Abstract

AIMS: An algorithmic strategy for anatomical vs. functional testing in suspected coronary artery disease (CAD) (Anatomical vs. Stress teSting decIsion Support Tool; ASSIST) is associated with better outcomes than random selection. However, in the real world, this decision is rarely random. We explored the agreement between a provider-driven vs. simulated algorithmic approach to cardiac testing and its association with outcomes across multinational cohorts. METHODS AND RESULTS: In two cohorts of functional vs. anatomical testing in a US hospital health system [Yale; 2013-2023; <i>n</i> = 130 196 (97.0%) vs. <i>n</i> = 4020 (3.0%), respectively], and the UK Biobank [<i>n</i> = 3320 (85.1%) vs. <i>n</i> = 581 (14.9%), respectively], we examined outcomes stratified by agreement between the real-world and ASSIST-recommended strategies. Younger age, female sex, Black race, and diabetes history were independently associated with lower odds of ASSIST-aligned testing. Over a median of 4.9 (interquartile range [IQR]: 2.4-7.1) and 5.4 (IQR: 2.6-8.8) years, referral to the ASSIST-recommended strategy was associated with a lower risk of acute myocardial infarction or death (hazard ratio_adjusted: 0.81, 95% confidence interval [CI] 0.77-0.85, <i>P</i> &lt; 0.001 and 0.74 [95% CI 0.60-0.90], <i>P</i> = 0.003, respectively), an effect that remained significant across years, test types, and risk profiles. In <i>post hoc</i> analyses of anatomical-first testing in the Prospective Multicentre Imaging Study for Evaluation of Chest Pain (PROMISE) trial, alignment with ASSIST was independently associated with a 17% and 30% higher risk of detecting CAD in any vessel or the left main artery/proximal left anterior descending coronary artery, respectively. CONCLUSION: In cohorts where historical practices largely favour functional testing, alignment with an algorithmic approach to cardiac testing defined by ASSIST was associated with a lower risk of adverse outcomes. This highlights the potential utility of a data-driven approach in the diagnostic management of CAD.