他达拉非5 mg治疗前列腺增生继发下尿路症状的荟萃分析

目的评价他达拉非(tadalafil)5 mg治疗前列腺增生继发下尿路症状(BPH/LUTS)的疗效及安全性。方法计算机及手工检索相关的随机对照研究(RCTs)。计算机检索时间限定为数据库建立至2018年10月,数据库包括万方数据库、中国期刊全文数据库(CNKI)、中国科技期刊数据库(VIP)、中国生物医学文献数据库(CBM),EMBASE、PubMed、Cochrane Library、Clinicaltrials.gov。对符合纳入标准的研究进行质量评估,提取数据并使用RevMan 5.3软件进行荟萃分析。结果本次分析纳入9个RCTs,共计3501例患者,其中他达拉非5 mg组1758例,安慰剂对照组1743例。与安慰剂组相比,他达拉非5 mg组可降低国际前列腺症状评分(IPSS)[MD=-1.79,95%CI(-2.19,-1.39)],改善生活质量(IPSS-Qol)[MD=-0.26,95%CI(-0.36,-0.16)],但对最大尿流率(Qmax)没有明显改善[MD=0.15,95%CI(-0.35,0.64),P=0.55]。与安慰剂组相比,他达拉非5 mg组不会明显增加因不良事件而退出的患者比例[RR=1.54,95%CI(0.96,2.49),P=0.08,I 2=0%]。结论他达拉非5 mg治疗前列腺增生可改善患者的下尿路症状,并具有良好的耐受性。     

Efficacy and tolerability of doxazosin gastro-intestinal therapeutic system versus tamsulosin in patients with lower urinary tract symptoms associated with benign prostatic hyperplasia: A systematic review and meta-analysis

Background:Alpha1-adrenoceptor antagonists (α₁-blockers) are first-line drugs for the treatment of lower urinary tract symptoms associated with benign prostate hyperplasia (BPH). Doxazosin gastrointestinal therapeutic system (GITS) and tamsulosin belong to the 2 most frequently prescribed α₁-blockers. This systematic review and meta-analysis was performed to compare the efficacy and tolerability of these 2 α₁-blockers.Methods:A systematic review of published randomized controlled trials in English or Chinese language was performed using the PubMed, EMBASE, Cochrane Library, CNKI, Wanfang, and Vip databases. After data extraction and quality assessment, the meta-analysis was performed to compare clinical parameters (International Prostate Symptom Score [IPSS] total [IPSS-T], storage [IPSS-S], voiding [IPSS-V], maximum urine flow [Q_max], and postvoid residual) and adverse events (AEs) that changed after first drug intake.Results:After the screening, 8 eligible randomized controlled trials with 1316 patients were identified. Doxazosin-GITS showed a significantly higher efficacy compared with tamsulosin (IPSS-T P < .001, IPSS-S P < .001, and IPSS-V P < .001). There were no significant differences between the 2 drugs for changes in Q_max (P = .477) or postvoid residual (P = .739). The overall AEs were significantly lower in the doxazosin-GITS group (risk ratio: 0.77; 95% CI: 0.54–1.08; P = .036). However, dizziness (P = .387), headache (P = .745), asthenia (P = .693), postural hypotension (P = .114), and retrograde ejaculation (P = .187) were similar between the 2 groups.Conclusions:This meta-analysis indicates that doxazosin-GITS has significantly higher efficacy and lower AEs than tamsulosin in patients with lower urinary tract symptoms/benign prostate hyperplasia.     

Tadalafil for the Treatment of Lower Urinary Tract Symptoms in Japanese Men with Benign Prostatic Hyperplasia: Results from a 12‐week Placebo‐controlled Dose‐finding Study with a 42‐week Open‐label Extension

Objectives: To examine the efficacy, safety, and dose response of tadalafil once daily in Japanese men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (BPH‐LUTS). Methods: Men ≥45 years with moderate‐to‐severe BPH‐LUTS were randomized to once‐daily placebo (N = 140), tadalafil 2.5 mg (N = 142), or tadalafil 5.0 mg (N = 140), in a 12‐week double‐blind phase, followed by a 42‐week, tadalafil 5.0 mg open‐label extension (OLE) phase (N = 394). The primary outcome was total International Prostate Symptom Score (IPSS) change from baseline to last available observation in the double‐blind phase. Results: The least squares (LS) mean difference between placebo and tadalafil in total IPSS change from baseline was ?0.7 (P = 0.201) and ?1.1 (P = 0.062) for tadalafil 2.5 and 5 mg, respectively (ANCOVA; a dose‐dependent improvement in placebo‐adjusted total IPSS for tadalafil 5 mg versus 2.5 mg of 57%). Repeated‐measures analyses identified a significant total IPSS change for tadalafil 5 mg (LS mean difference between placebo and tadalafil 5 mg: ?1.2; P = 0.035), but not tadalafil 2.5 mg, at week 12. Significant improvements for tadalafil 5 mg were demonstrated (ANCOVA) for IPSS obstructive subscore (P = 0.033) and IPSS quality of life index (P = 0.022). Numerical improvements in IPSS scores were maintained over the OLE phase. Tadalafil was well tolerated with no unexpected adverse events. Conclusion: Tadalafil (5.0 mg) had a favorable benefit‐to‐risk profile, supporting further investigation of tadalafil (5.0 mg) in Japanese men with BPH‐LUTS.