Anatomical and clinical characteristics to guide decision making between coronary artery bypass surgery and percutaneous coronary intervention for individual patients: development and validation of SYNTAX score II

Summary

Background

The anatomical SYNTAX score is advocated in European and US guidelines as an instrument to help clinicians decide the optimum revascularisation method in patients with complex coronary artery disease. The absence of an individualised approach and of clinical variables to guide decision making between coronary artery bypass graft surgery (CABG) and percutaneous coronary intervention (PCI) are limitations of the SYNTAX score. SYNTAX score II aimed to overcome these limitations.

Methods

SYNTAX score II was developed by applying a Cox proportional hazards model to results of the randomised all comers SYNTAX trial (n=1800). Baseline features with strong associations to 4-year mortality in either the CABG or the PCI settings (interactions), or in both (predictive accuracy), were added to the anatomical SYNTAX score. Comparisons of 4-year mortality predictions between CABG and PCI were made for each patient. Discriminatory performance was quantified by concordance statistics and internally validated with bootstrap resampling. External validation was done in the multinational all comers DELTA registry (n=2891), a heterogeneous population that included patients with three-vessel disease (26%) or complex coronary artery disease (anatomical SYNTAX score ≥33, 30%) who underwent CABG or PCI. The SYNTAX trial is registered with ClinicalTrials.gov, number NCT00114972.

Findings

SYNTAX score II contained eight predictors: anatomical SYNTAX score, age, creatinine clearance, left ventricular ejection fraction (LVEF), presence of unprotected left main coronary artery (ULMCA) disease, peripheral vascular disease, female sex, and chronic obstructive pulmonary disease (COPD). SYNTAX score II significantly predicted a difference in 4-year mortality between patients undergoing CABG and those undergoing PCI (p_interaction 0·0037). To achieve similar 4-year mortality after CABG or PCI, younger patients, women, and patients with reduced LVEF required lower anatomical SYNTAX scores, whereas older patients, patients with ULMCA disease, and those with COPD, required higher anatomical SYNTAX scores. Presence of diabetes was not important for decision making between CABG and PCI (p_interaction 0·67). SYNTAX score II discriminated well in all patients who underwent CABG or PCI, with concordance indices for internal (SYNTAX trial) validation of 0·725 and for external (DELTA registry) validation of 0·716, which were substantially higher than for the anatomical SYNTAX score alone (concordance indices of 0·567 and 0·612, respectively). A nomogram was constructed that allowed for an accurate individualised prediction of 4-year mortality in patients proposing to undergo CABG or PCI.

Interpretation

Long-term (4-year) mortality in patients with complex coronary artery disease can be well predicted by a combination of anatomical and clinical factors in SYNTAX score II. SYNTAX score II can better guide decision making between CABG and PCI than the original anatomical SYNTAX score.

Funding

Boston Scientific Corporation.

Introduction

The anatomical SYNTAX score is an important instrument that can help clinicians to establish the optimum revascularisation approach in patients with complex coronary artery disease (with or without unprotected left main coronary artery [ULMCA] involvement).1, 2, 3, 4, 5 It is advocated in both European and US revascularisation guidelines.6, 7 These guidelines also state that clinical variables should be taken into account during discussion between multidisciplinary teams consisting of a clinical cardiologist, cardiac surgeon, and interventional cardiologist (the so-called heart team approach) when deciding the best treatment method; absence of clinical variables is a limitation of the SYNTAX score.

In patients with ULMCA disease, a low-intermediate SYNTAX score (<33) was shown to have much the same long-term clinical outcomes—including all-cause mortality and major cardiovascular and cerebrovascular events—with coronary artery bypass graft surgery (CABG) and percutaneous coronary intervention (PCI) in the SYNTAX trial.1, 4, 8 This finding formed the basis for the US Food and Drug Administration's decision to accept a SYNTAX score of less than 33 as an entry criterion to the ongoing international multicentre EXCEL (Evaluation of XIENCE prime versus Coronary artery bypass surgery for Effectiveness of Left main revascularisation) trial, aiming to recruit 2600 patients with ULMCA disease (NCT01205776).⁹

In patients with three-vessel disease, a low SYNTAX score (<23) was shown to have much the same long-term clinical outcomes between CABG and PCI in the SYNTAX trial.1, 8 A substudy of the SYNTAX trial¹⁰ has, however, suggested that patients with high clinical comorbidity (ie, additive EuroSCORE¹¹ ≥6) with three-vessel disease, irrespective of the anatomical complexity (SYNTAX score), might potentially derive a prognostic benefit from undergoing CABG compared with PCI, provided an acceptable threshold of operative risk is not exceeded. Some researchers have therefore suggested that the SYNTAX score, and other category-based scores10, 12, 13, 14, 15 that labelled patients as low risk, intermediate risk, or high risk might be concealing higher risk patients in lower risk groups, or vice versa.

The purpose of our study was to augment the SYNTAX score with prognostically important clinical variables to form SYNTAX score II, to better guide decision making between CABG and PCI. Additionally, SYNTAX score II should provide the basis for individualised decision making between CABG and PCI, by contrast with the present strategy of grouping (low, intermediate, or high) risk to patients.