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

BMC Cardiovasc Disord. 2020 Jul 17;20(1):339. doi: 10.1186/s12872-020-01591-1.

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 < 0.001) and week 24 (73.2 m, p < 0.001). A significant reduction in NT-proBNP levels was observed from baseline (mean: 1837.5 ng/L) to week 12 (- 1156.8 ng/L, p < 0.001) and week 24 (- 1095.5 ng/L, p < 0.001). BDI scores decreased significantly at week 12 (- 0.6, p < 0.001) and week 24 (- 0.4, p = 0.002) from baseline (mean: 2.7). The WHO FC improved in 29 (40.8%) and 34 (47.9%) patients at weeks 12 and 24, respectively. Adverse events were reported in 52 (73.2%) patients. One patient (1.4%) experienced clinical worsening at week 24.

Conclusion: Ambrisentan showed significant improvement in exercise capacity and no clinical worsening in the majority of Chinese patients with CTD-PAH in the 24-week treatment period. The AEs observed in the CTD-PAH subgroup were consistent with the known safety profile of ambrisentan in the overall Chinese PAH population.

Trial registration: ClinicalTrial.gov Identifier, https://clinicaltrials.gov/, NCT01808313 Registration date (first time): February 28, 2013.

Keywords: Ambrisentan; Chinese; Exercise capacity.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antihypertensive Agents / adverse effects
  • Antihypertensive Agents / therapeutic use*
  • Beijing
  • Biomarkers / blood
  • Connective Tissue Diseases / complications*
  • Connective Tissue Diseases / diagnosis
  • Endothelin A Receptor Antagonists / adverse effects
  • Endothelin A Receptor Antagonists / therapeutic use*
  • Exercise Tolerance / drug effects
  • Female
  • Humans
  • Male
  • Middle Aged
  • Natriuretic Peptide, Brain / blood
  • Peptide Fragments / blood
  • Phenylpropionates / adverse effects
  • Phenylpropionates / therapeutic use*
  • Pulmonary Arterial Hypertension / diagnosis
  • Pulmonary Arterial Hypertension / drug therapy*
  • Pulmonary Arterial Hypertension / etiology*
  • Pulmonary Arterial Hypertension / physiopathology
  • Pyridazines / adverse effects
  • Pyridazines / therapeutic use*
  • Recovery of Function
  • Time Factors
  • Treatment Outcome
  • Young Adult

Substances

  • Antihypertensive Agents
  • Biomarkers
  • Endothelin A Receptor Antagonists
  • Peptide Fragments
  • Phenylpropionates
  • Pyridazines
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain
  • ambrisentan

Associated data

  • ClinicalTrials.gov/NCT01808313