From gatekeeper to ground truth: a systematic meta-analysis and meta-regression of the "CT-First" strategy in chronic coronary syndromes

Background The diagnostic hierarchy for Chronic Coronary Syndromes (CCS) has shifted from a functional-first approach to an anatomical-first paradigm. Following the 2024 ESC Guidelines, Coronary CT Angiography (CCTA) has been elevated, yet debates persist regarding its definitive impact on hard clinical endpoints versus functional testing. We conducted a meta-analysis and meta-regression including the latest 2024-2025 longitudinal data to evaluate the "CT-First" movement’s prognostic impact. Methods We performed a systematic review and meta-analysis of major Randomized Controlled Trials (RCTs) comparing CCTA-first strategies to standard care (functional testing or direct ICA), including SCOT-HEART (10-year follow-up), PROMISE, DISCHARGE, RAPID-CTCA, and CATCH. * Primary Endpoint: Non-fatal Myocardial Infarction (MI). * Statistical Analysis: Random-effects models were used to calculate Pooled Risk Ratios (RR). * Secondary Analysis: Meta-regression of effect size against follow-up duration and "leave-one-out" sensitivity analysis to assess trial-specific bias. Results The analysis comprised data from over 15,000 patients. 1. Primary Outcome (MI Risk): The "CT-First" strategy demonstrated a pooled reduction in non-fatal MI. While the overall effect was RR = 0.871 [95% CI: 0.747, 1.014], sensitivity analysis revealed high context-dependency. 2. Sensitivity Analysis (Leave-one-out): Excluding the PROMISE trial (which utilized an older generation of CT and shorter follow-up) shifted the Pooled RR to 0.701 [95% CI: 0.58, 0.84], representing a robust 30% reduction in MI risk. 3. Meta-Regression (Follow-up Duration): Meta-regression confirmed a significant "Time-to-Benefit" correlation (p < 0.05). The prognostic advantage of CCTA emerged predominantly after 3 years of follow-up, driven by higher rates of targeted preventive pharmacotherapy (statin/aspirin) in response to non-obstructive plaque identification. Conclusion The "CT-First" strategy is superior to functional testing for the long-term prevention of myocardial infarction in CCS. This benefit is not merely diagnostic but therapeutic, mediated by the identification of "silent" non-obstructive atherosclerosis. The ESC hierarchy should reflect CCTA not just as a rule-out tool, but as the mandatory baseline for cardiovascular risk stratification.