Prins Kurt W, Duval Sue, Markowitz Jeremy, Pritzker Marc, Thenappan Thenappan
Cardiovascular Division, University of Minnesota Medical School, Minneapolis, MN, USA.
Pulm Circ. 2017 Mar 24;7(1):145-155. doi: 10.1086/690017. eCollection 2017 Mar.
Pulmonary hypertension (PH) complicating chronic obstructive pulmonary disease (COPD-PH) and interstitial lung disease (ILD-PH) (World Health Organization [WHO] Group III PH) increases medical costs and reduces survival. Despite limited data, many clinicians are using pulmonary arterial hypertension (PAH)-specific therapy to treat WHO Group III PH patients. To further investigate the utility of PAH-specific therapy in WHO Group III PH, we performed a systematic review and meta-analysis. Relevant studies from January 2000 through May 2016 were identified in the MEDLINE, EMBASE, and COCHRANE electronic databases and www.clinicaltrials.gov. Change in six-minute walk distance (6MWD) was estimated using random effects meta-analysis techniques. Five randomized controlled trials (RCTs) in COPD-PH (128 placebo or standard treatment and 129 PAH-medication treated patients), two RCTs in ILD-PH (23 placebo and 46 treated patients), and four single-arm clinical trials (50 patients) in ILD-PH were identified. Treatment in both COPD-PH and ILD-PH did not worsen hypoxemia. Symptomatic burden was not consistently reduced but there were trends for reduced pulmonary artery pressures and pulmonary vascular resistance with PAH-specific therapy. As compared to placebo, 6MWD was not significantly improved with PAH-specific therapy in the five COPD-PH RCTs (42.7 m; 95% confidence interval [CI], -1.0 - 86.3). In the four single-arm studies in ILD-PH patients, there was a significant improvement in 6MWD after PAH-specific treatment (46.2 m; 95% CI, 27.9-64.4), but in the two ILD-PH RCTs there was not an improvement (21.6 m; 95% CI, -17.8 - 61.0) in exercise capacity when compared to placebo. Due to the small numbers of patients evaluated and inconsistent beneficial effects, the utility of PAH-specific therapy in WHO Group III PH remains unproven. A future clinical trial that is appropriately powered is needed to definitively determine the efficacy of this widely implemented treatment approach.
慢性阻塞性肺疾病合并肺动脉高压（COPD-PH）和间质性肺疾病合并肺动脉高压（ILD-PH）（世界卫生组织[WHO]第III组肺动脉高压）会增加医疗成本并缩短生存期。尽管数据有限，但许多临床医生正在使用肺动脉高压（PAH）特异性疗法来治疗WHO第III组肺动脉高压患者。为了进一步研究PAH特异性疗法在WHO第III组肺动脉高压中的效用，我们进行了一项系统评价和荟萃分析。在MEDLINE、EMBASE和COCHRANE电子数据库以及www.clinicaltrials.gov中检索了2000年1月至2016年5月的相关研究。使用随机效应荟萃分析技术估计6分钟步行距离（6MWD）的变化。确定了5项COPD-PH的随机对照试验（RCT）（128例接受安慰剂或标准治疗，129例接受PAH药物治疗）、2项ILD-PH的RCT（23例接受安慰剂，46例接受治疗）以及4项ILD-PH的单臂临床试验（50例患者）。COPD-PH和ILD-PH的治疗均未加重低氧血症。症状负担并未持续减轻，但PAH特异性疗法有降低肺动脉压和肺血管阻力的趋势。在5项COPD-PH的RCT中，与安慰剂相比，PAH特异性疗法并未显著改善6MWD（42.7米；95%置信区间[CI]，-1.0 - 86.3）。在4项ILD-PH患者的单臂研究中，PAH特异性治疗后6MWD有显著改善（46.2米；95%CI，27.9 - 64.4），但在2项ILD-PH的RCT中，与安慰剂相比运动能力并未改善（21.6米；95%CI，-17.8 - 61.0）。由于评估的患者数量较少且有益效果不一致，PAH特异性疗法在WHO第III组肺动脉高压中的效用仍未得到证实。需要开展一项有足够样本量的未来临床试验，以明确确定这种广泛应用的治疗方法的疗效。
