Protease inhibitors for preventing complications associated with ERCP: an updated meta-analysis

Background and objectives: The prophylactic use of protease inhibitors in patients undergoing ERCP is still controversial. Our purpose was to evaluate the efficacy of protease inhibitors in preventing ERCP-associated complications.

Design and setting: Meta-analysis; randomized trials that evaluated the efficacy of protease inhibitors were identified.

Patients: A total of 4966 patients were evaluated.

Main outcome measurements: ERCP-associated pancreatitis, hyperamylasemia, abdominal pain, and death.

Results: Eighteen studies (19 cohorts) met the inclusion criteria. Overall results for protease inhibitors showed a significant but small risk reduction in ERCP-associated pancreatitis (pooled risk difference [RD]: -0.029; 95% CI, -0.051 to -0.008 and the number needed to treat, 34.5; 95% CI, 19.6-125). Subgroup analysis in 8 high-quality studies showed a borderline significant efficacy (pooled RD, -0.027; 95% CI, -0.051 to -0.004). Subgroup analysis in 8 gabexate studies did not show significant efficacy (pooled RD, -0.030; 95% CI, -0.062 to 0.003). Subgroup analysis in 5 ulinastatin studies was significant (pooled RD, -0.035; 95% CI, -0.063 to -0.006). Two high-quality studies on ulinastatin yielded nonsignificant results. Analyses for the other outcomes were all nonsignificant. Sensitivity analysis showed that the effect size and level of statistical significance were decreased with increasing study quality.

Conclusions: At present, there is no solid evidence to support the use of protease inhibitors to prevent ERCP-associated complications. Although overall and ulinastatin subgroup analyses showed a small risk reduction for pancreatitis, it seems very possible that low-quality primary studies produced a veneer of efficacy.