Does treatment of inoperable chronic thromboembolic pulmonary hypertension require multimodality approach?
France: Balloon pulmonary angioplasty (BPA) and riociguat are treatment options for inoperable chronic thromboembolic pulmonary hypertension (CTEPH). A recent study comparing the two treatments found pulmonary vascular resistance reduction to be more pronounced with BPA compared to riociguat at week 26. Treatment-related serious adverse events were, however, more common with BPA.
The discovery in the follow-up study that BPA-related serious adverse events were fewer among patients who were pretreated with riociguat versus those who received BPA as first-line treatment indicates the potential benefits of a multimodality approach to treatment in patients with inoperable CTEPH. The study was published in The Lancet Respiratory Medicine.
The study was conducted by Xavier Jaïs, Université Paris-Saclay, Faculté de Médecine, Le Kremlin-Bicêtre, France, and colleagues with the objective to evaluate the safety and efficacy of BPA versus riociguat in patients with inoperable CTEPH in phase 3, multicentre, open-label, parallel-group, randomized controlled trial.
For this purpose, the researchers enrolled treatment-naive patients aged 18–80 years with newly diagnosed, inoperable CTEPH and pulmonary vascular resistance of more than 320 dyn·s/cm5 from 23 French centers of expertise for pulmonary hypertension. Patients were randomly assigned in the ratio of 1:1 to receive BPA or riociguat.
The change in pulmonary vascular resistance at week 26, expressed as a percentage of baseline pulmonary vascular resistance in the intention-to-treat population was the study's primary endpoint.
Safety analyses were done in all patients who received at least one dose of riociguat or had at least one BPA session. The patients who completed the RACE trial were included in an ancillary 26-week follow-up. During the follow-up, symptomatic patients with pulmonary vascular resistance of more than 320 dyn·s/cm5 benefited from add-on riociguat after BPA or add-on BPA after riociguat.
105 patients were randomly assigned to riociguat (n=53) or BPA (n=52) between Jan 19, 2016, and Jan 18, 2019.
The key findings of the study were as follows:
· At week 26, the geometric mean pulmonary vascular resistance decreased to 39·9% of baseline pulmonary vascular resistance in the BPA group and 66·7% of baseline pulmonary vascular resistance in the riociguat group (ratio of geometric means 0·60).
· Treatment-related serious adverse events occurred in 22 (42%) of 52 patients in the BPA group and five (9%) of 53 patients in the riociguat group.
· The most frequent treatment-related serious adverse events were lung injury (18 [35%] of 52 patients) in the BPA group and severe hypotension with syncope (two [4%] of 53 patients) in the riociguat group.
· There were no treatment-related deaths.
· At week 52, a similar reduction in pulmonary vascular resistance was observed in patients treated with first-line riociguat or first-line BPA.
· The incidence of BPA-related serious adverse events was lower in patients who were pretreated with riociguat (five [14%] of 36 patients vs 22 [42%] of 52 patients).
"Further studies are needed to explore the effects of sequential treatment combining one or two medications and BPA in patients with inoperable CTEPH," the authors concluded.
Reference:
The study titled, "Balloon pulmonary angioplasty versus riociguat for the treatment of inoperable chronic thromboembolic pulmonary hypertension (RACE): a multicentre, phase 3, open-label, randomised controlled trial and ancillary follow-up study," was published in The Lancet Respiratory Medicine.
DOI: https://doi.org/10.1016/S2213-2600(22)00214-4
