RESUMO
BACKGROUND: Randomised controlled trials are considered the gold standard for testing the efficacy of novel therapeutic interventions, and typically report the average treatment effect as a summary result. As the result of treatment can vary between patients, basing treatment decisions for individual patients on the overall average treatment effect could be suboptimal. We aimed to develop an individualised decision making tool to select an optimal revascularisation strategy in patients with complex coronary artery disease. METHODS: The SYNTAX Extended Survival (SYNTAXES) study is an investigator-driven extension follow-up of a multicentre, randomised controlled trial done in 85 hospitals across 18 North American and European countries between March, 2005, and April, 2007. Patients with de-novo three-vessel and left main coronary artery disease were randomly assigned (1:1) to either the percutaneous coronary intervention (PCI) group or coronary artery bypass grafting (CABG) group. The SYNTAXES study ascertained 10-year all-cause deaths. We used Cox regression to develop a clinical prognostic index for predicting death over a 10-year period, which was combined, in a second stage, with assigned treatment (PCI or CABG) and two prespecified effect-modifiers, which were selected on the basis of previous evidence: disease type (three-vessel disease or left main coronary artery disease) and anatomical SYNTAX score. We used similar techniques to develop a model to predict the 5-year risk of major adverse cardiovascular events (defined as a composite of all-cause death, non-fatal stroke, or non-fatal myocardial infarction) in patients receiving PCI or CABG. We then assessed the ability of these models to predict the risk of death or a major adverse cardiovascular event, and their differences (ie, the estimated benefit of CABG versus PCI by calculating the absolute risk difference between the two strategies) by cross-validation with the SYNTAX trial (n=1800 participants) and external validation in the pooled population (n=3380 participants) of the FREEDOM, BEST, and PRECOMBAT trials. The concordance (C)-index was used to measure discriminative ability, and calibration plots were used to assess the degree of agreement between predictions and observations. FINDINGS: At cross-validation, the newly developed SYNTAX score II, termed SYNTAX score II 2020, showed a helpful discriminative ability in both treatment groups for predicting 10-year all-cause deaths (C-index=0·73 [95% CI 0·69-0·76] for PCI and 0·73 [0·69-0·76] for CABG) and 5-year major adverse cardiovascular events (C-index=0·65 [0·61-0·69] for PCI and C-index=0·71 [0·67-0·75] for CABG). At external validation, the SYNTAX score II 2020 showed helpful discrimination (C-index=0·67 [0·63-0·70] for PCI and C-index=0·62 [0·58-0·66] for CABG) and good calibration for predicting 5-year major adverse cardiovascular events. The estimated treatment benefit of CABG over PCI varied substantially among patients in the trial population, and the benefit predictions were well calibrated. INTERPRETATION: The SYNTAX score II 2020 for predicting 10-year deaths and 5-year major adverse cardiovascular events can help to identify individuals who will benefit from either CABG or PCI, thereby supporting heart teams, patients, and their families to select optimal revascularisation strategies. FUNDING: The German Heart Research Foundation and the Patient-Centered Outcomes Research Institute.