Campschroer Thijs, Zhu Xiaoye, Vernooij Robin Wm, Lock Mtw Tycho
Department of Urology, Radboud University Nijmegen Medical Center, Geert Grooteplein Zuid 10, Nijmegen, Gelderland, Netherlands, 6525 GA.
Cochrane Database Syst Rev. 2018 Apr 5;4(4):CD008509. doi: 10.1002/14651858.CD008509.pub3.
Ureteral colic is a common reason for patients to seek medical care. Alpha-blockers are commonly used to improve stone passage through so-called medical expulsive therapy (MET), but their effectiveness remains controversial. This is an update of a 2014 Cochrane review; since that time, several large randomised controlled trials (RCTs) have been reported, making this update relevant.
To assess effects of alpha-blockers compared with standard therapy for ureteral stones 1 cm or smaller confirmed by imaging in adult patients presenting with symptoms of ureteral stone disease.
On 18 November 2017, we searched CENTRAL, MEDLINE Ovid, and Embase. We also searched ClinicalTrials.gov and the WHO Portal/ICTRP to identify all published/unpublished and ongoing trials. We checked all references of included and review articles and conference proceedings for articles relevant to this review. We sent letters to investigators to request information about unpublished or incomplete studies.
We included RCTs of ureteral stone passage in adult patients that compared alpha-blockers versus standard therapy.
Two review authors screened studies for inclusion and extracted data using standard methodological procedures. We performed meta-analysis using a random-effects model. Primary outcomes were stone clearance and major adverse events; secondary outcomes were stone expulsion time, number of pain episodes, use of diclofenac, hospitalisation, and surgical intervention. We assessed the quality of evidence on a per-outcome basis using the GRADE approach.
We included 67 studies with 10,509 participants overall. Of these, 15 studies with 5787 participants used a placebo.Stone clearance: Based on the overall analysis, treatment with an alpha-blocker may result in a large increase in stone clearance (risk ratio (RR) 1.45, 95% confidence interval (CI) 1.36 to 1.55; low-quality evidence). A subset of higher-quality, placebo-controlled trials suggest that the likely effect is probably smaller (RR 1.16, 95% CI 1.07 to 1.25; moderate-quality evidence), corresponding to 116 more (95% CI 51 more to 182 more) stone clearances per 1000 participants.Major adverse events: Based on the overall analysis, treatment with an alpha-blocker may have little effect on major adverse events (RR 1.25, 95% CI 0.80 to 1.96; low-quality evidence). A subset of higher-quality, placebo-controlled trials suggest that alpha-blockers likely increase the risk of major adverse events slightly (RR 2.09, 95% CI 1.13 to 3.86), corresponding to 29 more (95% CI 3 more to 75 more) major adverse events per 1000 participants.Patients treated with alpha-blockers may experience shorter stone expulsion times (mean difference (MD) -3.40 days, 95% CI -4.17 to -2.63; low-quality evidence), may use less diclofenac (MD -82.41, 95% CI -122.51 to -42.31; low-quality evidence), and likely require fewer hospitalisations (RR 0.51, 95% CI 0.34 to 0.77; moderate-quality evidence), corresponding to 69 fewer hospitalisations (95% CI 93 fewer to 32 fewer) per 1000 participants. Meanwhile, the need for surgical intervention appears similar (RR 0.74, 95% CI 0.53 to 1.02; low-quality evidence), corresponding to 28 fewer surgical interventions (95% CI 51 fewer to 2 more) per 1000 participants.A predefined subgroup analysis (test for subgroup differences; P = 0.002) suggests that effects of alpha-blockers may vary with stone size, with RR of 1.06 (95% CI 0.98 to 1.15; P = 0.16; I² = 62%) for stones 5 mm or smaller versus 1.45 (95% CI 1.22 to 1.72; P < 0.0001; I² = 59%) for stones larger than 5 mm. We found no evidence suggesting possible subgroup effects based on stone location or alpha-blocker type.
AUTHORS' CONCLUSIONS: For patients with ureteral stones, alpha-blockers likely increase stone clearance but probably also slightly increase the risk of major adverse events. Subgroup analyses suggest that alpha-blockers may be less effective for smaller (5 mm or smaller) than for larger stones (greater than 5 mm).
输尿管绞痛是患者就医的常见原因。α受体阻滞剂常用于通过所谓的药物排石疗法（MET）促进结石排出，但其有效性仍存在争议。这是对2014年Cochrane系统评价的更新；自那时以来，已有多项大型随机对照试验（RCT）发表，因此本次更新具有相关性。
评估α受体阻滞剂与标准治疗相比，对成年输尿管结石病症状患者经影像学证实的1 cm及以下输尿管结石的疗效。
2017年11月18日，我们检索了Cochrane中心对照试验注册库（CENTRAL）、Ovid平台的MEDLINE以及Embase。我们还检索了ClinicalTrials.gov和世界卫生组织国际临床试验注册平台（WHO Portal/ICTRP），以识别所有已发表/未发表及正在进行的试验。我们检查了纳入研究、综述文章及会议论文的所有参考文献，以查找与本综述相关的文章。我们致函研究者，索取未发表或不完整研究的相关信息。
我们纳入了比较α受体阻滞剂与标准治疗的成年输尿管结石排出的随机对照试验。
两名综述作者筛选纳入研究，并使用标准方法程序提取数据。我们采用随机效应模型进行荟萃分析。主要结局为结石清除率和主要不良事件；次要结局为结石排出时间、疼痛发作次数、双氯芬酸的使用、住院情况及手术干预。我们使用GRADE方法按每个结局评估证据质量。
我们共纳入67项研究，总计10509名参与者。其中，15项研究共5787名参与者使用了安慰剂。结石清除率：基于总体分析，使用α受体阻滞剂治疗可能会使结石清除率大幅提高（风险比（RR）1.45，95%置信区间（CI）1.36至1.55；低质量证据）。一部分质量较高的安慰剂对照试验表明，其可能效果可能较小（RR 1.16，95%CI 1.07至1.25；中等质量证据），相当于每1000名参与者中结石清除人数增加116例（95%CI增加51例至182例）。主要不良事件：基于总体分析，使用α受体阻滞剂治疗可能对主要不良事件影响较小（RR 1.25，95%CI 0.80至1.96；低质量证据）。一部分质量较高的安慰剂对照试验表明，α受体阻滞剂可能会使主要不良事件风险略有增加（RR 2.09，95%CI 1.13至3.86），相当于每1000名参与者中主要不良事件增加29例（95%CI增加3例至75例）。接受α受体阻滞剂治疗的患者结石排出时间可能更短（平均差（MD）-3.40天，95%CI -4.17至-2.63；低质量证据），双氯芬酸使用量可能更少（MD -82.41，95%CI -122.51至-42.31；低质量证据），住院次数可能更少（RR 0.51，95%CI 0.34至0.77；中等质量证据），相当于每1000名参与者中住院次数减少69例（95%CI减少93例至32例）。同时，手术干预的需求似乎相似（RR 0.74，95%CI 0.53至1.02；低质量证据），相当于每1000名参与者中手术干预减少28例（95%CI减少51例至增加2例）。一项预定义的亚组分析（亚组差异检验；P = 0.002）表明，α受体阻滞剂的效果可能因结石大小而异，5 mm及以下结石的RR为1.06（95%CI 0.98至1.15；P = 0.16；I² = 62%），而大于5 mm结石的RR为1.45（95%CI 1.22至1.72；P < 0.0001；I² = 59%）。我们未发现基于结石位置或α受体阻滞剂类型可能存在亚组效应的证据。
对于输尿管结石患者，α受体阻滞剂可能会提高结石清除率，但可能也会略微增加主要不良事件的风险。亚组分析表明，α受体阻滞剂对较小（5 mm及以下）结石的效果可能不如对较大结石（大于5 mm）的效果。
