Development and validation of a tool to stratify the treatment effect of low-dose aspirin in patients with cardiovascular disease: VISTA (Vascular Intervention Stratification Tool for Aspirin)

BackgroundAspirin resistance, as determined by measuring platelet aggregation function, has been investigated as a proxy outcome for clinical treatment failure with low-dose aspirin (occurrence of cardiovascular events despite regular aspirin intake). However, among adults with cardiovascular disease (CVD), there is no method to predict aspirin treatment failure using routinely available clinical data. We aimed to develop and internally validate the Vascular Intervention Stratification Tool for Aspirin (VISTA), a model that predicts inter-individual variability in clinical response to low-dose aspirin. MethodsWe used electronic health records of the Hong Kong Hospital Authority to identify derivation (n=48,743) and validation (n=322,731) cohorts consisting of individuals diagnosed with CVD between January 1, 2015 to December 31, 2018. The composite outcome of recurrent CVD event included the diagnosis of coronary heart disease, ischemic stroke, and peripheral artery disease after low-dose aspirin initiation ([≤] 100 mg). Cox proportional hazards regression with the least absolute shrinkage and selection operator regularization was used to identify the most strongly associated and relevant risk factors for aspirin treatment failure. One-year hazard ratio (HR) was estimated across different risk categories for aspirin treated vs. untreated individuals. ResultsThe derivation cohort included 1,623 individuals who initiated low-dose aspirin after their CVD diagnosis. Among 109 variables available, six were selected as model inputs: atrial fibrillation, dyslipidemia, hyperglycemia, polypharmacy, neutrophilia, and elevated serum creatine kinase. In the model validation cohort, we identified 22,192 individuals who initiated low-dose aspirin and 3,747 individuals without aspirin, other antiplatelets, or anticoagulants. Results of the model validation demonstrated a strong graded association between the number of VISTA risk factors and the one-year risk of CVD. Compared to untreated individuals, low-dose aspirin use with no VISTA risk factors had the lowest HR for CVD (0.68, 95% CI of 0.57 to 0.81). For low-dose aspirin user with 1-2 VISTA risk factors, HRs was 0.87 (0.81 to 0.93). The presence of 3-6 VISTA risk factors was associated with aspirin treatment failure (HR 0.99; 95% CI of 0.88 to 1.12), which occurred in approximately 20% of patients in our validation cohort. ConclusionsVISTA can predict the heterogeneity of low-dose aspirins treatment effect against recurrent CVD. VISTA could be used to stratify patients based on six readily available risk factors and inform patients and clinicians about the potential benefits of aspirin therapy and the potential for alternate antiplatelet treatments. Clinical perspectiveO_ST_ABSWhat is new?C_ST_ABSO_LIWe developed VISTA (Vascular Intervention Stratification Tool for Aspirin), the first tool that enables the stratification of low-dose aspirin treatment effect for the secondary prevention of cardiovascular disease (CVD). By utilizing six easily accessible clinical risk factors (atrial fibrillation, dyslipidemia, hyperglycemia, polypharmacy, neutrophilia, and elevated serum creatine kinase), VISTA allows for the assessment of aspirin suitability before prescription. C_LIO_LIVISTA can differentiate patients who are likely to benefit significantly from aspirin treatment (0 risk factors, hazard ratio [HR] of 0.68) from those who may experience aspirin treatment failure (3-6 risk factors, HR of 0.99). C_LI What are the clinical implications?O_LIEstimated from a high-quality contemporary validation cohort, there are approximately 20% of patients with CVD who may experience aspirin treatment failure. C_LIO_LIBy utilizing VISTA, healthcare providers can personalize aspirin treatment, optimizing its effectiveness and minimizing the potential for treatment failure. This tool empowers clinicians to make more accurate and tailored decisions in prescribing low-dose aspirin for secondary prevention of cardiovascular disease, ultimately leading to improved patient outcomes. C_LI