Evidence mapPaperPMID 42238623Full record

SynthesisReviews in cardiovascular medicine2026

Indirect Treatment Comparison of Riociguat Replacement Therapy and Selexipag Add-on Therapy in Patients With Pulmonary Arterial Hypertension: Results From a Systematic Review.

Ji-Eun An, Jahyun Cho, Min Ju Kim, Ah-Yeon Lee, Woo-Jeong Sim, Gyeong-U Hong, Soo Hyun Lee, Dong-Sook Kim, Sun-Young Yi, Kyung-Min Lee and 1 more

Abstract readSystematic Review
In one paragraph

Synthesis in Reviews in cardiovascular medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Ji-Eun AnCollege of Pharmacy, Kangwon National University, 24341 Kangwon, Republic of Korea.ORCID https://orcid.org/0009-0009-3734-6594
Jahyun ChoGraduate School of Public Health, Seoul National University, 08826 Seoul, Republic of Korea.ORCID https://orcid.org/0000-0001-6008-3774
Min Ju KimDepartment of Medical Information, School of Nursing and Health, Kongju National University, 32588 Kongju, Republic of Korea.ORCID https://orcid.org/0009-0009-5126-4317
Ah-Yeon LeeDepartment of Medical Information, School of Nursing and Health, Kongju National University, 32588 Kongju, Republic of Korea.ORCID https://orcid.org/0009-0003-6220-5247
Woo-Jeong SimDepartment of Medical Information, School of Nursing and Health, Kongju National University, 32588 Kongju, Republic of Korea.ORCID https://orcid.org/0009-0001-0975-2669
Gyeong-U HongDepartment of Medical Information, School of Nursing and Health, Kongju National University, 32588 Kongju, Republic of Korea.ORCID https://orcid.org/0009-0008-7003-1458
Soo Hyun LeeDepartment of Medical Information, School of Nursing and Health, Kongju National University, 32588 Kongju, Republic of Korea.ORCID https://orcid.org/0000-0003-1863-8371
Dong-Sook KimDepartment of Health Administration, School of Nursing and Health, Kongju National University, 32588 Kongju, Republic of Korea.ORCID https://orcid.org/0000-0003-2372-1807
Sun-Young YiDepartment of Market Access, Bayer Korea, 07335 Seoul, Republic of Korea.
Kyung-Min LeeDepartment of Market Access, Bayer Korea, 07335 Seoul, Republic of Korea.ORCID https://orcid.org/0009-0000-3525-5917
Su-Yeon YuCollege of Pharmacy, Kangwon National University, 24341 Kangwon, Republic of Korea.ORCID https://orcid.org/0000-0001-5488-5068

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Despite standard combination therapy with endothelin receptor antagonists (ERAs) and phosphodiesterase-5 inhibitors (PDE5is), many patients with pulmonary arterial hypertension (PAH) show inadequate therapeutic responses. Riociguat (a soluble guanylate cyclase stimulator) and selexipag (a prostacyclin receptor agonist) are both approved as next-step therapies; however, their comparative effectiveness and safety remain unknown due to the lack of head-to-head trials. We aimed to compare the therapeutic effects of riociguat replacement and selexipag add-on therapy through an indirect treatment comparison. Methods: Randomized controlled trials (RCTs) involving patients with PAH receiving either riociguat or selexipag were identified through a systematic search of PubMed, EMBASE, and the Cochrane Library up to 04 November 2025. This systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. Study quality was assessed with Cochrane's Risk of Bias 2.0 tool. Indirect treatment comparisons using Bucher's method were conducted within a common comparator (ERA + PDE5i) framework. Results: Three RCTs (four publications) were included: REPLACE, GRIPHON (main and post-hoc analyses), and a phase II trial. The overall risk of bias was low, except for the phase II trial, which had unclear risk due to its small sample size. Indirect comparisons showed no significant differences between the therapies for any outcome. The hazard ratio for clinical worsening was 0.167 (95% confidence interval [CI]: 0.0019-1.495, Conclusions: We found no significant differences between riociguat replacement and selexipag add-on therapy. These findings provide comparative data to help clinicians and patients make informed treatment decisions. Further head-to-head trials are needed to confirm comparative effectiveness. This review adhered to PRISMA 2020 guidelines. The PROSPERO Registration: CRD42024524391 https://www.crd.york.ac.uk/PROSPERO/view/CRD42024524391.

Indexed as

comparative effectiveness researchpulmonary hypertensionriociguatselexipagsystematic review

Identifiers

PMID42238623
PMCPMC13227382

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.