TOPLINE

Riociguat significantly reduced pulmonary vascular resistance (PVR) over 24 weeks in patients with early pulmonary vascular disease (PVD) and was safe and well tolerated, a phase 2a trial showed.

METHODOLOGY

• Researchers conducted a prospective, phase 2a trial across eight centers in Europe to evaluate the effect of riociguat in patients with early PVD.
• Early PVD was defined as mean pulmonary arterial pressure (mPAP) ≥ 25 mm Hg with PVR ≥ 2 to < 3 Wood units (WU), or mPAP 21 to < 25 mm Hg with PVR ≥ 2 WU, in connective tissue disease (CTD) or idiopathic/heritable forms.
• They enrolled 35 patients (mean age, 65.54 years; 97.10% women), of which 32 completed the study. Patients were randomly assigned to receive riociguat or placebo for 24 weeks, including an 8-week dose-adjustment phase followed by a 16-week maintenance phase.
• The primary endpoint was change in PVR from baseline to week 24. Secondary outcomes included changes in cardiac index, total pulmonary resistance, diffusing capacity of the lung for carbon monoxide, 6-minute walking distance, World Health Organization (WHO) functional class, and quality of life. Safety was assessed in all patients who received at least one dose of riociguat.

TAKEAWAY

• At 24 weeks, riociguat treatment significantly reduced PVR compared with placebo (mean decrease, 0.73 ± 0.67 WU vs 0.02 ± 0.67 WU; P = .043), yielding a 27% placebo-adjusted reduction.
• No significant differences were seen between groups in secondary endpoints, including cardiac index, 6-minute walking distance, WHO functional class, and quality of life.
• Cardiac output showed a trend toward improvement with riociguat vs placebo, although the difference was not statistically significant.
• The frequency of adverse events was similar between groups, with most being mild-to-moderate. Infections were the most frequent adverse events in both groups and were unrelated to riociguat. No deaths were reported.

IN PRACTICE

“The significant improvement in PVR indicates that riociguat may confer hemodynamic benefit in patients with early pulmonary vascular changes, potentially delaying disease progression,” the authors wrote.

SOURCE

The study was led by Panagiota Xanthouli, MD, Centre for Pulmonary Hypertension, Thoraxklinik Heidelberg gGmbH, Heidelberg University Hospital and Translational Lung Research Centre Heidelberg, Member of the German Centre for Lung Research, Heidelberg, Germany. It was published online on July 14, 2026, in Chest.

LIMITATIONS

Early study termination limited enrollment to 35 patients instead of the planned 70, reducing statistical power for secondary endpoints. Baseline imbalances in WHO functional class and 6-minute walking distance existed between groups. In addition, most participants were women with CTD-associated PVD, limiting generalizability to men and non-CTD populations.

DISCLOSURES

The study was supported in part by a research grant from the Investigators Studies Research Program of Merck Sharp & Dohme Corp. Authors reported receiving consulting fees, speaker fees, research grants, and travel support from multiple pharmaceutical companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.