Transitioning Prostacyclin Pathway Agents to Oral Selexipag in Patients with Pulmonary Arterial Hypertension: A Systematic Literature Review

Figures

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  Fig. 1. Key takeaways from the SLR. *As explicitly defined by study authors for each publication. PPA prostacyclin pathway agent, SLR systematic literature review

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  Fig. 2. PRISMA flow diagram. Excludes were based on the PICOS criteria (Supplementary Appendix 3), including publications not reporting on patients meeting the population inclusion criteria, reporting on patients not receiving the interventions of interest (i.e., transition to oral selexipag from other PPAs), not reporting on any of the outcomes of interest, or with an excluding study design. *Additional conference abstracts captured through gray literature searching not identified through the database searches (in total 20 conference abstracts were included in the SLR; 16 through the database searches and 4 through gray literature searches). Congresses in scope included ACC, CHEST, AHA, ATS, ERS, ESC, HFSA, ISHLT, PHA, PHPN, PVRI, and SCCM. Identified abstracts included two conference abstracts from PHA and two from PHPN. **Publications reporting on pediatric populations were not extracted as per the PICOS criteria. Consequently, results from these publications are not reported in this SLR. ACC American College of Cardiology, AHA American Heart Association, ATS American Thoracic Society, CHEST American College of Chest Physicians, ERS European Respiratory Society, ESC European Society…

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  Fig. 3. Interventions from which patients were transitioned to oral selexipag by study type. Note: The total number of publications reporting on each administration may exceed the total number of included publications, as publications may have reported results for more than one route of administration (highlighted with*). **For publications that did not specify the route of administration for epoprostenol (case reports: N = 1; case series: N = 3; observational/interventional studies: N = 3), it has been inferred that the route is intravenous as intravenous administration is the only approved route. EPO epoprostenol, INH inhaled, IV intravenous, NR not reported, PO oral, PAR parenteral, PPA prostacyclin pathway agent, SC subcutaneous, TREP treprostinil

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  Fig. 4. Transition protocols reported in identified publications, categorized by transition approach and speed*. NR not reported. Please note that some publications reported multiple transition approaches, either in different transition protocols used for different patients in the same study or within the same transition protocols. The figure showing transition speed only considers publications that explicitly mentioned a specific speed of transition. *Transition approach and transition speed were categorized based on information explicitly reported in the included publications. Transition approach refers to the protocol method used to implement the transition from PPAs to oral selexipag, as described in the included publications. Transition speed refers to the pace at which patients were transitioned from PPAs to oral selexipag, as noted where explicitly reported by each publication. **One of the identified publications described titration as “slow”; however, no specific timeframe was provided for the transition. Prolonged titration was reported as 674 days. ***“Rapid” transition ranged from 2 to 5 days across the three publications

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  Fig. 5. Number of publications reporting on different measured outcomes*. *Publications may have reported more than one measurement for different patients. **Risk score was assessed via the REVEAL 2.0 or the Swedish PAH Registry (SPAHR) and the German COMPERA model. †Publications reporting on patients remaining on selexipag at completion of the study period, versus patients discontinuing oral selexipag following transition. 6MWD 6-min walking distance, NT-ProBNP N-terminal pro-B-type natriuretic peptide, RHC right heart catheterization, RV right ventricular

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  Fig. 6. Number of a hemodynamic parameters and b echocardiographic parameters reported across publications*. *Publications may have reported more than one measurement for different patients. **RV diastolic pressure was also referred to as end-diastolic pressure in publications; these outcomes have been combined due to the interchangeable use of terms. RV diastolic pressure and RV end-diastolic pressure are often used interchangeably, as RV diastolic pressure is typically measured at the end of diastole and reflects RV filling pressure and preload [64]. CI cardiac index, PA pulmonary artery, PAP pulmonary artery pressure, PVR pulmonary vascular resistance, RAP right atrial pressure, RV right ventricular, TAPSE tricuspid annular plane systolic excursion, TRPG tricuspid regurgitation pressure gradient