Abstract 14354: The Impact of Riociguat in Pulmonary Arterial Hypertension Patients With Comorbidities Included in Interventional Clinical Trials

Background: The number of pulmonary arterial hypertension (PAH) patients with comorbidities is increasing, however, there are few published data from these patients in PAH therapy clinical trials meaning that evidence-based treatment recommendations have not been made.

Aim: This post-hoc analysis of pooled riociguat clinical trial data assessed the impact of riociguat in patients with PAH and comorbidities.

Methods: All interventional studies of riociguat in patients with PAH (PATENT-1, PATENT PLUS, RESPITE, MOTION, REPLACE, and the Phase II study) were included in the pooled analysis. The safety of riociguat and placebo was assessed in patients with ≥3 comorbidities vs <3 comorbidities. Safety was assessed by adverse events (AEs) and serious AEs (SAEs). Comorbidities included: age ≥65 years, body mass index ≥30 kg/m ² , history of essential hypertension, diabetes mellitus, history of significant coronary artery disease, and atrial fibrillation.

Results: The 609 patients who received riociguat and 132 patients who received placebo in the main phase clinical trials of riociguat were included in the analysis. Of these, 113 patients (19%) in the riociguat group and 21 patients (16%) in the placebo group had ≥3 comorbidities. In both treatment groups, AE rates were higher in patients with ≥3 comorbidities vs <3 comorbidities (riociguat 93% vs 86%; placebo 95% vs 84%); with most AEs being mild or moderate. Study drug-related AE rates were similar in both treatment groups and in patients with ≥3 comorbidities vs <3 comorbidities (riociguat 54% vs 56%; placebo 52% vs 52%). SAE rates were higher in riociguat-treated patients with ≥3 comorbidities vs <3 comorbidities (25% vs 12%); of these, 4% and 3% were study drug-related, respectively. In patients with ≥3 comorbidities, study drug-related SAE rates were higher in those receiving placebo vs riociguat (10% vs 4%). AE rates leading to study drug discontinuation were higher in patients with ≥3 comorbidities vs <3 comorbidities (riociguat 6% vs 4%; placebo 10% vs 6%), whereas AE rates leading to death were similar in both groups (riociguat 2% vs 1%; placebo 0% vs 4%).

Conclusion: These data suggest that riociguat had an acceptable tolerability profile in PAH patients with comorbidities with most AEs being mild or moderate.