{"id":"0d55c276-bc74-585e-954e-573cbf493dc4","stable_key":"0a5134ca-a214-59b8-8017-f89b299ace92:simvastatin-dose-raises-myopathy","predicate":"increases","statement":"Myopathy occurred in 2 of 6,033 participants taking 20 mg simvastatin daily and in 53 of 6,031 taking 80 mg daily.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"dea02d20-0c78-5940-a521-a339649514a7","mechanism_event_label":"Myopathy occurred in 2 of 6,033 participants taking 20 mg simvastatin daily and in 53 of 6,031 taking 80 mg daily.","subject":{"id":"2bbd9611-c1e2-5269-909c-a3ae4e797485","slug":"simvastatin-80mg-daily","display_name":"Simvastatin 80 mg daily","entity_type_key":"cellular_process"},"object":{"id":"6d822dfd-c22c-594d-9660-a539e8b22759","slug":"statin-muscle-pain","display_name":"Statin-associated muscle pain","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"dea02d20-0c78-5940-a521-a339649514a7","stable_key":"0a5134ca-a214-59b8-8017-f89b299ace92:simvastatin-dose-raises-myopathy-event","event_type":"observed_relationship","label":"Myopathy occurred in 2 of 6,033 participants taking 20 mg simvastatin daily and in 53 of 6,031 taking 80 mg daily.","description":"Myopathy occurred in 2 of 6,033 participants taking 20 mg simvastatin daily and in 53 of 6,031 taking 80 mg daily.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"2bbd9611-c1e2-5269-909c-a3ae4e797485","slug":"simvastatin-80mg-daily","display_name":"Simvastatin 80 mg daily","entity_type_key":"cellular_process"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"6d822dfd-c22c-594d-9660-a539e8b22759","slug":"statin-muscle-pain","display_name":"Statin-associated muscle pain","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"8e29fed8-9977-5dbe-b8bb-264a928d1027","slug":"simvastatin-20mg-daily","display_name":"Simvastatin 20 mg daily","entity_type_key":"cellular_process"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"b7de977d-fed9-5b1c-8138-fd951442b067","slug":"simvastatin","display_name":"Simvastatin","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"duration","value_text":"Mean follow-up 6.7 years","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":"12,064 men and women aged 18-80 with a history of myocardial infarction","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"80 mg versus 20 mg simvastatin daily, randomised double-blind","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Dose is the randomised variable, not measured plasma concentration; the trial's primary endpoint was major vascular events and myopathy was a safety outcome. The trial was funded by the drug's manufacturer.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"organism","value_text":"12,064 men and women aged 18-80 with a history of myocardial infarction","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Myopathy occurred in 2 of 6,033 participants taking 20 mg simvastatin daily and in 53 of 6,031 taking 80 mg daily.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Intensive lowering of LDL cholesterol with 80 mg versus 20 mg simvastatin daily in 12,064 survivors of myocardial infarction: a double-blind randomised trial. (2010). https://pubmed.ncbi.nlm.nih.gov/21067805/ DOI: 10.1016/S0140-6736(10)60310-8","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"route","value_text":"Oral","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue","value_text":"Myopathy as an adverse outcome","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"906a9fc8-606c-558d-98e4-23b8a4e34f29","evidence_kind":"source_excerpt","locator":"Lines 13-22","start_line":13,"end_line":22,"excerpt":"## simvastatin-dose-raises-myopathy\nMyopathy occurred in 2 of 6,033 participants taking 20 mg simvastatin daily and in 53 of 6,031 taking 80 mg daily.\nModel/species: 12,064 men and women aged 18-80 with a history of myocardial infarction\nTissue/system: Myopathy as an adverse outcome\nExposure: 80 mg versus 20 mg simvastatin daily, randomised double-blind\nRoute: Oral\nDuration: Mean follow-up 6.7 years\nLimits: Dose is the randomised variable, not measured plasma concentration; the trial's primary endpoint was major vascular events and myopathy was a safety outcome. The trial was funded by the drug's manufacturer.\nPrimary reference: Intensive lowering of LDL cholesterol with 80 mg versus 20 mg simvastatin daily in 12,064 survivors of myocardial infarction: a double-blind randomised trial. (2010). https://pubmed.ncbi.nlm.nih.gov/21067805/ DOI: 10.1016/S0140-6736(10)60310-8\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":"6e42a53a-5f31-5a81-87ba-a3edc49aface","stable_key":"import-0a5134ca-a214-59b8-8017-f89b299ace92","title":"Statin plasma exposure and muscle injury: dose randomisation and a drug interaction (2026-09-22)","document_type":"imported_text","citation_label":"Original AI-assisted curation of three primary studies resolved by PubMed title search and cross-checked against live PubMed metadata. Two share a research group with the OATP1B1 collection and are recorded as one line of evidence with it. Study-specific doses, effect sizes and limitations retained. Not publisher full text.","file_path":"","sha256":"33f81004d0b40ff01b3cc13113ba2991833a171a7a535fdf1c2d3c015f9f7b1c","revision_id":"3ccfa03e-b7ed-5569-9e22-af3e5de65955","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}