Does geographical variability influence five-year MACCE rates in the multicentre SYNTAX revascularisation trial?

Aims: The use of multiple geographical sites for randomised cardiovascular trials may lead to important heterogeneity in treatment effects. This study aimed to determine whether treatment effects from different geographical recruitment regions impacted significantly on five-year MACCE rates in the SYNTAX trial. Methods and results: Five-year SYNTAX results (n=1,800) were analysed for geographical variability by site and country for the effect of treatment (CABG vs. PCI) on MACCE rates. Fixed, random, and linear mixed models were used to test clinical covariate effects, such as diabetes, lesion characteristics, and procedural factors. Comparing five-year MACCE rates, the pooled odds ratio (OR) between study sites was 0.58 (95% CI: 0.47-0.71), and countries 0.59 (95% CI: 0.45-0.73). By homogeneity testing, no individual site (X2=93.8, p=0.051) or country differences (X2=25.7, p=0.080) were observed. For random effects models, the intraclass correlation was minimal (ICC site=5.1%, ICC country=1.5%, p<0.001), indicating minimal geographical heterogeneity, with a hazard ratio of 0.70 (95% CI: 0.59-0.83). Baseline risk (smoking, diabetes, PAD) did not influence regional five-year MACCE outcomes (ICC 1.3%-5.2%), nor did revascularisation of the left main vs. three-vessel disease (p=0.241), across site or country subgroups. For CABG patients, the number of arterial (p=0.49) or venous (p=0.38) conduits used also made no difference. Conclusions: Geographic variability has no significant treatment effect on MACCE rates at five years. These findings highlight the generalisability of the five-year outcomes of the SYNTAX study.