Adenosine antagonists for prevention of contrast-induced nephropathy: A meta-analysis of randomized controlled trials with trial sequential analysis

Contrast-induced nephropathy (CIN) is caused by intravascular administration of contrast agent. The efficacy of adenosine antagonists (AAs) in preventing CIN remains controversial, and its elucidation was the objective of the present meta-analysis. A trial sequential analysis (TSA) to assess the reliability of the pooled results was also performed. The Medline, Embase, Web of Science and Cochrane databases were searched to retrieve all published randomized controlled trials (RCTs) comparing AAs with controls in preventing CIN. Heterogeneity, publication bias and quality of studies were assessed. Sensitivity, cumulative and subgroup analyses were also performed. The risk of random errors was evaluated by TSA. A total of 17 trials with 1,483 subjects were included. Pooled results indicated that AAs significantly reduced the incidence of CIN [risk ratio, 0.53; 95% confidence interval (CI), 0.29–0.95; P=0.034] and the serum creatinine (SCr) level after contrast media (CM) administration (standardized mean difference, −0.24; 95% CI, −0.44 to −0.04; P=0.019). Meta-regression did not identify any significant source of heterogeneity. In the subgroup analyses, AAs tended to exhibit a greater prevention efficacy in trials with sample sizes of ≥70, baseline SCr of <1.5 mg/dl and low study quality. TSA on the incidence of CIN indicated that the required information size determined as n=1,778 was not reached, and that the cumulative Z-curve did not cross the TSA boundary. In conclusion, the present meta-analysis of data from current RCTs suggested that AAs reduce the incidence of CIN and the SCr levels after CM administration. However, TSA showed that the risk of having a false-positive result was greater than 5% in the meta-analysis of the incidence of CIN, indicating that more evidence is required to ensure the benefit of AAs in preventing CIN.