Does treatment response to ambrisentan vary by pulmonary arterial hypertension severity? Implications for clinicians and for the design of future clinical trials.
Does treatment response to ambrisentan vary by pulmonary arterial hypertension severity? Implications for clinicians and for the design of future clinical trials.
复制标题
DOI：
10.1111/ijcp.12331
复制
发表时间：
2014-05
影响因子：
2.6
通讯作者：
Torres F
中科院分区：
文献类型：
--
作者：
Chin KM;Bartolome S;Miller K;Blair C;Gillies H;Torres F
最近的肺动脉高压临床试验纳入了世界卫生组织（WHO）功能等级为I-II的患者。然而，基线功能等级和其他严重程度对结果的影响尚未得到详细评估。根据功能等级、血流动力学、BNP水平和6分钟步行距离（6MWD）分组的患者在ARIES-1和aries - 2关键试验中的结果进行评估，ambrisentan是一种每日一次的口服内皮素-1拮抗剂。ARIES-E扩展研究的长期结果也进行了评估。在12周时，与安慰剂相比，ambrisentan治疗的早期和晚期功能级患者在6MWD方面表现出相似的改善。然而，疾病更严重的患者在按其他严重程度分组后，其6MWD的改善程度更大。这包括更高的基线BNP水平，更短的基线6MWD和更严重的基线血流动力学（BNP p<0.05，其他比较p=NS，作为相互作用项进行分析）。在长期开放标签随访期间，在基线时功能等级为III/IV的患者，维持6MWD改善、免于临床恶化和生存的数值也更差。在12周的临床试验和长期随访中，较轻和较严重的PAH患者均受益于ambrisentan治疗与安慰剂，但对于BNP水平较高的患者，与安慰剂相比，改善更大。
Recent clinical trials in pulmonary arterial hypertension have included World Health Organization (WHO) functional classes I–II patients. However, the impact of baseline functional class and other measures of severity on outcomes has not been evaluated in detail. Outcomes at 12-weeks for patients grouped by functional class, hemodynamics, BNP level and six minute walk distance (6MWD) were evaluated for patients in the ARIES-1 and 2 pivotal trials of ambrisentan, a once daily oral endothelin-1 antagonist. Long-term outcomes in the ARIES-E extension study were also evaluated. At 12-weeks, ambrisentan treated patients with both early and late functional class showed similar improvement in 6MWD relative to placebo. However, patients with more severe disease tended to have greater improvement in 6MWD after grouping by other measures of severity. This included higher baseline BNP level, shorter baseline 6MWD and more severe baseline hemodynamics (p<0.05 for BNP and p=NS for other comparisons, analyzed as interaction terms). During long-term open label follow-up, maintenance of 6MWD improvement, freedom from clinical worsening and survival were also numerically worse for patients who were functional class III/IV at baseline. Patients with both less severe and more severe PAH benefited from ambrisentan therapy vs. placebo in 12-week clinical trials and during long-term follow-up, but greater improvement vs. placebo was seen for those with higher BNP levels.
登录
查看更多内容
影响因子：
158.5
作者：
Galiè, N;Ghofrani, HA;Simonneau, G
通讯作者：
Simonneau, G
影响因子：
8.9
作者：
Barst, Robyn J.;Oudiz, Ronald J.;Galie, Nazzareno
通讯作者：
Galie, Nazzareno
影响因子：
158.5
作者：
Olschewski, H;Simonneau, G;Seeger, W
通讯作者：
Seeger, W
影响因子：
158.5
作者：
Rubin, LJ;Badesch, DB;Simonneau, G
通讯作者：
Simonneau, G
影响因子：
24
作者：
Oudiz, Ronald J.;Galie, Nazzareno;Rubin, Lewis J.
通讯作者：
Rubin, Lewis J.