) the Clinical Syntax Score [including age, LVEF, and creatinine clearance] increased the accuracy and predictive value of the Syntax score.” However, she pointed out, “in patients at lower risk such as in LEADERS (Wykrzykowska JJ, et al. Circ Cardiovasc Interv. 2011;4:47-56), [clinical assessment] did not have much additive value.” On the other hand, that may simply have been due to distortion caused by the complexity of the methodology used, she added.

Whether a hybrid approach is useful for ACS patients deserves further investigation, the current study authors observe. 

Low Cutpoint Broadens Score’s Applicability 

A distinctive feature of the current study is the demonstration that outcomes in ACS patients can be predicted by Syntax score at a very low cutoff value, Dr. Stone noted in an e-mail communication with TCTMD. “This underlines the importance of angiographic variables for risk stratification,” he wrote. “Specifically, while most people consider a high Syntax score a risk factor for restenosis, in ACUITY it even more strongly predicted subsequent mortality and MI than TVR. Moreover, the [low] cutoff for increased risk means that many patients we treat with PCI in ACS can be risk-stratified by the Syntax score.”

He added that “although calculating the Syntax score is perceived by some to be burdensome (and has a distinct learning curve), these data should motivate physicians to learn [to calculate] the score and apply it to most of their patients requiring revascularization.” 

Dr. Wykrzykowska agreed, noting that “using the [Syntax] Web site, it only takes a minute to calculate the score after you’ve looked at the films. And it forces you to look at the films more carefully so that you notice potential difficulties and improve your PCI procedure planning.” 

Dr. Stone concluded, “Future studies will determine whether the Syntax score in patients with ACS should guide revascularization decisions (eg, PCI vs. CABG vs. medical therapy, as it did for left main and 3-vessel disease in the SYNTAX trial) or perhaps dictate a more or less liberal use of staging.” 

Study Details 

The Syntax score of each angiogram was assessed by 3 experienced interventional cardiologists blinded to the treatment assignments and clinical outcomes.

In patients undergoing PCI, the choice of BMS or DES was at the operator’s discretion. There were no significant differences in discharge use of aspirin, clopidogrel, or ticlopidine across the Syntax score tertiles.

Note: Dr. Stone and several coauthors are faculty members of the Cardiovascular Research Foundation, which owns and operates TCTMD.

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