Pulmonary Hypertension Research Group, Laval University, Québec City, QC, Canada; Institut Universitaire de Cardiologie et de Pneumologie de Québec Research Center, Laval University, Québec City, QC, Canada.
Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Service de Médecine Interne-Pathologie Vasculaire, and Laboratoire de Biométrie et Biologie Évolutive, Université Claude-Bernard Lyon 1, Lyon, France.
Lancet Respir Med. 2016 Apr;4(4):291-305. doi: 10.1016/S2213-2600(16)00027-8. Epub 2016 Feb 27.
Several randomised controlled studies and a previous meta-analysis have reported conflicting results regarding the effect of combined targeted therapy compared with monotherapy for pulmonary arterial hypertension (PAH). We did a systematic review and meta-analysis to assess the effects of a combination of PAH-specific therapies compared with monotherapy on predefined clinical worsening in PAH.
We searched MEDLINE, Embase, and the Cochrane Library for reports published from Jan 1, 1990, to May 31, 2015, of prospective randomised controlled trials of at least 12 weeks that assessed a combination of PAH-specific therapies (upfront and sequential add-on) compared with background PAH-specific monotherapy in patients older than 12 years. We extracted data from the reports, and assessed the primary outcome of risk of clinical worsening, as defined a priori in each trial, using the Mantel-Haenszel method based on a fixed-effects model.
Of 2017 studies that we identified from our search, we included 17 (4095 patients) in our analysis. 15 studies assessed clinical worsening and were included in the primary analysis. Combined therapy was associated with significant risk reduction for clinical worsening compared with monotherapy (combined therapy 17% [332 of 1940 patients] vs monotherapy 28% [517 of 1862 patients], risk ratio [RR] 0·65 [95% CI 0·58-0·72], p<0·00001). We noted no heterogeneity between the studies (I(2)=18%, phomogeneity=0·25). A publication bias was suggested by the results of an Egger test (t=-2·3982, p=0·031), but when we excluded the four studies with the highest SEs, the RR for clinical worsening was identical (0·65 [95% CI 0·58-0·73], p<0·00001).
In our analysis, combined therapy for PAH was associated with a significant reduction in clinical worsening compared with monotherapy. However, our study was limited by the variable definition of clinical worsening among the trials and possible publication bias. Because many patients still had clinical worsening with combination therapy, identification of innovative therapeutic targets for PAH is thus urgently needed.
None.
几项随机对照研究和一项先前的荟萃分析报告称，肺动脉高压（PAH）的靶向联合治疗与单药治疗相比，疗效存在冲突。我们进行了系统评价和荟萃分析，以评估 PAH 特异性治疗的联合治疗与单药治疗相比，对 PAH 临床恶化的既定临床终点的影响。
我们检索了 MEDLINE、Embase 和 Cochrane 图书馆，以获取 1990 年 1 月 1 日至 2015 年 5 月 31 日期间发表的前瞻性随机对照试验报告，这些报告评估了 PAH 特异性治疗（初始和序贯附加）与年龄大于 12 岁的患者中 PAH 特异性单药治疗相比的疗效。我们从报告中提取数据，并使用固定效应模型的 Mantel-Haenszel 方法，根据每个试验预先定义的标准，评估主要终点临床恶化的风险。
在我们的检索中，有 2017 项研究，我们从中纳入了 17 项（4095 例患者）进行分析。15 项研究评估了临床恶化，并纳入了主要分析。与单药治疗相比，联合治疗显著降低了临床恶化的风险（联合治疗组 17%[1940 例患者中有 332 例] vs 单药治疗组 28%[1862 例患者中有 517 例]，风险比[RR]0.65[95%CI 0.58-0.72]，p<0.00001）。我们没有发现研究之间存在异质性（I(2)=18%，phomogeneity=0.25）。Egger 检验的结果提示存在发表偏倚（t=-2.3982，p=0.031），但当我们排除 SE 最高的四项研究时，临床恶化的 RR 相同（0.65[95%CI 0.58-0.73]，p<0.00001）。
在我们的分析中，与单药治疗相比，PAH 的联合治疗与临床恶化的显著减少相关。然而，我们的研究受到试验中临床恶化定义的差异和可能的发表偏倚的限制。由于许多患者在联合治疗时仍有临床恶化，因此迫切需要确定 PAH 的创新性治疗靶点。
无。
