Pulmonary Hypertension Research Group, Quebec City, QC, Canada; Institut universitaire de cardiologie et de pneumologie de Québec Research Center, Laval University, Quebec City, QC, Canada.
Department of Internal and Vascular Medicine, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, 165, Chemin du Grand-Revoyet, Pierre-Bénite cedex, France; UMR 5558, Laboratoire de Biométrie et Biologie Évolutive, CNRS, Université Lyon 1, Université Claude-Bernard Lyon 1, Lyon, France.
Chest. 2018 May;153(5):1142-1152. doi: 10.1016/j.chest.2017.11.014. Epub 2017 Nov 23.
Relative risk (RR) and number needed-to-treat (NNT) are frequently time-dependant measures. We performed a systematic review and meta-analysis to assess whether trial duration influenced the relative and absolute risk of worsening in randomized controlled trials (RCTs) comparing combination therapy (CT) of pulmonary arterial hypertension (PAH)-specific therapies vs monotherapy (MT).
We searched MEDLINE, Embase, and the Cochrane Library (January 1990 to September 2016) for RCTs assessing CT compared with MT in PAH. The primary outcome was the risk of clinical worsening. We assessed whether trial duration correlated with RR and NNT using weighted meta-regression with mixed effects. Changes in NNT overtime were also assessed using data from long-term event-driven trials.
There were 3,801 patients throughout 15 studies included. The RR for clinical worsening positively correlated with trial duration (R = 0.67, P = .0002), whereas the NNT did not (mean NNT, 7; R = 0.02; P = .65). Among long-term event-driven trials, the mean NNT progressively decreased until 52 weeks of follow-up, being stable thereafter. Conversely, the mean RR progressively increased from approximately 0.40 at week 16 to approximately 0.68 at week 104.
Absolute risk reduction of clinical worsening was relatively constant beyond 6 to 12 months of treatment in clinical trials comparing CT with MT in PAH. These results question the need for CT trials of very long duration in PAH.
相对风险（RR）和需要治疗的人数（NNT）是经常依赖时间的指标。我们进行了系统评价和荟萃分析，以评估试验持续时间是否会影响比较肺动脉高压（PAH）特异性治疗联合治疗（CT）与单一治疗（MT）的随机对照试验（RCT）中恶化的相对和绝对风险。
我们检索了 MEDLINE、Embase 和 Cochrane 图书馆（1990 年 1 月至 2016 年 9 月），以评估 CT 与 MT 在 PAH 中的比较。主要结局是临床恶化的风险。我们使用混合效应加权荟萃回归评估了试验持续时间与 RR 和 NNT 的相关性。还使用长期事件驱动试验的数据评估了 NNT 随时间的变化。
在 15 项研究中共有 3801 例患者。临床恶化的 RR 与试验持续时间呈正相关（R = 0.67，P =.0002），而 NNT 则没有（平均 NNT，7；R = 0.02；P =.65）。在长期事件驱动的试验中，平均 NNT 逐渐下降，直到随访 52 周，此后保持稳定。相反，平均 RR 从大约 16 周的 0.40 逐渐增加到大约 104 周的 0.68。
在 PAH 中比较 CT 与 MT 的临床试验中，治疗 6 至 12 个月后，临床恶化的绝对风险降低相对稳定。这些结果对 PAH 中非常长试验持续时间的 CT 试验的必要性提出了质疑。
