Department of Clinical Pharmacology and Epidemiology, Consorzio Mario Negri Sud, Via Nazionale 8, Santa Maria Imbaro, Chieti, Italy.
Am Heart J. 2010 Feb;159(2):245-57. doi: 10.1016/j.ahj.2009.11.028.
In a previous meta-analysis on the approved treatments for pulmonary hypertension, we reported that all therapies caused small changes in 6-minute walk distance over a short period, with minimal effects on hemodynamics and no effect on survival. Since that last review, 10 new clinical trials with about 1,500 patients have been published, which has increased the statistical power of our observations.
A systematic review of all clinical trials in pulmonary arterial hypertension was done.
The pooled effect of all treatments strategies (relative risk [95% CI], P) now shows a significant reduction of 39% (2%-62%, P = .041) in all-cause mortality. The benefits were confined only to patients with advanced disease for 16 weeks, regardless of which class of drug is used. When considering the effects within each drug family, no class of drug produced a statistically significant reduction in all-cause mortality. The improved survival bore no relationship with the change in 6-minute walk, the primary end point in most of the trials.
The impact of vasodilators on long-term survival in pulmonary arterial hypertension remains uncertain. Future trials need to (a) adopt new trial designs that can better address clinical benefits, (b) use new end points that incorporate our best understanding of the disease rather than the ones that are easy to administer, and (c) include longer durations of study and other strategies to clarify if survival is affected.
在之前对肺动脉高压已批准治疗方法的荟萃分析中，我们报告称所有治疗方法在短期内都使 6 分钟步行距离发生微小变化，对血液动力学的影响最小，对生存没有影响。自上次审查以来，又发表了 10 项新的临床试验，涉及约 1500 名患者，这增加了我们观察结果的统计效力。
对所有肺动脉高压临床试验进行了系统回顾。
现在，所有治疗策略的汇总效果（相对风险[95%CI]，P）显示全因死亡率显著降低 39%（2%-62%，P =.041）。这些益处仅局限于使用 16 周的晚期疾病患者，而与使用哪种药物类别无关。当考虑每种药物类别的效果时，没有一种药物类别在全因死亡率方面产生统计学意义上的降低。生存率的提高与大多数试验的主要终点 6 分钟步行距离的变化无关。
血管扩张剂对肺动脉高压的长期生存影响仍不确定。未来的试验需要（a）采用新的试验设计，以更好地解决临床获益问题，（b）使用新的终点，这些终点纳入了我们对疾病的最佳理解，而不是那些易于管理的终点，以及（c）包括更长的研究时间和其他策略，以明确生存是否受到影响。
