Estimation of recurrent atherosclerotic cardiovascular event risk in patients with established cardiovascular disease

Aims The 10-year risk of recurrent atherosclerotic cardiovascular disease (ASCVD) events in patients with established ASCVD can be estimated with the Secondary Manifestations of ARTerial disease (SMART) risk score, and may help refine clinical management. To broaden generalizability across regions, we updated the existing tool (SMART2 risk score) and recalibrated it with regional incidence rates and assessed its performance in external populations. Methods and results Individuals with coronary artery disease, cerebrovascular disease, peripheral artery disease, or abdominal aortic aneurysms were included from the Utrecht Cardiovascular Cohort-SMART cohort [n = 8355; 1706 ASCVD events during a median follow-up of 8.2 years (interquartile range 4.2-12.5)] to derive a 10-year risk prediction model for recurrent ASCVD events (non-fatal myocardial infarction, non-fatal stroke, or cardiovascular mortality) using a Fine and Gray competing risk-adjusted model. The model was recalibrated to four regions across Europe, and to Asia (excluding Japan), Japan, Australia, North America, and Latin America using contemporary cohort data from each target region. External validation used data from seven cohorts [Clinical Practice Research Datalink, SWEDEHEART, the international REduction of Atherothrombosis for Continued Health (REACH) Registry, Estonian Biobank, Spanish Biomarkers in Acute Coronary Syndrome and Biomarkers in Acute Myocardial Infarction (BACS/BAMI), the Norwegian COgnitive Impairment After STroke, and Bialystok PLUS/Polaspire] and included 369 044 individuals with established ASCVD of whom 62 807 experienced an ASCVD event. C-statistics ranged from 0.605 [95% confidence interval (CI) 0.547-0.664] in BACS/BAMI to 0.772 (95% CI 0.659-0.886) in REACH Europe high-risk region. The clinical utility of the model was demonstrated across a range of clinically relevant treatment thresholds for intensified treatment options. Conclusion The SMART2 risk score provides an updated, validated tool for the prediction of recurrent ASCVD events in patients with established ASCVD across European and non-European populations. The use of this tool could allow for a more personalized approach to secondary prevention based upon quantitative rather than qualitative estimates of residual risk. Key objective To improve upon prediction of 10-year residual atherosclerotic cardiovascular disease (ASCVD) event risk in individuals with established ASCVD, by taking into account competing risks and geographical differences in ASCVD incidence. Key findings Derivation in 8355 individuals with established ASCVD from the Utrecht Cardiovascular Cohort-Secondary Manifestations of ARTerial disease (SMART) cohort. C-statistics ranged from 0.605 [95% confidence interval (CI) 0.547-0.664] to 0.772 (95% CI 0.659-0.886). Clinical utility was demonstrated across a range of treatment thresholds relevant to therapy intensification. Take-home messages The SMART2 risk score can be used to estimate 10-year residual risk of fatal and non-fatal ASCVD in individuals with established ASCVD. Adapted to the CVD incidence in several global regions. Facilitates shared decision-making on Step 2 prevention goals as recommended by the 2021 ESC Guidelines on cardiovascular prevention.