In patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH), pretreatment with riociguat may improve hemodynamics prior to the use of balloon pulmonary angioplasty (BPA). Notably, BPA is not a replacement for medical therapy with riociguat in these patients. These were among clinical trial findings published in The Lancet Respiratory Medicine.

Recognizing that randomized trials comparing the use of riociguat and BPA as treatment options for patients with inoperable CTEPH are lacking, researchers sought to evaluate the efficacy and safety of BPA vs riociguat in patients with this condition.

The researchers conducted a phase 3, multicenter, open-label, parallel-group, randomized controlled RACE trial (ClinicalTrials.gov identifier: NCT02634203) in 23 French centers with expertise in the treatment of PH. Between January 2016 and through January 2019, the trial enrolled 105 treatment-naïve patients aged 18 to 80 years old, with newly diagnosed, inoperable CTEPH and pulmonary vascular resistance (PVR) of more than 320 dyn/s/cm5. All patients were randomly assigned in a 1:1 ratio to BPA (n=52) or riociguat (n=53) via a web-based randomization system.


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The primary study endpoint was change in PVR at week 26, which was expressed as the percentage of baseline PVR in the intention-to-treat population. Safety analyses were performed in all patients who received at least 1 dose of riociguat or underwent at least 1 BPA session. All patients who completed the RACE trial continued into an ancillary 26-week follow-up study, during which time symptomatic patients with PVR of more than 320 dyn/s/cm5 were shown to benefit from add-on riociguat after BPA or add-on BPA after riociguat therapy.

At 26 weeks, the geometric mean PVR decreased to 39.9% (95% CI, 36.2% to 44.0%) of baseline PVR in the BPA arm vs 66.7% (95% CI, 60.5% to 73.5%) of baseline PVR in the riociguat arm (ratio of geometric means, 0.60; 95% CI, 0.52-0.69; P <.0001).

Treatment-related serious adverse events (SAEs) were reported in 42% (22 of 52) of patients in the BPA group and 9% (5 of 53) of patients in the riociguat group. The most commonly reported SAEs included lung injury (35% of participants in the BPA arm) and severe hypotension with syncope (4% of patients in the riociguat arm). No treatment-related deaths were reported.

At week 52, a similar decrease in PVR was detected in patients treated with first-line riociguat or first-line BPA (ratio of geometric means, 0.91; 95% CI, 0.79-1.04). The incidence of BPA-associated SAEs was lower among patients who received pretreatment with riociguat (14% vs 42%, respectively).

Limitations of the current analysis include: lack of masking because of the comparison on an oral therapy with an interventional approach involving use of repeated invasive procedures over multiple weeks; smaller than expected sample size due to a funding deficit and study termination prior to reaching the randomization target; exclusion of patients with persistent or recurrent PH after undergoing pulmonary endarterectomy.

“BPA should not be regarded as a replacement for medical therapy in patients with inoperable CTEPH, but as a complementary treatment modality for use in conjunction with medical therapy, especially when patients present with severe haemodynamic compromise associated with a higher risk of BPA-induced lung injury,” study authors concluded. “Further studies are needed to explore the effects of sequential treatment combining one or two medications and BPA in patients with inoperable CTEPH,” they added.

Disclosure: Some of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 

Reference

Jaïs X, Brenot P, Bouvaist H, et al. 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. Lancet Respir Med. Published online August 1, 2022. doi:10.1016/S2213-2600(22)00214-4