Naftopidil for the treatment of lower urinary tract symptoms compatible with benign prostatic hyperplasia

 

Abstract

Background

Benign prostatic hyperplasia (BPH) is a common condition in aging men causing lower urinary tract symptoms (LUTS). Treatment aims are to relieve symptoms and prevent disease progression. Of the different α-1 adrenergic receptors (ARs) in the prostate, α-1a receptors are known to be central to prostatic smooth-muscle contraction. Recent studies have shown that patients with BPH may also have a predominance of α-1d receptors.

Objectives

To evaluate the efficacy and adverse effects of naftopidil, a selective α-1d oral alpha-blocking agent for the treatment of LUTS associated with BPH.

Search methods

Systematic review of trials published January 1950 to January 2009. Sources included MEDLINE and bibliographies of retrieved articles and review articles.

Selection criteria

Eligible trials included: men diagnosed with symptomatic BPH; compared Naftopidil to placebo, control, or combination therapy; evaluated clinically relevant outcomes between randomized groups; had at least 4-weeks follow up; and were published in English language.

Data collection and analysis

Participant demographics and comorbidities, enrollment criteria, outcomes, adverse events, numbers and reasons for dropouts were extracted onto standardized extraction forms by one reviewer. The mean change and per cent improvement from baseline in AUA (American Urological Association Symptom Score) and IPSS (International Prostate Symptom Score) scores and other efficacy outcomes for treatment and control groups were calculated. If feasible, the efficacy outcomes and adverse events data were pooled.

Main results

Eight trials were eligible (N = 744 participants). All trials were conducted in Japan. Study duration ranged from 4 to 17 weeks. The mean age of participants was 68 years; pretreatment mean IPSS = 17.8 and mean peak urine flow (Qmax) = 9.5 mL/s (milliliters/second).  No trials compared naftopidil to placebo. In 5 trials (N = 419), naftopidil in doses of 25 to 75 mg/d (milligrams/day) showed a mean IPSS improvement similar to low-dose tamsulosin (0.2 mg/d) (8.4 versus 8.9 points). Compared to a phytotherapy preparation (eviprostat), naftopidil significantly improved total IPSS (-5.9 versus 0.4; P < 0.0002). In one trial, the addition of anticholinergic drugs (oxybutynin or propiverine hydrochloride) to naftopidil did not offer any significant improvement for IPSS or Qmax in comparison to treatment with naftopidil alone. Although IPSS did not significantly differ between high- (75 mg/d) and low-dose (25mg/d) naftopidil, high dose significantly improved Qmax compared to low dose (1.2 mL/s versus 0.2 mL/s). Adverse events reported were few, mild and similar to those seen with 0.2 mg/d tamsulosin.

Authors' conclusions

There are no data from placebo controlled trials regarding the efficacy of naftopidil in men with symptomatic BPH. Limited information suggests that treatment with naftopidil provides short-term improvement in urinary symptom-scale scores (total IPSS/AUA), QoL (quality of life) score, and urinary symptoms from baseline comparable to low-dose tamsulosin. Adverse effects due to naftopidil were few and usually mild.

 

Plain language summary

Naftopidil for the treatment of benign prostatic hyperplasia

Benign prostatic hyperplasia (BPH) can cause bothersome lower urinary tract symptoms such as increased frequency, urgency, night-time urinations, straining and hesitancy. BPH is common in older males and its symptoms can affect quality of life. This review of eight trials evaluated naftopidil for the treatment of BPH. Current evidence is sparse. We did not identify any placebo-controlled trials. Naftopidil had a similar short-term efficacy and adverse-effect profile compared to low-dose tamsulosin, and better efficacy than phytotherapy (eviprostat). Adverse effects of naftopidil were few, most commonly dizziness and hypotension. Prior to wide-spread use, more long-term, randomized, controlled studies compared to standard therapy are needed.

 

摘要

背景

Naftopidil用在治療良性前列腺肥大造成的下泌尿道症狀

良性前列腺肥大(BPH)常會造成老年男性的下泌尿道症狀(LUTS)，治療目標是解除症狀並防止疾病惡化。在前列腺不同的α −1腎上腺激素性受體(ARs)中，α −1a受體被認為是主要控制前列腺的平滑肌收縮。最近的研究指出，患有良性前列腺肥大(BPH)的病人也同樣擁有大量的α −1d受體。

目標

評估naftopidil的治療效益及副作用，naftopidil是一種α −1d選擇性的口服甲型阻斷劑，用來治療良性前列腺肥大(BPH)相關的下泌尿道症狀(LUTS)。

搜尋策略

系統性的回顧發表自1950年1月至2009年1月的臨床試驗，資料來源包括MEDLINE及用以回顧的原創文章及回顧性文章的參考書目。

選擇標準

納入回顧的試驗必須要是有診斷為有症狀的良性前列腺肥大(BPH)男性；比較Naftopidil及安慰劑對照的臨床試驗或併用療法；在隨機的組別間評估臨床相關的結果；至少追蹤四周；用英文發表之試驗。

資料收集與分析

由單一專家來統計受試者的人口統計學資料、合併的併發症、納入的條件、結果、副作用、退出試驗的人數及原因。對於AUA評分(美國泌尿科協會症狀評分表) and IPSS評分(國際前列腺症狀評分表)，其他藥物的治療效果，及對照組的平均變化及改善的百分比，也會統計計算。若可以的話，對於治療效果及副作用資料也會ㄧ併納入統計。

主要結論

共有8個符合條件的臨床試驗(N = 744)，所有臨床試驗皆由日本主導完成，試驗研究時間從4周到17周，平均受試者年齡為68歲，治療前的平均IPSS為17.8分，平均最大尿流速(Qmax)為9.5毫升/秒(mL/s)，沒有臨床比較naftopidil及安慰劑。在五個臨床試驗中，在每天使用naftopidil劑量為25到75毫克的病患，與每天使用低劑量tamsulosin (0.2 mg/d)的病患比較，平均IPSS的進步是差不多的(8.4 分比8.9 分) 。與草本藥物治療比較(eviprostat)，在IPSS總分上，naftopidil有明顯的進步(−5.9分比上0.4; P < 0.0002). naftopidil加上抗膽鹼激素藥物(oxybutynin或propiverine hydrochloride)的臨床試驗顯示，額外加上的藥物無法在IPSS或 Qmax上得到明顯的改善。雖然高劑量(75 mg/d)及低劑量(25 mg/d)naftopidil在IPSS上的改善沒有明顯差異，但在Qmax上高劑量(75 mg/d)比起低劑量(25 mg/d)naftopidil有顯著地改善。目前所知的藥物副作用則非常少，輕微的副作用，或是跟0.2 mg/d tamsulosin一樣的副作用。

作者結論

naftopidil在有症狀的前列腺肥大男性的治療，目前仍沒有安慰劑控制的臨床試驗顯示效益。對於naftopidil的治療有限的資料顯示，在泌尿道症狀評分 (IPSS/AUA總分) 上、QoL (生活品質)評分上、比較於低劑量的tamsulosin泌尿道症狀的改善上，會有短暫的改善。naftopidil的副作用非常地少，而且通常輕微。

翻譯人

本摘要由臺灣大學附設醫院洪順發翻譯。

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

前列腺肥大會造成令人困擾的下泌尿道症狀，像是增加排尿頻率、尿急感、夜尿、排尿用力及排尿前等待開始排尿的時間延長。BPH常見於年長男性，而且症狀會影響他們的生活品質。本篇檢閱8個臨床試驗的結果，評估naftopidil用在BPH上的治療效果. 目前的證據仍很微薄，也沒有安慰劑控制的臨床試驗。Naftopidil跟低劑量的tamsulosinㄧ樣，比草本治療(eviprostat)好，會有短暫的治療效果及相似的副作用。Naftopidil的副作用很少，最常見的是頭暈及低血壓。在廣泛地運用在治療前，需要有更長期、隨機、有對照組控制的臨床研究。