Review Study Supports Tracleer as Effective Treatment in Pulmonary Arterial Hypertension

Treatment with Tracleer (bosentan) is effective in patients with pulmonary arterial hypertension (PAH), a new review study and analysis of data from clinical trials shows.

The research, “Bosentan Therapy for Pulmonary Arterial Hypertension and Chronic Thromboembolic Pulmonary Hypertension: A Systemic Review and Meta-Analysis,” was published in The Clinical Respiratory Journal.

Exaggerated production of endothelin-1, a potent vasoconstrictor (narrowing of blood vessels), plays an important role in the development of PAH. As it blocks endothelin receptors, Tracleer (marketed by Actelion ) is able to provide a vasodilator (widening of blood vessels) effect.

A prior meta-analysis — a type of statistical study that combines the results of various studies — showed that Tracleer is able to improve exercise capacity and hemodynamics (the dynamics of blood flow) in PAH patients.

However, two of the studies used in the analysis were not conducted in PAH patients, but rather in patients with chronic thromboembolic pulmonary hypertension (CTEPH) and chronic obstructive pulmonary disease-related pulmonary hypertension (COPD-PH), which may have introduced bias.

Although research showed that treatment with Tracleer can also improve cardiopulmonary hemodynamics in CTEPH patients, the potential improvement in CTEPH symptoms with this medication remained unknown.

That led the research team to conduct a systematic review of the literature and a meta-analysis to determine the efficacy and safety of oral treatment with Tracleer for both PAH and CTEPH patients.

The study analyzed 10 clinical trials (eight in PAH and two in CTEPH) with random assignment of participants to Tracleer or placebo treatment groups. Overall, the trials included 1,185 patients (1,003 with PAH and 182 with CTEPH).

Results showed that, in PAH patients, Tracleer improved the six-minute walk distance (an exercise test measuring the distance an individual can walk over six minutes), reduced mean pulmonary arterial pressure by 5.7 mmHg (millimeters of mercury — the units used to measure blood pressure), and increased cardiac index (which assesses cardiac output per body surface area).

Tracleer also reduced vascular resistance in the lungs (which improves blood flow), and limited clinical and functional worsening.

In CTEPH patients, Tracleer also improved cardiac index and decreased pulmonary vascular resistance, though at a lower level than in PAH patients. This reduced efficacy in CTEPH patients may be due to the different nature of the diseases, the scientists hypothesized, including the lack of increased production of entothelin-1 in CTEPH.

The lack of improvement in exercise capacity and hemodynamics in CTEPH patients contrasts with previous analyses, the authors observed. This may be explained by methodological differences, as those prior studies compared the effects of Tracleer with the patients’ values at baseline, rather than with placebo treatment.

In both PAH and CTEPH patients, no differences were observed between Tracleer and placebo regarding mortality and adverse events. However, Tracleer increased the risk of abnormal liver function in both patient groups.

Overall, “[Tracleer] is effective in treating PAH, whereas it only improves certain hemodynamic parameters of CTEPH,” the researchers wrote.

Among the study’s limitations, longer follow-up periods are required to evaluate if the improvements seen with Tracleer are sustained over a longer term, the team observed. In addition, the small sample size and low number of clinical trials analyzed draw caution in the interpretation of the CTEPH results.