Ambrisentan may improve certain hemodynamic parameters in patients with systemic sclerosis (SSc)-associated mildly elevated mean pulmonary arterial pressure (mPAP), according to research results published in Arthritis Research & Therapy. While the ambrisentan treatment group did not experience significant changes in mean mPAP, improvements were observed in cardiac index, pulmonary vascular resistance, and total pulmonary resistance.
The Early Treatment of Borderline Pulmonary Arterial Hypertension Associated With Systemic Sclerosis (EDITA) study (ClinicalTrials.gov Identifier: NCT02290613), a randomized, placebo-controlled, double-blind, parallel group trial, evaluated the effect of ambrisentan on mPAP in patients with SSc. Patients with diffuse cutaneous SSc and limited cutaneous SSc were eligible in the study if they had mildly elevated resting (21-24 mmHg) and/or exercise-induced (>30 mmHg) mPAP levels. Patients were randomly assigned 1:1 to receive ambrisentan or placebo. Ambrisentan treatment began at a dose of 5 mg/d and was titrated to a maximum dose of 10 mg/d following 1 to 4 weeks of treatment. Study assessments were conducted at baseline and after 3 and 6 months of treatment.
The primary end point was change from baseline to 6 months in resting mPAP. Secondary end points included changes in cardiac index, pulmonary vascular resistance, total pulmonary resistance, and other hemodynamic parameters. Safety events were assessed throughout the trial.
A total of 32 patients completed the study: 15 in the placebo group and 17 in the ambrisentan group. The majority of patients (78.9%) were women and the mean age was 56.8±11.0 years. A total of 60.5% of patients had limited cutaneous SSc and the remaining 39.5% had diffuse cutaneous SSc. Mean change in resting mPAP from baseline to 6 months was not significantly different between trial groups (ambrisentan, -1.00±6.40; placebo, -0.73±3.59; P =.884). At 6 months, 5 patients (2 from the treatment group) presented with mPAP values exceeding 25 mmHg. The 3 patients in the placebo group were classified with manifest SSc-associated pulmonary arterial hypertension and the 2 patients in the ambrisentan group with manifest pulmonary hypertension. Compared with the placebo group, patients in the ambrisentan group showed significant increases in cardiac index at rest (-0.31±0.71 L/min/m2 vs 0.36±0.66 L/min/m2; P =.010) and during exercise (-0.45±1.36 L/min/m2 vs 0.7±0.81 L/min/m3; P =.015). The ambrisentan vs placebo group also displayed significantly decreased pulmonary vascular resistance at rest (-0.70±0.78 Wood Units [WU] vs 0.01±0.71 WU; P =.012) and during exercise (-0.84±0.48 WU vs -0.0032±0.34 WU; P <.0001) at 6 months. Change in total pulmonary resistance differed significantly between groups; mean values decreased in the ambrisentan group and increased in the placebo group (P =.022).
Treatment-emergent adverse events were typically of mild or moderate severity. All serious adverse events occurred in the placebo group and resolved by the end of the trial period.
Although the primary trial end point was not met, ambrisentan was associated with significant improvements in other modalities of pulmonary function. The short trial duration limited the observation of more “distinct changes in pulmonary hemodynamics,” the researchers wrote. Further study in a larger cohort is necessary to enumerate the effects of ambrisentan.
Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Pan Z, Marra AM, Benjamin N, et al. Early treatment with ambrisentan of mildly elevated mean pulmonary arterial pressure associated with systemic sclerosis: a randomized, controlled, double-blind, parallel group study (EDITA study). Arthritis Res Ther. 2019;21(1):217.