Evidence map›Paper›PMID 42071815›Full record

SynthesisMedicine2026

Optimizing riociguat therapy for pulmonary hypertension: A systematic review and meta-analysis of dose variability, safety, and efficacy.

Muhammad Aqib Faizan, Tooba Rehman, Hurais Malik, Muhammad Hudaib, Muhammad Abdullah Tahir, Gunvi Ohri, Saher Bano, Laveeza Fatima, Syed Hassan Ahmed, Ayat Ul Karam and 6 more

Abstract readSystematic ReviewMeta-Analysis
In one paragraph

Synthesis in 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
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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

16 authors.

Muhammad Aqib FaizanDepartment of Medicine, Gomal Medical College, Khyber Medical University, Pakistan.
Tooba RehmanDepartment of Medicine, Gomal Medical College, Khyber Medical University, Pakistan.
Hurais MalikDepartment of Medicine, Fazaia Ruth Pfau Medical College, Karachi, Pakistan.
Muhammad HudaibDepartment of Medicine, Fazaia Ruth Pfau Medical College, Karachi, Pakistan.
Muhammad Abdullah TahirDepartment of Medicine, Fazaia Ruth Pfau Medical College, Karachi, Pakistan.
Gunvi OhriDepartment of Medicine, Dr. Sampurnanand Medical College, Jodhpur, India.
Saher BanoDepartment of Medicine, Ayub Medical College, Abbottabad, Pakistan.
Laveeza FatimaDepartment of Medicine, Allama Iqbal Medical College, Lahore, Pakistan.
Syed Hassan AhmedDepartment of Medicine, Ruth KM Pfau Civil Hospital, Karachi, Pakistan.
Ayat Ul KaramDepartment of Medicine, Fazaia Ruth Pfau Medical College, Karachi, Pakistan.
Zuhair AhmedDepartment of Medicine, Fazaia Ruth Pfau Medical College, Karachi, Pakistan.
Abdul RehmanDepartment of Medicine, Fazaia Ruth Pfau Medical College, Karachi, Pakistan.
Samra RabbaniDepartment of Medicine, Dow University of Health Sciences, Karachi, Pakistan.
Mrunalini DandamudiDepartment of Medicine, Montefiore Einstein Hospital, New York, NY.
Mohammed Mahmmoud Fadelallah EljackDepartment of Community Medicine, University of Bakht Alruda, Ed Dueim, Sudan.ORCID 0000-0002-2370-9368
Zainab HumayunDepartment of Medicine, University of Missouri, Kansas City, MO.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPulmonary hypertension (PH) is a progressive, life-threatening condition characterized by elevated pulmonary arterial pressure, often culminating in right heart failure. Despite existing therapies, optimizing treatment efficacy and safety remains a clinical challenge. Riociguat, a soluble guanylate cyclase stimulator, has shown promise in managing PH, particularly in pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). This meta-analysis aims to evaluate the optimal dosing of riociguat to maximize therapeutic benefits while minimizing adverse effects.

methodsThis systematic review and meta-analysis followed PRISMA guidelines. A comprehensive search of PubMed, Cochrane Central, Embase, and Google Scholar was conducted to identify randomized controlled trials (RCTs) comparing riociguat with placebo in adult PH patients. Eligible studies included double-arm RCTs with riociguat dosages ranging from 0.5 to 2.5 mg. Primary outcomes included changes in 6-minute walk distance (6-MWD), mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR), and NT-proBNP levels. Secondary outcomes were adverse events and clinical worsening. Study quality was assessed using the Cochrane risk of bias tool. Statistical analysis used RevMan 5.4 with a random-effects model. Heterogeneity was evaluated using χ2 and I2 tests, and meta-regression assessed the impact of age and BMI.

resultsTen RCTs involving 1109 PH patients were included. Riociguat significantly improved 6-MWD (MD: 27.23 m; 95% CI: 8.28-46.18; P = .005), reduced mPAP (MD: -2.61 mm Hg; 95% CI: -4.60 to -0.63; P = .01), lowered PVR (MD: -90.27 dynes·s·cm-5; 95% CI: -119.30 to -61.23; P < .00001), and decreased NT-proBNP levels (MD: -256.77 pg/mL; 95% CI: -491.99 to -21.55; P = .03). Meta-regression showed age and BMI significantly influenced treatment effects.

conclusionsRiociguat demonstrates dose-dependent efficacy in improving functional and hemodynamic parameters in PH, with the 2.5 mg thrice-daily dose showing consistent benefit. BMI impacted functional outcomes but not hemodynamic measures. These findings support tailored dosing strategies for optimized patient outcomes. Further research is needed to confirm dose-response effects and address residual heterogeneity.

Indexed as

Hypertension, PulmonaryPyrazolesPyrimidinesDose-Response Relationship, DrugHumansNatriuretic Peptide, BrainRandomized Controlled Trials as TopicTreatment OutcomeVascular ResistanceNatriuretic Peptide, BrainPyrazolesPyrimidinesriociguatdose variabilityefficacymeta-analysispulmonary hypertensionrandomized controlled trialsriociguatsafetysystematic review

Identifiers

PMID42071815
PMCPMC13124407

What Socratic holds

Textmetadata
LicenceCC BY
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Registered trials

None linked

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.