Angiography-derived physiology versus alternative strategies for guiding coronary revascularization: Protocol for a systematic review and meta-analysis

Background Angiography-derived physiological assessment has emerged as a wire-free alternative to invasive pressure-wire-based physiology for guiding coronary revascularization. Several randomized controlled trials have investigated its impact on clinical outcomes, using different comparator strategies, including visual angiography, pressure-wire-(PW)-based physiology, intravascular ultrasound (IVUS) and trial-defined usual care. Given the heterogeneity of comparator strategies and the increasing body of randomized clinical evidence, a comprehensive synthesis is warranted. Accordingly, we sought to systematically investigate the impact of angiography-derived FFR-guided revascularization on clinical outcomes in patients with coronary artery disease (CAD) undergoing invasive coronary angiography, in comparison to visual angiography-guided decision making, pressure-wire-based physiological assessment, IVUS-guided intervention and trial-defined usual care. Methods Randomized controlled trials will be identified through systematic searches of PubMed/MEDLINE, Embase and Cochrane CENTRAL. Two reviewers will independently perform study selection, data extraction and risk-of-bias assessment using Cochrane RoB2 tool. The primary outcome will be a composite of all-cause death, any myocardial infarction, and any coronary revascularization at approximately 12 months. Secondary outcomes will include individual cardiovascular endpoints and trial-defined composite outcomes. Separate pairwise meta-analyses will be performed for each comparator category, without pooling across clinically distinct comparator strategies. The primary analysis will use a Bayesian random-effects model to estimate risk ratios and 95% credible intervals, complemented by frequentist random-effects and binomial-likelihood sensitivity analyses. Discussion This meta-analysis aims to clarify the impact of angiography-derived physiology-guided revascularization on clinical outcomes across different comparator strategies. A major strength is the incorporation of final PIONEER IV data, enabling a more comprehensive assessment of the available evidence. The findings may help clarify the role of angiography-derived physiology in contemporary coronary revascularization, inform clinical decision-making and identify areas where further randomized evidence is warranted.