The role of probucol preventing contrast-induced nephropathy in patients undergoing invasive coronary procedures – Systematic review and meta-analysis of randomized controlled trials

OBJECTIVE
The aim of this meta-analysis was to synthesize the latest evidence on the effect of probucol on the incidence of contrast-induced nephropathy (CIN) in patients undergoing coronary angiography (CAG)/percutaneous coronary intervention (PCI).


METHODS
A systematic literature search of PubMed, ScienceDirect, EuropePMC, ProQuest, and Clinicaltrials. gov was performed to retrieve studies that assessed probucol and CIN in CAG/PCI.


RESULTS
Four studies that compared probucol with hydration alone, comprising 1270 subjects, were identified and analyzed. There was no significant difference between probucol and control groups in the baseline level of creatinine and at 48 hours; however, a significant difference was observed at 72 hours (mean difference: -3.87 μmol/L; 95% confidence interval [CI]: -6.58, -1.15; p=0.005). The meta-analysis indicated that probucol did not reduce the CIN incidence (odds ratio [OR]: 0.46; 95% CI: 0.20, 1.08; p=0.08). After performing a leave-one-out sensitivity analysis, removal of a study resulted in a lower risk of CIN (OR: 0.33; 95% CI: 0.19, 0.56; p<0.001). Probucol did not reduce the CIN incidence in a pooled adjusted effect estimate (OR: 0.75; 95% CI: 0.15, 3.87; p=0.73). There was no significant difference in the rate of major adverse events between the 2 groups (OR: 0.39; 95% CI: 0.05, 3.05; p=0.37). Funnel plot results were asymmetrical, indicating possible publication bias. Grading of Recommendations, Assessment, Development and Evaluations qualification demonstrated a low and very low certainty of evidence in unadjusted and adjusted effect estimates, respectively.


CONCLUSION
Probucol did not reduce the incidence of CIN; however, due to the low certainty of evidence, further study is required for a definite conclusion. Although the p value was not significant, the confidence interval showed a nonsignificant trend toward benefit. However, this trend might have been due to publication bias.