title: Identifying determinants of variability to tailor aspirin therapy.
abstract: Once-daily, low-dose aspirin is a cornerstone in the prophylaxis and treatment of cardiovascular diseases. Aspirin 'resistance' still lacks definition, a standardized reference assay, underlying mechanisms, clinical impact or efficacy of alternative antiplatelet drugs. Aspirin response in several studies has been measured by different platelet function tests, not always reflecting aspirin pharmacodynamics, thus generating significantly heterogeneous results. The EMA indicated serum thromboxane B2 as the only valid surrogate assay to study different aspirin formulations. Rather than resistance, recent studies focused on sources of intra- and inter-individual variability in response to aspirin, based on pharmacokinetic and/or pharmacodynamic mechanisms. Drug interactions, diabetes, conditions of increased platelet output, obesity and aging can potentially increase the variability of aspirin response. Preliminary studies testing different aspirin regimens showed that twice-daily low doses were more effective than once-daily higher aspirin doses on surrogate end points of platelet inhibition. Large studies are needed to test new disease-tailored, low-dose aspirin regimens.
authors.affiliation: Department of Pharmacology, Catholic University School of Medicine, Rome, Italy. b.rocca@tiscali.it
authors.forename: Bianca
authors.initials: B
authors.lastname: Rocca
authors.forename: Alfredo
authors.initials: A
authors.lastname: Dragani
authors.forename: Francesca
authors.initials: F
authors.lastname: Pagliaccia
mesh_terms: D000818:Animals; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001792:Blood Platelets / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004351:Drug Resistance; D006801:Humans; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D010979:Platelet Function Tests
chemical_list: D010975:Platelet Aggregation Inhibitors; D001241:Aspirin