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Efficacy and safety of ambrisentan in Chinese patients with connective tissue disease-pulmonary arterial hypertension: a post-hoc analysis.

ABSTRACT: BACKGROUND:The efficacy and safety of ambrisentan has been previously evaluated in Chinese patients with pulmonary arterial hypertension (PAH). This post-hoc analysis assessed the efficacy and safety of ambrisentan in a subgroup of connective tissue disease (CTD) patients with PAH. METHODS:In this open-label, single-arm study, patients received ambrisentan 5?mg once daily for 12?weeks, followed by 12-week dose titration period (dose up to 10?mg). Efficacy endpoints included change from baseline in exercise capacity (measured by 6-min walk test [6MWT]), N-terminal pro B type natriuretic peptide (NT-proBNP) plasma levels, WHO Functional Class (FC) and Borg Dyspnoea Index (BDI) scores from baseline to weeks 12 and 24. Safety endpoints included time to clinical worsening and incidence of adverse events (AEs). RESULTS:In total, 71 Chinese patients with CTD-PAH were included in this analysis. Ambrisentan treatment significantly improved exercise capacity (6MWT) from baseline (mean: 366.4?m) to week 12 (63.8?m, p?

SUBMITTER: Li M

PROVIDER: S-EPMC7367256 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Efficacy and safety of ambrisentan in Chinese patients with connective tissue disease-pulmonary arterial hypertension: a post-hoc analysis.

Li Mengtao M Jing Zhi-Cheng ZC Li Yang Y Huo Yong Y Yu Zaixin Z Zhang Gangcheng G Zhu Ping P Liu Jinming J Ji Qiushang Q Wu Bingxiang B Zhong Jinhua J Wang Pingping P Zhu Wenjing W Zeng Xiaofeng X

BMC cardiovascular disorders 20200717 1

<h4>Background</h4>The efficacy and safety of ambrisentan has been previously evaluated in Chinese patients with pulmonary arterial hypertension (PAH). This post-hoc analysis assessed the efficacy and safety of ambrisentan in a subgroup of connective tissue disease (CTD) patients with PAH.<h4>Methods</h4>In this open-label, single-arm study, patients received ambrisentan 5 mg once daily for 12 weeks, followed by 12-week dose titration period (dose up to 10 mg). Efficacy endpoints included change ...[more]

PMID: 32680480

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Project description:BackgroundAlthough several new drugs have been approved in recent years, pulmonary arterial hypertension (PAH) remains a rapidly progressive disease with a poor prognosis. Ambrisentan, a selective endothelin type A antagonist, has been approved for treatment of PAH. This open label study assessed the efficacy and safety of ambrisentan in Chinese subjects with PAH.MethodsEligible patients with PAH (World Health Organisation [WHO] functional class [FC] II orIII) were enrolled and received Ambrisentan (5 mg) once daily for a 12-week preliminary evaluation period, and a 12-week dose-adjustment period (dose titration to 10 mgallowed). Endpoints included: change from baseline in 6-Minute Walk Distance (6-MWD), N-Terminal Pro B-Type Natriuretic Peptide (NT-pro-BNP), WHO FC, Borg Dyspnoea Index (BDI), clinical worsening of PAH and incidences of adverse events (AE).ResultsOne hundred thirty-three subjects (85 % women, mean age: 36 years) with PAH (WHOFC II or III) were enrolled and received ambrisentan (5 mg) once daily for a 12-week preliminary evaluation period, and a 12-week dose-adjustment period. Mean (SD) duration of drug exposure was 161.7 (27.13) days. Ambrisentan (average daily dose of 6.27 mg) significantly improved exercise capacity (6MWD) from baseline (mean: 377.1 m [m]) at week 12 (+53.6 m, p < 0.001) (primary endpoint). Improvement in exercise capacity was noted as early as week 4, and was sustained up to week 24 (+ 64.4 m, p < 0.001). NT-pro-BNP plasma levels decreased significantly (p < 0.001) at week 12 (-861.4 ng/L) and week 24 (-806 ng/L) from baseline (mean: 1600.7 ng/L). The WHO FC showed improvements for 44 subjects at week 12 and 51 subjects at week 24. BDI scores decreased significantly at week 12 (-0.3, p < 0.001) and week 24 (-0.2, p = 0.003) from baseline (mean: 2.5). Four patients died during the study (sudden cardiac death [n = 2], cerebral haemorrhage [n = 1], cardiac failure [n = 1]). Drug related adverse events occurred in 34.3 % of subjects; peripheral oedema (11.2 %) and flushing (8.2 %) occurred most frequently.ConclusionAmbrisentan (5 and 10 mg, orally) significantly improved the exercise capacity in Chinese PAH subjects with a safety profile similar to that observed in global studies.Trial registrationNCT No. (ClinicalTrials.gov): NCT01808313 ; Registration date (first time): February 28, 2013.

Project description:ObjectivesFew studies have focused on pulmonary arterial hypertension (PAH) associated with connective tissue diseases (CTDs). The optimal treatment for CTD-PAH has yet to be established.DesignMeta-analysis of the data from evaluations of treatment for PAH generally (19 studies) and CTD-PAH specifically (nine studies) to compare the effects of pulmonary vasodilative PAH agents. MEDLINE, EMBASE and BIOSIS were searched. English-language full-text articles published between January 1990 and August 2012 were eligible.SettingInternational.ParticipantsPatients with PAH generally (n=3073) and CTD-PAH specifically (n=678).Primary outcome measureExercise capacity (6 min walk distance, 6 MWD).ResultsPatients with PAH (all forms) had mean age 32-55 years (women, 61-87%); CTD-PAH patients had mean age 45-55 years (women, 74-95%). Overall estimate of mean change in 6 MWD from baseline (95% CI) for the active treatment group versus the control group in all patients with PAH was 34.6 m (27.4-41.9 m). Pooled mean differences from the results for patients receiving placebo by subgroup of patients receiving phosphodiesterase (PDE)-5 inhibitors, endothelin receptor antagonists (ERAs) and prostacyclin (PGI2) analogues were 22.4-45.5, 39.5-44.2 and 12.4-64.9 m, respectively. Overall estimate of mean difference between changes in 6 MWD in patients with CTD-PAH was 34.2 m (23.3-45.0 m). Pooled mean differences by subgroup of patients receiving PDE-5 inhibitors, ERAs and PGI2 analogues in patients with CTD-PAH were 37.0-47.1, 14.1-21.7 and 21.0-108.0 m, respectively. ERAs were less effective in patients with CTD-PAH than all-form patients with PAH: 14.1 m (-4.4-32.6 m) vs 39.5 m (19.5-59.6 m) for bosentan and 21.7 m (2.2-41.3 m) vs 44.2 m (30.2-58.2 m) for ambrisentan.ConclusionsAll three types of PAH agent are effective. However, ERAs may be a less effective choice against CTD-PAH; further studies are needed. Limitations include the limited number of studies for some agents and for patients with CTD-PAH.

Dataset Information

Efficacy and safety of ambrisentan in Chinese patients with connective tissue disease-pulmonary arterial hypertension: a post-hoc analysis.

Publications

Efficacy and safety of ambrisentan in Chinese patients with connective tissue disease-pulmonary arterial hypertension: a post-hoc analysis.

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