The Role of Phosphodiesterase Inhibitors in Acute Renal Colic: A Systematic Review and Meta-analysis

Introduction: Acute renal colic is a common and intensely painful condition, primarily managed with non-steroidal anti-inflammatory drugs (NSAIDs). However, NSAIDs carry risks of gastrointestinal, renal, and cardiovascular adverse events. Phosphodiesterase (PDE) inhibitors, which promote ureteral smooth muscle relaxation, may offer an alternative for selected patients. This systematic review and meta-analysis assessed the efficacy and safety of PDE inhibitors compared with NSAIDs or placebo in acute renal colic. Methods: PubMed, Embase, Scopus, Web of Science, and Cochrane Library were searched (inception to February 11, 2025) for RCTs comparing PDE inhibitors with NSAIDs or placebo. Study selection, data extraction, and risk of bias (Cochrane RoB 2) were independently performed. Evidence certainty was assessed via GRADE. Meta-analyses were conducted using mean differences (MDs) and odds ratios (ORs) with 95% confidence intervals (CIs) under random-effects models; I² quantified heterogeneity. Results: Six RCTs (1232 participants) were included. PDE inhibitors showed no significant difference in VAS pain intensity versus NSAIDs at 20 minutes (MD: -0.02; 95% CI: -1.34 to 1.30; I² = 84%) or 60 minutes (MD: -0.33; 95% CI: -0.80 to 0.13; I² = 75%), except when combined with NSAIDs, which improved pain relief. PDE inhibitor increased rescue analgesia-free rates compared with NSAID alone, (OR: 3.06; 95% CI: 1.98–4.72; P < 0.001; I² = 0%) while PDE inhibitors were also superior to placebo for avoiding rescue analgesia (OR: 6.42; 95% CI: 3.25–12.68; P < 0.0001; I² = 25%). No overall adverse event difference was found between PDE inhibitors and NSAIDs (OR: 0.87; 95% CI: 0.48–1.60; P = 0.66; I² = 0%).PDE inhibitors had higher adverse events than placebo (OR: 9.30; 95% CI: 3.14–27.53; P < 0.0001; I² = 0%). Evidence certainty ranged from very low to moderate. Conclusion: PDE inhibitors provide analgesic efficacy comparable to NSAIDs as monotherapy and may enhance pain relief when combined with NSAIDs. Larger, high-quality RCTs are warranted to confirm these findings.