{"id":"4eab25b2-a423-5b27-911d-2b39807af291","stable_key":"8ccb5461-efe2-5d95-9869-950d7cd50575:tadalafil-six-minute-walk-in-pulmonary-arterial-hypertension","predicate":"increases","statement":"Tadalafil increased six-minute walk distance in a dose-dependent manner in pulmonary arterial hypertension, with a mean placebo-corrected effect of 33 metres, and only the 40 mg dose met the prespecified level of statistical significance.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"6ce42533-e68c-5c44-9d3a-573832f85960","mechanism_event_label":"Tadalafil increased six-minute walk distance in a dose-dependent manner in pulmonary arterial hypertension, with a mean placebo-corrected effect of 33 metres, and only the 40 mg dose met the prespecified level of statistical significance.","subject":{"id":"9820ebfe-515d-50cc-9b44-2bd2be220325","slug":"tadalafil","display_name":"Tadalafil","entity_type_key":"drug"},"object":{"id":"c0eba152-bcc3-5e47-9d7d-b06f2ddcb105","slug":"six-minute-walk-distance","display_name":"Six-minute walk distance","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"6ce42533-e68c-5c44-9d3a-573832f85960","stable_key":"8ccb5461-efe2-5d95-9869-950d7cd50575:tadalafil-six-minute-walk-in-pulmonary-arterial-hypertension-event","event_type":"observed_relationship","label":"Tadalafil increased six-minute walk distance in a dose-dependent manner in pulmonary arterial hypertension, with a mean placebo-corrected effect of 33 metres, and only the 40 mg dose met the prespecified level of statistical significance.","description":"Tadalafil increased six-minute walk distance in a dose-dependent manner in pulmonary arterial hypertension, with a mean placebo-corrected effect of 33 metres, and only the 40 mg dose met the prespecified level of statistical significance.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"9820ebfe-515d-50cc-9b44-2bd2be220325","slug":"tadalafil","display_name":"Tadalafil","entity_type_key":"drug"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"c0eba152-bcc3-5e47-9d7d-b06f2ddcb105","slug":"six-minute-walk-distance","display_name":"Six-minute walk distance","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"d19d1993-e1dc-5e7e-864c-8a90ccf0905a","slug":"bosentan","display_name":"Bosentan","entity_type_key":"drug"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"6d2f509b-3a5b-5a38-b3e7-b148581edec9","slug":"cgmp","display_name":"Cyclic guanosine monophosphate","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"duration","value_text":"16 weeks, double-blind placebo-controlled","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_access","value_text":"Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"405 patients with idiopathic or associated pulmonary arterial hypertension, treatment-naive or on background bosentan","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Tadalafil 2.5, 10, 20 or 40 mg once daily against placebo","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"The treatment effect was 44 metres in bosentan-naive patients and 23 metres with confidence intervals crossing zero in those already on bosentan, so the benefit on top of existing endothelin blockade was not established here. PubMed records an erratum for this paper without a resolvable identifier, so the erratum was not read and it is not known whether it altered these figures.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"organism","value_text":"405 patients with idiopathic or associated pulmonary arterial hypertension, treatment-naive or on background bosentan","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Tadalafil increased six-minute walk distance in a dose-dependent manner in pulmonary arterial hypertension, with a mean placebo-corrected effect of 33 metres, and only the 40 mg dose met the prespecified level of statistical significance.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Tadalafil therapy for pulmonary arterial hypertension. (2009). https://pubmed.ncbi.nlm.nih.gov/19470885/ DOI: 10.1161/CIRCULATIONAHA.108.839274","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"route","value_text":"Oral","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue","value_text":"Six-minute walk distance, WHO functional class and clinical worsening","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"0e5b28b8-4291-5d04-935e-b5a553b77428","evidence_kind":"source_excerpt","locator":"Lines 100-109","start_line":100,"end_line":109,"excerpt":"## tadalafil-six-minute-walk-in-pulmonary-arterial-hypertension\nTadalafil increased six-minute walk distance in a dose-dependent manner in pulmonary arterial hypertension, with a mean placebo-corrected effect of 33 metres, and only the 40 mg dose met the prespecified level of statistical significance.\nModel/species: 405 patients with idiopathic or associated pulmonary arterial hypertension, treatment-naive or on background bosentan\nTissue/system: Six-minute walk distance, WHO functional class and clinical worsening\nExposure: Tadalafil 2.5, 10, 20 or 40 mg once daily against placebo\nRoute: Oral\nDuration: 16 weeks, double-blind placebo-controlled\nLimits: The treatment effect was 44 metres in bosentan-naive patients and 23 metres with confidence intervals crossing zero in those already on bosentan, so the benefit on top of existing endothelin blockade was not established here. PubMed records an erratum for this paper without a resolvable identifier, so the erratum was not read and it is not known whether it altered these figures.\nPrimary reference: Tadalafil therapy for pulmonary arterial hypertension. (2009). https://pubmed.ncbi.nlm.nih.gov/19470885/ DOI: 10.1161/CIRCULATIONAHA.108.839274\nAccess: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.","model_system":"","directness":"reported_statement","verification_status":"source_derived_draft","notes":"","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"cca24ae7-e036-525c-a440-4cc2e38ccb4d","stable_key":"import-8ccb5461-efe2-5d95-9869-950d7cd50575","title":"Tadalafil: PDE5 occupancy, the cGMP route and three measured endpoints (2026-09-22)","document_type":"imported_text","citation_label":"Original AI-assisted curation of seven primary studies resolved by PubMed title search, with every abstract read and all DOIs cross-checked against live PubMed metadata. Two references carry an unresolvable erratum and are recorded as corrected. Study-specific doses, effect sizes and limitations retained. 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