Upfront combination therapy with riociguat and treprostinil yielded similar 12-week improvements in BNP (p=0.719) and mPAP (p=0.673) vs treprostinil monotherapy, but 31% discontinued riociguat.
Observational (n=32)
Does upfront combination therapy with riociguat and treprostinil improve BNP, mPAP, and TAPSE compared with treprostinil monotherapy in patients with severe Group 1 PAH?
Upfront combination therapy with riociguat and treprostinil in severe PAH showed similar short-term hemodynamic improvements to treprostinil monotherapy but with higher rates of adverse events.
p-value: p=BNP p=0.719, mPAP p=0.673, TAPSE p=0.997
Abstract Rationale While upfront combination therapy is standard in severe pulmonary arterial hypertension (PAH), evidence supporting this strategy in functional class IV patients is limited. We tested whether concurrent initiation of riociguat (Adempas) and treprostinil produces synergistic hemodynamic and clinical benefits compared with delayed combination therapy following treprostinil monotherapy. Methods Sixteen patients with severe Group 1 PAH were treated with upfront riociguat (Adempas) and treprostinil (intervention group). Outcomes were retrospectively compared with age- and sex-matched patients (n = 16) who received upfront treprostinil monotherapy (control group). Baseline group differences were evaluated using the Mann-Whitney U test, and between-group effects over time were assessed with repeated-measures analysis of variance. Data is presented as mean ± standard deviation. Results At baseline, the control group had a mean brain natriuretic peptide (BNP) level of 1310 ± 2213 nanogram per liter (ng/L), mean pulmonary arterial pressure (mPAP) of 58.0 ± 9.6 millimeters of mercury (mmHg), and tricuspid annular plane systolic excursion (TAPSE) of 1.44 ± 0.57 centimeters (cm). The intervention group had corresponding values of 1862 ± 1529 ng/L, 53.3 ± 8.7 mmHg, and 1.47 ± 0.46 cm, respectively. There were no significant baseline differences in BNP, mPAP, or TAPSE between groups. Over 12 weeks, both groups showed significant improvement in BNP (p = 0.019) and mPAP (p 0.001), whereas TAPSE did not significantly change (p = 0.137). When comparing the magnitude of improvement between the two groups, no statistically significant differences were observed for BNP (p = 0.719), mPAP (p = 0.673), or TAPSE (p = 0.997). Five patients (31%) in the intervention group discontinued riociguat due to adverse events; no participants discontinued treprostinil in either group. Conclusions Although upfront combination therapy with riociguat and treprostinil yielded similar short-term improvements in BNP and mPAP compared with treprostinil monotherapy, it was associated with a higher rate of adverse events. These findings suggest that the potential benefits of early combination therapy in severe PAH should be balanced against increased tolerability concerns. Larger studies are needed to clarify whether the timing of combination therapy influences both efficacy and safety in functional class IV disease. This abstract is funded by: Bayer Pharmaceuticals
Tishkoff et al. (Fri,) conducted a observational in Severe Group 1 pulmonary arterial hypertension (n=32). Upfront combination therapy with riociguat and treprostinil vs. Upfront treprostinil monotherapy was evaluated on Magnitude of improvement in BNP, mPAP, and TAPSE (p=BNP p=0.719, mPAP p=0.673, TAPSE p=0.997). Upfront combination therapy with riociguat and treprostinil yielded similar 12-week improvements in BNP (p=0.719) and mPAP (p=0.673) vs treprostinil monotherapy, but 31% discontinued riociguat.