Refined selection of individuals for preventive cardiovascular disease treatment with a transformer-based risk model.

Background: Although statistical models have been commonly used to identify patients at risk of cardiovascular disease for preventive therapy, these models tend to over-recommend therapy. Moreover, in populations with pre-existing diseases, the current approach is to indiscriminately treat all, as modelling in this context is currently inadequate. This study aimed to develop and validate the Transformer-based Risk assessment survival (TRisk) model, a novel deep learning model, for predicting 10-year risk of cardiovascular disease in both the primary prevention population and individuals with diabetes.

Methods: An open cohort of 3 million adults aged 25-84 years was identified using linked electronic health records from 291 general practices, for model development, and 98 general practices, for validation, across England from 1998 to 2015. Comparison against the QRISK3 score and a deep learning derivation of it was done. Additional analyses compared discriminatory performance in other age groups, by sex, and across categories of socioeconomic status.

Findings: TRisk showed superior discrimination (C index in the primary prevention population 0·910; 95% CI 0·906-0·913). TRisk's performance was found to be less sensitive to population age range than the benchmark models and outperformed other models also in analyses stratified by age, sex, or socioeconomic status. All models were overall well calibrated. In decision curve analyses, TRisk showed a greater net benefit than benchmark models across the range of relevant thresholds. At the widely recommended 10% risk threshold and the higher 15% threshold, TRisk reduced both the total number of patients classified at high risk (by 20·6% and 34·6%, respectively) and the number of false negatives as compared with recommended strategies. TRisk similarly outperformed other models in patients with diabetes. Compared with the widely recommended treat-all policy approach for patients with diabetes, TRisk at a 10% risk threshold would lead to deselection of 24·3% of individuals, with a small fraction of false negatives (0·2% of the cohort).

Interpretation: TRisk enabled a more targeted selection of individuals at risk of cardiovascular disease in both the primary prevention population and cohorts with diabetes, compared with benchmark approaches. Incorporation of TRisk into routine care could potentially reduce the number of treatment-eligible patients by approximately one-third while preventing at least as many events as with currently adopted approaches.

Funding: None.