Quantifying component effects of tamsulosin 0.4 mg plus tadalafil 5 mg for lower urinary tract symptoms: A systematic review and component network meta-analysis
Sagar Yadav, Aakash Yadav, Shubham Singh Bais, Prasoon Jha, Aarti SharmaABSTRACT
Background:
Combination therapy with an α1-blocker and a phosphodiesterase-5 inhibitor is widely used for benign prostatic hyperplasia (BPH), but the extent to which the benefits of tamsulosin 0.4 mg plus tadalafil 5 mg are additive versus nonadditive remains uncertain.
Materials and Methods:
We systematically reviewed randomized controlled trials comparing tamsulosin 0.4 mg, tadalafil 5 mg, and their fixed combination for BPH. Outcomes assessed were changes in International Prostate Symptom Score (IPSS), Qmax (maximum urinary flow rate), quality of life (QoL), and postvoid residual (PVR). A frequentist random-effects network meta-analysis (NMA) was performed, followed by component NMA (cNMA) using additive and interaction models to quantify component contributions and detect departures from additivity.
Results:
Sixteen trials, including 4854 participants, were analyzed. The combination achieved the greatest symptom reduction in the IPSS network, with a pooled improvement versus placebo of approximately −4.87 IPSS points (95% confidence interval [CI] −6.51 to −3.23). For Qmax, the combination improved flow versus placebo (+1.42 mL/s; 95% CI, 0.49–2.35). For IPSS-QoL, all active regimens improved patient-reported outcomes versus placebo; however, the cNMA interaction term suggested a less-than-additive effect for the combination (interaction estimate −0.55, 95% CI: −0.76 to −0.34), indicating that the QoL gain with combination was smaller than the simple sum of its components. PVR estimates were imprecise, with no consistent differences between the regimens.
Conclusion:
Tamsulosin–tadalafil combination therapy provides the largest overall improvement in lower urinary tract symptoms and urinary flow, whereas QoL benefits appear sub-additive, supporting the need for pragmatic step-up versus upfront combination trials that incorporate adverse events and treatment persistence.