Department of Community and Family Medicine, Duke University School of Medicine; Duke Evidence-based Practice Center, Duke Clinical Research Institute, Duke University.
Department of Community and Family Medicine, Duke University School of Medicine.
Chest. 2014 May;145(5):1055-1063. doi: 10.1378/chest.13-1864.
Current treatments for pulmonary arterial hypertension (PAH) have been shown to improve dyspnea, 6-min walk distance (6MWD), and pulmonary hemodynamics, but few studies were designed to compare treatment regimens or assess the impact of treatment on mortality.
We conducted a systematic review to evaluate the comparative effectiveness and safety of monotherapy or combination therapy for PAH using endothelin receptor antagonists, phosphodiesterase inhibitors, or prostanoids. We searched English-language publications of comparative studies that reported intermediate or long-term outcomes associated with drug therapy for PAH. Two investigators abstracted data and rated study quality and applicability.
We identified 28 randomized controlled trials involving 3,613 patients. We found no studies that randomized treatment-naive patients to monotherapy vs combination therapy. There was insufficient statistical power to detect a mortality difference associated with treatment. All drug classes demonstrated increases in 6MWD when compared with placebo, and combination therapy showed improved 6MWD compared with monotherapy. For hospitalization, the OR was lower in patients taking endothelin receptor antagonists or phosphodiesterase-5 inhibitors compared with placebo (OR, 0.34 and 0.48, respectively).
Although no studies were powered to detect a mortality reduction, monotherapy was associated with improved 6MWD and reduced hospitalization rates. Our findings also suggest an improvement in 6MWD when a second drug is added to monotherapy.
目前已证实肺动脉高压（PAH）的治疗方法可以改善呼吸困难、6 分钟步行距离（6MWD）和肺血流动力学，但很少有研究旨在比较治疗方案或评估治疗对死亡率的影响。
我们进行了一项系统评价，以评估内皮素受体拮抗剂、磷酸二酯酶抑制剂或前列腺素类药物单药治疗或联合治疗 PAH 的比较有效性和安全性。我们搜索了英语出版物中关于与 PAH 药物治疗相关的中期或长期结局的比较研究。两名研究者提取数据并评估研究质量和适用性。
我们确定了 28 项随机对照试验，涉及 3613 名患者。我们没有发现将治疗初治患者随机分为单药治疗与联合治疗的研究。由于缺乏统计学效力，无法检测到与治疗相关的死亡率差异。与安慰剂相比，所有药物类别均显示 6MWD 增加，联合治疗显示 6MWD 改善优于单药治疗。对于住院治疗，与安慰剂相比，使用内皮素受体拮抗剂或磷酸二酯酶-5 抑制剂的患者的住院率降低（OR 分别为 0.34 和 0.48）。
尽管没有研究有足够的效力来检测死亡率降低，但单药治疗与改善 6MWD 和降低住院率相关。我们的研究结果还表明，当第二种药物添加到单药治疗中时，6MWD 会有所改善。
