Pulmonary hypertension · Soluble guanylate cyclase stimulators
Riociguat for the treatment of pulmonary arterial hypertension
| Design | Phase 3, randomised, double-blind, placebo-controlled trial |
|---|---|
| Treatment | Riociguat titrated to a maximum of 2.5 mg three times daily |
| Control | Placebo |
| Population | 443 patients with pulmonary arterial hypertension, including those on endothelin receptor antagonists or prostanoids |
| Follow-up | 12 weeks |
| Primary endpoint | Change in six-minute walk distance at week 12 |
| Result | Six-minute walk distance increased by a mean of 30 m in the riociguat group and fell by 6 m with placebo — least-squares mean difference 36 m (95% CI 20 to 52, p<0.001). Benefit was seen both in untreated patients and in those on endothelin receptor antagonists or prostanoids. Pulmonary vascular resistance, NT-proBNP and WHO functional class all improved significantly. |
| Secondary endpoints | Pulmonary vascular resistance, NT-proBNP, WHO functional class, time to clinical worsening |
Riociguat significantly improved exercise capacity and secondary efficacy end points in patients with pulmonary arterial hypertension.
The trial authors, in the published abstract
A distinct mechanism from the phosphodiesterase-5 inhibitors, stimulating soluble guanylate cyclase directly rather than preventing cGMP breakdown — which is why it works when added to other agents, and why it must never be combined with a PDE5 inhibitor. Its companion trial in chronic thromboembolic disease gave that group its first licensed drug.
Ghofrani HA, Galiè N, Grimminger F, et al. Riociguat for the treatment of pulmonary arterial hypertension. N Engl J Med 2013 Jul 25;369(4):330-40.