Prognostic value of total bilirubin level for patients suffering from coronary heart disease undergoing percutaneous coronary intervention: a meta-analysis

The objective of this study is to explore the prognostic value of serum total bilirubin for major adverse cardiovascular events (MACE), cardiovascular death (CV death), and all-cause mortality in coronary heart disease (CHD) patients after percutaneous coronary intervention (PCI).

Databases (PubMed, Cochrane Library, Embase, Web of Science) were searched up to May 2026). Studies were screened via PICOS. Two researchers independently extracted data and assessed study quality using Newcastle-Ottawa Scale. Meta-analysis was performed using STATA 16.0. Subgroup analysis was performed to explore the source of heterogeneity, and Egger's test was conducted to examine publication bias.

In total, 17 observational studies involving 27,580 patients with CHD undergoing PCI were included. Methodological quality was generally high (NOS score ≥7). The primary analyses were performed with a priori stratification by follow-up setting. In the long-term follow-up subgroup (12 studies), although a high total bilirubin level was significantly associated with a lowered risk of MACEs (pooled OR = 0.65, 95% CI 0.46-0.92, P = 0.016), substantial heterogeneity was observed within the subgroup (I² = 86.5%). A significant protective effect was also noted for all-cause mortality (7 studies; OR = 0.59, 95% CI 0.39-0.89, P = 0.011), with moderate heterogeneity (I² = 53.6%). For CV death (9 studies), no statistical significance was reached (OR = 0.71, 95% CI 0.43-1.18, P = 0.187). In the in-hospital acute-phase subgroup, high bilirubin was associated with a significantly increased risk of MACEs (5 studies; OR = 2.33, 95% CI 1.72-3.15, P < 0.001), with low heterogeneity (I² = 23.6%). An elevated risk was also noted for CV death (2 studies; OR = 2.79, 95% CI 1.28-6.08, P = 0.010). For all-cause mortality (3 studies), the pooled OR was 2.33, but did not reach statistical significance (P = 0.084). Between-subgroup heterogeneity tests indicated statistically significant differences in effects (all P < 0.01). Further analyses within the long-term follow-up subgroup revealed more pronounced protective effects among older patients (> 65 years), mixed CAD cohorts, and those with a > 70% male proportion. Studies not excluding liver disease showed more robust protective effects, though very few in number. Dose-response analysis showed that no linear or nonlinear association was observed (OR = 0.969, 95% CI 0.919-1.022, P = 0.252). Sensitivity analysis based on the leave-one-out method revealed robust pooled results. Begg's test and Egger's test demonstrated that no significant publication bias was detected (all P > 0.05).

Serum total bilirubin shows a context-dependent bidirectional association with adverse outcomes in patients with CHD after PCI, but does not demonstrate a consistent independent prognostic value. The apparent protective effect observed in long-term follow-up, older, or stable CHD populations and the risk-elevating effect in the in-hospital acute phase are exploratory findings that require further validation. Given the extremely high heterogeneity (mainly due to inconsistencies in MACE endpoint definitions, liver disease exclusion criteria, and CHD subtype classifications) and the negative dose-response analysis (likely underpowered), current evidence does not support total bilirubin as a robust or generalizable prognostic biomarker. Future prospective studies with standardized designs are needed to elucidate its potential clinical utility.

https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=1067176, identifier CRD420251067176.