Model-based meta-analysis of the time to first acute urinary retention or benign prostatic hyperplasia-related surgery in patients with moderate or severe symptoms

Salvatore D'Agate, Chandrashekhar Chavan, Michael Manyak, Juan Manuel Palacios-Moreno, Matthias Oelke, Martin C. Michel, Claus G. Roehrborn, Oscar Della Pasqua

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Aims: Combination therapy of 5α-reductase inhibitor and α-blocker is a guideline-endorsed therapeutic approach for patients with moderate-to-severe lower urinary tract symptoms or benign prostatic hyperplasia (LUTS/BPH) who are at risk of disease progression. We aimed to disentangle the contribution of clinical and demographic baseline characteristics affecting the risk of acute urinary retention or BPH-related surgery (AUR/S) from the effect of treatment with drugs showing symptomatic and disease-modifying properties. Methods: A time-to-event model was developed using pooled data from patients (n = 10 238) enrolled into six clinical studies receiving placebo, tamsulosin, dutasteride or tamsulosin-dutasteride combination therapy. A parametric hazard function was used to describe the time to first AUR/S. Covariate model building included the assessment of relevant clinical and demographic factors on baseline hazard. Predictive performance was evaluated by graphical and statistical methods. Results: An exponential hazard model best described the time to first AUR/S in this group of patients. Baseline International Prostate Symptom Score, prostate-specific antigen, prostate volume and maximum urine flow were identified as covariates with hazard ratio estimates of 1.04, 1.08, 1.01 and 0.91, respectively. Dutasteride monotherapy and tamsulosin-dutasteride combination therapy resulted in a significant reduction in the baseline hazard (56.8% and 66.4%, respectively). By contrast, the effect of tamsulosin did not differ from placebo. Conclusions: Our analysis showed the implications of disease-modifying properties of dutasteride and tamsulosin-dutasteride combination therapy for the risk of AUR/S. It also elucidated the contribution of different baseline characteristics to the risk of these events. The use of tamsulosin monotherapy (symptomatic treatment) has no impact on individual long-term risk.

Original languageEnglish (US)
Pages (from-to)2777-2789
Number of pages13
JournalBritish Journal of Clinical Pharmacology
Issue number7
StatePublished - Jul 2021


  • acute urinary retention
  • baseline risk factors
  • benign prostatic hyperplasia
  • disease-modifying properties
  • dutasteride
  • lower urinary tract symptoms
  • tamsulosin
  • time-to-event modelling

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)


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