Impact of cardiovascular risk factors and related comorbid conditions and medical therapy reported at baseline on the treatment response to tadalafil 5 mg once-daily in men with lower urinary tract symptoms associated with benign prostatic hyperplasia: an integrated analysis of four randomised, double-blind, placebo-controlled, clinical trials

Int J Clin Pract. 2015 Dec;69(12):1496-507. doi: 10.1111/ijcp.12722. Epub 2015 Aug 24.


Purpose: The influence of cardiovascular risk factors/comorbidities on response to oral once-daily tadalafil 5 mg was explored in men with lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH).

Methods: This post hoc analysis pooled data from four double-blind studies in which 1498 men with > 6-mo history of LUTS/BPH were randomised and received either once-daily placebo (n = 746) or tadalafil 5 mg (n = 752) for 12 weeks. Descriptive statistics were reported for changes in total International Prostate Symptom Score (IPSS), IPSS voiding and storage subscores, and IPSS quality-of-life (QoL) index. Treatment group differences by baseline clinical and cardiovascular factors and medical therapies were examined using analysis of covariance.

Results: Tadalafil was effective in men with LUTS/BPH and cardiovascular risk factors/comorbidities except for patients receiving > 1 antihypertensive medication. Placebo-adjusted least squares (LS) mean improvements in total IPSS were -1.2 (95% CI: -2.5 to -0.0) in men taking > 1 antihypertensive medication vs. -3.3 (95% CI: -4.4 to -2.1) in men taking one medication (interaction p = 0.020). In addition, placebo-adjusted LS mean improvements in total IPSS were -0.2 (95% CI, -2.1 to 1.7) in men who reported use of diuretics vs. -2.8 (95% CI, -3.7 to -1.9) in men who reported taking other antihypertensive medications vs. -2.3 (95% CI, -3.2 to -1.5) in men who reported not using any antihypertensive drug (p-value for interaction = 0.053).

Conclusions: Once-daily tadalafil 5 mg improved LUTS/BPH, regardless of severity, in men with coexisting cardiovascular risk factors/comorbidities, except for patients with history of > 1 drug for arterial hypertension. Use of diuretics may contribute to patients' perception of a negated efficacy of tadalafil on LUTS/BPH. Comorbidities should be considered when choosing the optimal medicine to treat men with LUTS/BPH.

Trial registration: NCT00384930 NCT00827242 NCT00855582 NCT00970632.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cardiovascular Diseases / complications*
  • Comorbidity
  • Double-Blind Method
  • Drug Administration Schedule
  • Humans
  • Lower Urinary Tract Symptoms / drug therapy*
  • Male
  • Middle Aged
  • Phosphodiesterase 5 Inhibitors / administration & dosage*
  • Prostatic Hyperplasia / drug therapy*
  • Risk Factors
  • Tadalafil / administration & dosage*
  • Vasodilator Agents / administration & dosage*


  • Phosphodiesterase 5 Inhibitors
  • Vasodilator Agents
  • Tadalafil

Associated data