Search

Introduction: Selexipag, an oral selective prostacyclin receptor agonist, delays disease progression versus placebo in pulmonary arterial hypertension (PAH). In appropriate patients, transitioning from parenteral prostacyclin analogs to selexipag may alleviate the risks associated with long-term parenteral therapy. We report our experience with the feasibility, safety and challenges associated with systematic transition from parenteral prostacyclin therapy to selexipag in compensated PAH. Methods: From Jan. 2016 to July 2017, patients with PAH at Duke University Medical Center who were stable on parenteral prostacyclin therapy were offered the opportunity to transition to selexipag via standardized protocol. Patients underwent pre- and post-transition assessments of hemodynamics, echocardiography, biomarkers, and functional status. Patient demographics, clinical characteristics and any adverse effects were recorded in a database. Data are presented as median (Q1, Q3) unless specified. Results: Overall, 14 patients (11 women; age 53 years (48, 59); BMI 30.1 kg/m2 (26.9, 33.2)) were included with median follow-up of 5.5 months (4.1, 6.4). Of these, 13 patients tolerated the transition to selexipag and remained on drug (total daily dose 3200 mcg (3200, 4800)) at study completion. Two patients required an additional PAH medication during and after the transition period. Overall, pre- and post-transition NT-proBNP, 6MWD, TAPSE, RV function, and hemodynamics were stable (Table 1). The patient who failed the switch as assessed by worsening symptoms and surrogate markers had portopulmonary hypertension with intravenous therapy complicated by catheter-associated infection prior to the switch. Conclusions: The transition from parenteral prostacyclin therapy to selexipag was generally well tolerated in patients with compensated PAH. Our results support further study of the long-term implications of this transition in appropriate patients. [ABSTRACT FROM AUTHOR]

Introduction: Echocardiography is a key tool in the management of patients with pulmonary arterial hypertension (PAH), but many potential parameters could be used to assess response to therapy. We examined echocardiographic variables before and after initiation of PAH-specific therapy to evaluate which measures of RV function were best correlated with clinical outcomes. Methods: This retrospective study included all patients with PAH seen at Duke University Medical Center from 2010 to 2013 who had TTEs with RV-focused views and RV strain assessment performed within 6 months pre- and post-initiation of a PAH-specific therapy and had no significant intercurrent illness. In a series of exploratory analyses, pre- and post-therapy TTE parameters were compared using the Wilcoxon signed rank test, changes in TTE parameters were compared to changes in 6MWD using Spearman rank-order correlations, and Cox regression was used to assess the relationship of pre-treatment values and changes in these parameters with all-cause mortality over the 3-year period following post-treatment TTE. All data reported as median (Q1, Q3) unless specified. Results: Our cohort included 48 patients (35 women, age 49 yrs (35, 56)) with severe PAH at baseline (mPAP 50 mmHg (41, 60); PVR 8.8 Wood units (5.6, 13.9)). TAPSE, 6MWD, mid-RV and basal-RV diameters, RVSP, and RV global longitudinal strain (GLS) were all found to significantly improve after initiation of PAH therapy. Decreases in RA area (r = -0.50, p = 0.002) and mid-RV diameter (r = -0.36, p = 0.033) were most strongly correlated with improvement in 6MWD. Overall, 14 patients (32%) died within 3-years. Pre-treatment values of RA area (HR per 1 unit: 1.15; 95% CI 1.06, 1.24), mid-RV diameter (HR: 2.85; 1.30, 6.23), basal-RV diameter (HR: 3.5; 1.66, 7.35) and RV GLS (HR: 1.20; 1.04, 1.37) were all associated with increased mortality risk. TAPSE was unique in that pre-treatment TAPSE (HR: 0.17; 0.04, 0.67) and interval increase in TAPSE (HR: 0.18; 0.06, 0.62) were both significantly associated with decreased mortality risk. Conclusions: Given the strong association of both baseline TAPSE and change in TAPSE with mortality, our study supports the ongoing use of TAPSE as an important assessment of disease severity and treatment response in PAH. [ABSTRACT FROM AUTHOR]