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PULMONARY HYPERTENSION

Current evidence

Benefit and risk, in context.

Established PAH pathways lead. Treatment choice and sequence depend on phenotype and risk.

Benefit–risk waterfall

Qualitative balance · select a bar to explore

8 classes

Named categories, not a numerical benefit:risk ratio. Alphabetical within each category; bar height is not a head-to-head treatment ranking. Class ranges show reviewed member categories.

SELECTED CLASS

Activin signalling inhibitor

Favorable in established use

Class context summarizes only the stated PH group. Individual drugs, routes, doses and enrolled phenotypes remain distinct.

Sotatercept: Add-on sotatercept has established adult PAH functional and clinical-outcome evidence, with active hemoglobin, platelet and bleeding surveillance.

An established treatment in the stated indication, with active safety management. This does not mean risk-free or superior to another drug.

  • ZENITH studied selected high-risk patients and stopped early; its composite hazard reduction is not a mortality reduction.
  • Background therapy, eligibility and current product monitoring requirements constrain generalization.
  • Class placement is a conservative editorial summary, not a pooled effect, ratio or head-to-head comparison.
Sotatercept
Study reports & sources (26)
  • Adolescent sotatercept · Japanese case report · 2026Observational cohort · Tested therapy · Sotatercept · No confirmatory primary comparisonRouteSotatercept: Route awaiting full-text verification

    The primary abstract describes hemodynamic and RV improvement without adverse effects; it provides no controlled estimate.

    Route of administration

    • SotaterceptRoute awaiting full-text verification

      The indexed primary abstract does not state route. Publisher full text was inaccessible and the public repository endpoint failed; route was not inferred from the generic name.

    PH was not uniformly confirmed in this population.Explore trial report
  • HYPERION · RV echo secondary report · 2026Conference report · Tested therapy · Sotatercept · Secondary report · no separate primary comparisonRouteSotatercept: subcutaneous (SC) injection · parent protocol

    Median RVFAC change +6.49 vs +0.99 percentage points (140/144 paired); TAPSE did not notably differ.

    Route of administration

    • Sotaterceptsubcutaneous (SC) injection · parent protocol

      A044 identifies the HYPERION regimen; the linked parent NCT04811092 establishes SC administration every three weeks.

    Explore trial report
  • Pediatric sotatercept · PPHNet retrospective cohort · 2026Observational cohort · Tested therapy · Sotatercept · No confirmatory primary comparisonRouteSotatercept: subcutaneous (SC) injection

    Adverse events occurred in 33/66 and bleeding in 15/66, including a GI bleed requiring hospitalization/transfusion; one pulmonary AVM was reported. Paired walk distance increased a median 31 m (n=40); mPAP decreased 17 mmHg and indexed PVR 4.4 WU·m² (n=21). No deaths or worsening-PH hospitalizations were reported.

    Route of administration

    • Sotaterceptsubcutaneous (SC) injection

      The full report identifies the commercial Winrevair kit; SC injection is confirmed by the FDA product label cited in reference 12, although the cohort methods do not restate the route.

    PH was not uniformly confirmed in this population.Explore trial report
  • Pediatric sotatercept · Rady seven-patient cohort · 2026Observational cohort · Tested therapy · Sotatercept · No confirmatory primary comparisonRouteSotatercept: subcutaneous (SC) injection

    PVRI decreased in six of seven; mPAP responses varied. Two self-limited nosebleeds occurred; no hospitalization or dose interruption was reported.

    Route of administration

    • Sotaterceptsubcutaneous (SC) injection
    Explore trial report
  • PH RISE-ME · sotatercept routine-care cohort · 2026Observational cohort · Tested therapy · Sotatercept · No confirmatory primary comparisonRouteSotatercept: subcutaneous (SC) injection

    RA area changed −2.67 cm² (95% CI −4.16 to −1.18); walking did not significantly improve. Two all-cause deaths occurred. Follow-up included epistaxis in one and telangiectasia in two.

    Route of administration

    • Sotaterceptsubcutaneous (SC) injection

      Methods define exposure by documented SC administration; 0.3 mg/kg every three weeks, with individualized escalation to 0.7 mg/kg.

    Explore trial report
  • Sotatercept · Greek four-patient conference cohort · 2026Conference report · Tested therapy · Sotatercept · No confirmatory primary comparisonRouteSotatercept: Route awaiting full-method verification

    Walking changed 389 to 430 m; one discontinued for severe hemoptysis.

    Route of administration

    • SotaterceptRoute awaiting full-method verification

      The complete published conference abstract A156 does not state route; no separate methods report was located.

    PH was not uniformly confirmed in this population.Explore trial report
  • Sotatercept · Japanese phase III study 020 · 2026Single-arm study · Tested therapy · Sotatercept · No confirmatory primary comparisonRouteSotatercept: subcutaneous (SC) injection

    Estimated PVR change was −99.2 dyn·s·cm⁻⁵ (95% CI −129.6 to −68.4); walk distance increased 41.8 m. Six participants (13%) had serious adverse events during the primary period. A post-cutoff gastrointestinal-hemorrhage death, 88 days after the last dose and outside the 56-day safety window, was considered intervention-related by the investigator.

    Route of administration

    • Sotaterceptsubcutaneous (SC) injection
    Explore trial report
  • Sotatercept · Ohio State first-year practice · 2026Conference report · Tested therapy · Sotatercept · No confirmatory primary comparisonRouteSotatercept: subcutaneous (SC) injection · manufacturer regimen

    Fifteen dose reductions for polycythemia or thrombocytopenia; prostacyclin reduced/stopped in 11 and parenteral-to-oral transition in five.

    Route of administration

    • Sotaterceptsubcutaneous (SC) injection · manufacturer regimen

      A010 explicitly states use of manufacturer initiation/management instructions; the cited approved Winrevair formulation is SC injection. Abstract does not independently repeat route.

    PH was not uniformly confirmed in this population.Explore trial report
  • Sotatercept · serial CMR case report · 2026Observational cohort · Tested therapy · Sotatercept · No confirmatory primary comparisonRouteSotatercept: subcutaneous (SC) injection

    At six months after sotatercept, functional class was I despite persistent RV dilation. Later SC treprostinil withdrawal was reported. A minor hemoglobin increase occurred.

    Route of administration

    • Sotaterceptsubcutaneous (SC) injection

      Case presentation explicitly states SC sotatercept every three weeks, initially 0.3 then 0.7 mg/kg; SC treprostinil was co-therapy, not the same formulation.

    Explore trial report
  • Sotatercept · SSc capillaroscopy and bleeding case · 2026Observational cohort · Tested therapy · Sotatercept · No confirmatory primary comparison · Harm signalRouteSotatercept: Route awaiting accessible Methods

    Pulmonary hemodynamics improved while capillary dilation and microhemorrhages increased; new recurrent gingival bleeding and epistaxis were reported. Background vasoactive therapy was unchanged.

    Route of administration

    • SotaterceptRoute awaiting accessible Methods

      Complete primary letter, figure caption and case text were reviewed; neither route nor a study-specific dosing statement is provided. No route was inferred from the generic name.

    Explore trial report
  • Sotatercept · two Eisenmenger cases · 2026Conference report · Tested therapy · Sotatercept · No confirmatory primary comparisonRouteSotatercept: Route awaiting full-method verification

    One temporary gingival bleed; no significant Hb rise reported. Physiological/functional improvement was descriptive.

    Route of administration

    • SotaterceptRoute awaiting full-method verification

      The complete published abstract does not state administration route; no route was inferred from the generic agent name.

    PH was not uniformly confirmed in this population.Explore trial report
  • Sotatercept · two-center US experience · 2026Conference report · Tested therapy · Sotatercept · No confirmatory primary comparisonRouteSotatercept: Route awaiting full-method verification

    Three stopped: two for thrombocytopenia, one for severe epistaxis. Seven paired-RHC cases showed mean PVR reduction of 37%.

    Route of administration

    • SotaterceptRoute awaiting full-method verification

      The complete published abstract does not state administration route; no route was inferred from the generic agent name.

    PH was not uniformly confirmed in this population.Explore trial report
  • Sotatercept + macitentan · CTD/ILD overlap case · 2026Observational cohort · Combination regimen · Sotatercept · No confirmatory primary comparisonRoutesSotatercept: Full-text route verification pendingMacitentan: Full-text route verification pendingTreprostinil: Prior treatment · inhaledTadalafil: Prior treatment · full-text route verification pending

    Functional class I and improved hemodynamic/echo findings were reported; resting oxygen saturation rose from 93% to 96%, followed by bilateral lung transplantation.

    Route of administration

    • SotaterceptFull-text route verification pending

      Primary abstract identifies the drug; publisher full-paper/PDF access returned 403. Do not infer this patient’s route from the generic drug name.

    • MacitentanFull-text route verification pending

      Primary abstract identifies the concurrent drug but not its formulation/route; full-paper access is currently blocked.

    • TreprostinilPrior treatment · inhaled

      Inhalation is explicit in the primary abstract; nebulized versus dry-powder formulation is not established.

    • TadalafilPrior treatment · full-text route verification pending

      Prior tadalafil is identified in the primary abstract, but its case-specific route is awaiting full-text verification.

    PH was not uniformly confirmed in this population.Explore trial report
  • Sotatercept after Potts shunt · two salvage cases · 2026Observational cohort · Tested therapy · Sotatercept · No confirmatory primary comparisonRouteSotatercept: Route not stated in full report

    Stabilization was reported within 48 hours; vasoactive support was withdrawn within one week. Treprostinil was subsequently withdrawn during follow-up.

    Route of administration

    • SotaterceptRoute not stated in full report

      The complete case descriptions specify a single 0.3 mg/kg dose but do not restate its administration route or identify a study-specific product instruction. The explicitly described IV/SC routes concern background treprostinil.

    Explore trial report
  • Upfront sotatercept combination · SSc-PAH case · 2026Observational cohort · Combination regimen · Sotatercept · No confirmatory primary comparisonRoutesSotatercept: Route not stated in full reportMacitentan: OralTadalafil: Oral

    PVR fell to 3.7 WU and CI rose to 2.90 L/min/m²; functional class III to II. No sotatercept-attributed adverse event was reported.

    Route of administration

    • SotaterceptRoute not stated in full report

      Complete case prose and the treatment timeline specify dose and schedule but do not state the actual administration route; a cited trial schedule is not patient-specific route verification.

    • MacitentanOral

      The report identifies this ERA/PDE5-inhibitor regimen as the initial oral combination; macitentan 10 mg daily.

    • TadalafilOral

      The report identifies this ERA/PDE5-inhibitor regimen as the initial oral combination; tadalafil 40 mg daily.

    Explore trial report
  • HYPERION · 2025Controlled report · Tested therapy · Sotatercept · Positive primary endpointRouteSotatercept: subcutaneous (SC) injection

    Events in 10.6% versus 36.9%; HR 0.24 (95% CI 0.14–0.41). Deaths were 7 versus 6.

    Route of administration

    • Sotaterceptsubcutaneous (SC) injection
    Explore trial report
  • Sotatercept · pooled long-term safety · 2025Conference report · Tested therapy · Sotatercept · Secondary report · no separate primary comparisonRouteSotatercept: subcutaneous (SC) injection

    Exposure totaled 1,206 person-years, median 2.5 years and maximum 6.2 years. Reported rates of serious events, serious bleeding, epistaxis, hemoglobin elevation, thrombocytopenia and thrombosis were generally stable across cutoffs.

    Route of administration

    • Sotaterceptsubcutaneous (SC) injection
    Explore trial report
  • SOTERIA · updated conference follow-up · 2025Conference report · Tested therapy · Sotatercept · No confirmatory primary comparisonRouteSotatercept: subcutaneous (SC) injection

    Serious treatment-related events affected 30/480 (6%), including serious bleeding in 17 (4%). Adverse events led to study discontinuation in 33 (7%). Clinical worsening affected 45 (9%), including 21 deaths; functional improvements were generally maintained among observed participants.

    Route of administration

    • Sotaterceptsubcutaneous (SC) injection
    Explore trial report
  • SOTERIA interim · 2025Extension study · Tested therapy · Sotatercept · No confirmatory primary comparisonRouteSotatercept: subcutaneous (SC) injection

    Mean exposure approximately 449 days; efficacy measures were largely maintained at one year. Serious bleeding occurred in 22 participants (5.2%).

    Route of administration

    • Sotaterceptsubcutaneous (SC) injection
    Explore trial report
  • STELLAR / SOTERIA · survival analysis · 2025Conference report · Tested therapy · Sotatercept · Secondary report · no separate primary comparisonRouteSotatercept: subcutaneous (SC) injection

    There were 3 deaths in the original sotatercept group and 11 in the original placebo group. The crossover-adjusted mortality HR was 0.17 (95% CI 0.03–0.90).

    Route of administration

    • Sotaterceptsubcutaneous (SC) injection
    Explore trial report
  • ZENITH · 2025Controlled report · Tested therapy · Sotatercept · Positive primary endpointRouteSotatercept: subcutaneous (SC) injection

    Primary events in 17.4% versus 54.7%; HR 0.24 (95% CI 0.13–0.43). Deaths were 7 versus 13.

    Route of administration

    • Sotaterceptsubcutaneous (SC) injection
    Explore trial report
  • SPECTRA · 2024Single-arm study · Tested therapy · Sotatercept · No confirmatory primary comparisonRouteSotatercept: subcutaneous (SC) injection

    Peak oxygen uptake increased 102.74 mL/min from baseline (95% CI 27.72–177.76), with favorable hemodynamic and RV measurements.

    Route of administration

    • Sotaterceptsubcutaneous (SC) injection
    Explore trial report
  • PULSAR open-label extension · 2023Extension study · Tested therapy · Sotatercept · No confirmatory primary comparisonRouteSotatercept: subcutaneous (SC) injection

    PVR, walking distance and functional class improved after crossover and were generally maintained with continued treatment. Serious adverse events occurred in 32/104 (30.8%); 10/104 (9.6%) discontinued for treatment-emergent events. Three deaths occurred, none investigator-attributed to treatment.

    Route of administration

    • Sotaterceptsubcutaneous (SC) injection
    Explore trial report
  • STELLAR · 2023Controlled report · Tested therapy · Sotatercept · Positive primary endpointRouteSotatercept: subcutaneous (SC) injection

    Hodges–Lehmann treatment difference +40.8 m (95% CI 27.5–54.1); several hierarchically tested secondary endpoints also improved.

    Route of administration

    • Sotaterceptsubcutaneous (SC) injection
    Explore trial report
  • STELLAR · haemodynamics and right-heart function · 2023Controlled report · Tested therapy · Sotatercept · Secondary report · no separate primary comparisonRouteSotatercept: subcutaneous (SC) injection

    Placebo-adjusted mPAP fell 13.9 mmHg, PVR 254.8 dyn·s/cm⁵ and RAP 2.7 mmHg; RV size and TAPSE/sPAP improved. TAPSE alone, cardiac output and stroke volume did not significantly differ.

    Route of administration

    • Sotaterceptsubcutaneous (SC) injection
    Explore trial report
  • PULSAR · 2021Controlled report · Tested therapy · Sotatercept · Positive primary endpointRouteSotatercept: subcutaneous (SC) injection

    Placebo-adjusted PVR −145.8 dyn·s·cm⁻⁵ (95% CI −241.0 to −50.6) at 0.3 mg/kg and −239.5 (−329.3 to −149.7) at 0.7 mg/kg.

    Route of administration

    • Sotaterceptsubcutaneous (SC) injection
    Explore trial report
Use of sotatercept in an adolescent patient with idiopathic pulmonary arterial hypertension · 2026A044 HYPERION · RV echo secondary report · PVRI 2026 Dublin · 2026Sotatercept in Pediatric Pulmonary Hypertension: Experience from the Pediatric Pulmonary Hypertension Network · 2026Off-Label Sotatercept Use in Pediatric Pulmonary Arterial Hypertension: A Single-Center Retrospective Hemodynamic Study · 2026First Report of Real World Utilization of an Activin Signaling Inhibitor in Patients With Severe Pulmonary Arterial Hypertension in the Middle East PH RISE-ME Study · 2026A156 Sotatercept in High-Risk PAH Patients Under Triple Combination Therapy, in a Greek PAH centre · PVRI 2026 Dublin · 2026Phase 3, Open-Label Multicenter Study of Sotatercept in Japanese Participants With Pulmonary Arterial Hypertension · 2026A010 Sotatercept · Ohio State first-year practice · PVRI 2026 Dublin · 2026Novel cardiovascular magnetic resonance imaging biomarkers to track response to treatment including Sotatercept in a patient with idiopathic pulmonary arterial hypertension: a case report · 2026Sotatercept-related peripheral microvascular alterations in systemic sclerosis-associated pulmonary arterial hypertension: insights from nailfold capillaroscopy. · 2026A170 Sotatercept · two Eisenmenger cases · PVRI 2026 Dublin · 2026A175 Sotatercept · two-center US experience · PVRI 2026 Dublin · 2026Sotatercept as a Treatment for Pulmonary Hypertension Associated With Connective Tissue Disease and ILD · 2026Salvage Use of Sotatercept for Potts Shunt in Refractory Pulmonary Hypertension · 2026Case Report: Upfront sotatercept-based triple therapy in high-risk systemic sclerosis-associated pulmonary arterial hypertension · 2026Sotatercept for Pulmonary Arterial Hypertension within the First Year after Diagnosis (HYPERION) · 2025Pooled sotatercept long-term safety (ATS abstract) · 2025SOTERIA updated long-term follow-up (ERS abstract) · 2025A long-term follow-up study of sotatercept for treatment of pulmonary arterial hypertension: interim results of SOTERIA · 2025STELLAR / SOTERIA survival analysis (ATS abstract) · 2025Sotatercept in Patients with Pulmonary Arterial Hypertension at High Risk for Death (ZENITH) · 2025SPECTRA Phase 2b Study: Impact of Sotatercept on Exercise Tolerance and Right Ventricular Function in Pulmonary Arterial Hypertension · 2024PULSAR open-label extension · 2023Phase 3 Trial of Sotatercept for Treatment of Pulmonary Arterial Hypertension (STELLAR) · 2023Effects of sotatercept on haemodynamics and right heart function: analysis of the STELLAR trial · 2023Sotatercept for the Treatment of Pulmonary Arterial Hypertension (PULSAR) · 2021European Respiratory Society clinical practice guidelines update for the treatment of pulmonary arterial hypertension (accepted Early View version) · 2026Treatment algorithm for pulmonary arterial hypertension · 2024
Other indexed classes (29)

These entries remain unscored. Missing or indirect evidence does not establish absence of benefit or harm.

  • ACE inhibition / angiotensin receptor blockadeNo reviewed overall benefit–risk assessment for this class in the selected PH group. Individual report findings and warnings remain available.Explore reports
  • Alpha-1 adrenergic blockadeNo reviewed overall benefit–risk assessment for this class in the selected PH group. Individual report findings and warnings remain available.Explore reports
  • Angiotensin-converting enzyme inhibitionNo reviewed overall benefit–risk assessment for this class in the selected PH group. Individual report findings and warnings remain available.Explore reports
  • Anti-VEGF exposure safetyNo reviewed overall benefit–risk assessment for this class in the selected PH group. Individual report findings and warnings remain available.Explore reports
  • AnticoagulationNo reviewed overall benefit–risk assessment for this class in the selected PH group. Individual report findings and warnings remain available.Explore reports
  • Antiplatelet therapyNo reviewed overall benefit–risk assessment for this class in the selected PH group. Individual report findings and warnings remain available.Explore reports
  • Apelin receptor agonismNo reviewed overall benefit–risk assessment for this class in the selected PH group. Individual report findings and warnings remain available.Explore reports
  • Aromatase inhibitionNo reviewed overall benefit–risk assessment for this class in the selected PH group. Individual report findings and warnings remain available.Explore reports
  • Beta blockadeNo reviewed overall benefit–risk assessment for this class in the selected PH group. Individual report findings and warnings remain available.Explore reports
  • Historical potassium-channel openingNo reviewed overall benefit–risk assessment for this class in the selected PH group. Individual report findings and warnings remain available.Explore reports
  • Immune / BMPR2-targeted approachesNo reviewed overall benefit–risk assessment for this class in the selected PH group. Individual report findings and warnings remain available.Explore reports
  • Inhaled nitric oxideNo reviewed overall benefit–risk assessment for this class in the selected PH group. Individual report findings and warnings remain available.Explore reports
  • Iron replacementNo reviewed overall benefit–risk assessment for this class in the selected PH group. Individual report findings and warnings remain available.Explore reports
  • Leukotriene A4 hydrolase inhibitionNo reviewed overall benefit–risk assessment for this class in the selected PH group. Individual report findings and warnings remain available.Explore reports
  • Metabolic / RV energetics approachesNo reviewed overall benefit–risk assessment for this class in the selected PH group. Individual report findings and warnings remain available.Explore reports
  • Micronutrient deficiency treatmentNo reviewed overall benefit–risk assessment for this class in the selected PH group. Individual report findings and warnings remain available.Explore reports
  • Mineralocorticoid receptor antagonismNo reviewed overall benefit–risk assessment for this class in the selected PH group. Individual report findings and warnings remain available.Explore reports
  • Nrf2 / oxidative-stress modulationNo reviewed overall benefit–risk assessment for this class in the selected PH group. Individual report findings and warnings remain available.Explore reports
  • Organic nitrate vasodilationNo reviewed overall benefit–risk assessment for this class in the selected PH group. Individual report findings and warnings remain available.Explore reports
  • PARP inhibitionNo reviewed overall benefit–risk assessment for this class in the selected PH group. Individual report findings and warnings remain available.Explore reports
  • Prostanoid therapy · agent unspecifiedNo reviewed overall benefit–risk assessment for this class in the selected PH group. Individual report findings and warnings remain available.Explore reports
  • Recombinant ACE2 / renin–angiotensin modulationNo reviewed overall benefit–risk assessment for this class in the selected PH group. Individual report findings and warnings remain available.Explore reports
  • Rho-kinase inhibitionNo reviewed overall benefit–risk assessment for this class in the selected PH group. Individual report findings and warnings remain available.Explore reports
  • Serotonin synthesis inhibitionNo reviewed overall benefit–risk assessment for this class in the selected PH group. Individual report findings and warnings remain available.Explore reports
  • Serotonin transporter inhibitionNo reviewed overall benefit–risk assessment for this class in the selected PH group. Individual report findings and warnings remain available.Explore reports
  • SGLT2 inhibitors / HF filling-pressure therapyNo reviewed overall benefit–risk assessment for this class in the selected PH group. Individual report findings and warnings remain available.Explore reports
  • StatinsNo reviewed overall benefit–risk assessment for this class in the selected PH group. Individual report findings and warnings remain available.Explore reports
  • Supplemental oxygenNo reviewed overall benefit–risk assessment for this class in the selected PH group. Individual report findings and warnings remain available.Explore reports
  • Thromboxane inhibitionNo reviewed overall benefit–risk assessment for this class in the selected PH group. Individual report findings and warnings remain available.Explore reports
Reports needing indexing review (3)
  • Severe pediatric PH · four PICU treatment coursesPH group unresolved: Mixed pediatric etiologies and incomplete invasive phenotyping prevent verified clinical-group assignment for this four-patient cohort.
  • Diazoxide · three-patient acute harm reportPH group unresolved: The historical PH abstract does not expose sufficient etiologic or invasive detail to assign a modern clinical group.
  • Hydralazine-associated lupus/PH · withdrawal casePH group unresolved: Historical lupus-associated PH with possible thromboembolic disease and later left-heart failure; a single modern group cannot be assigned from this report.
How to read this figure

This is an editorial overview of benefit, harm, applicability and uncertainty in the selected population. A favorable category still requires patient selection and safety monitoring. “Mixed” retains conflicting drugs, routes or populations within an entry.

The indexed studies measure different outcomes over different periods. Their results cannot supply a common clinical benefit:risk ratio. We do not divide positive studies by harm reports, pool effect sizes, or infer safety when adverse-event data are missing.

Classes retain their individual drugs and limitations. Combination findings, comparator roles and adjacent populations stay identified in the report details. New or insufficiently reviewed entries remain unscored.

Model reference & review methodFDA · benefit–risk frameworkCochrane · interpreting treatment effects
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