{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T18:56:04Z","timestamp":1791831364734,"version":"4.3.4"},"reference-count":35,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"25","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2009,12,22]]},"abstract":"<jats:p>\n            <jats:bold>\n              <jats:italic>Background\u2014<\/jats:italic>\n            <\/jats:bold>\n            Poor clinical outcome in aspirin-treated patients has been termed\n            <jats:italic>aspirin resistance<\/jats:italic>\n            and may result from inadequate inhibition of platelet cyclooxygenase-1 (COX-1) by aspirin. The objectives of this study were to determine prospectively whether COX-1-dependent and other platelet function assays correlate with clinical outcomes in aspirin-treated patients.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Methods and Results\u2014<\/jats:italic>\n            <\/jats:bold>\n            Blood was collected before percutaneous coronary intervention from 700 consecutive aspirin-treated (81 or 325 mg for \u22653 days) patients. Platelet function was tested by (1) serum thromboxane B\n            <jats:sub>2<\/jats:sub>\n            ; (2) arachidonic acid-stimulated platelet surface P-selectin and activated glycoprotein IIb\/IIIa and leukocyte-platelet aggregates; and (3) platelet function analyzer (PFA)-100 collagen-epinephrine and collagen-ADP closure time (CT). Adverse clinical outcomes of all-cause death, cardiovascular death, and major adverse cardiovascular events (cardiovascular death, myocardial infarction, hospitalization for revascularization, or acute coronary syndrome) were assessed by telephone interview and\/or medical record review. Clinical outcomes information was obtained at 24.8\u00b10.3 months after platelet function testing. By univariate analysis, COX-1-dependent assays, including serum thromboxane B\n            <jats:sub>2<\/jats:sub>\n            level, were not associated with adverse clinical outcomes, whereas the COX-1-independent assay, PFA-100 collagen-ADP CT &lt;65 seconds, was associated with major adverse cardiovascular events (\n            <jats:italic>P<\/jats:italic>\n            =0.0149). After adjustment for covariables (including sex, aspirin dose, Thrombolysis in Myocardial Infarction risk score, clopidogrel use), both serum thromboxane B\n            <jats:sub>2<\/jats:sub>\n            &gt;3.1 ng\/mL and PFA-100 collagen-ADP CT &lt;65 seconds were associated with major adverse cardiovascular events. In contrast, indirect measures of platelet COX-1 (arachidonic acid-stimulated platelet markers, shortened PFA-100 collagen-epinephrine CT) were not significantly associated with adverse clinical outcomes even after adjustment for covariables.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Conclusions\u2014<\/jats:italic>\n            <\/jats:bold>\n            In this prospective study of 700 aspirin-treated patients presenting for angiographic evaluation of coronary artery disease, residual platelet COX-1 function measured by serum thromboxane B\n            <jats:sub>2<\/jats:sub>\n            and COX-1-independent platelet function measured by PFA-100 collagen-ADP CT, but not indirect COX-1-dependent assays (arachidonic acid-stimulated platelet markers, shortened PFA-100 collagen-epinephrine CT), correlate with subsequent major adverse cardiovascular events. This study suggests that multiple mechanisms, including but not confined to inadequate inhibition of COX-1, are responsible for poor clinical outcomes in aspirin-treated patients, and therefore the term\n            <jats:italic>aspirin resistance<\/jats:italic>\n            is inappropriate.\n          <\/jats:p>","DOI":"10.1161\/circulationaha.109.900589","type":"journal-article","created":{"date-parts":[[2009,12,8]],"date-time":"2009-12-08T05:32:37Z","timestamp":1260250357000},"page":"2586-2596","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":155,"title":["Association of Cyclooxygenase-1-Dependent and -Independent Platelet Function Assays With Adverse Clinical Outcomes in Aspirin-Treated Patients Presenting for Cardiac Catheterization"],"prefix":"10.1161","volume":"120","author":[{"suffix":"III","given":"Andrew L.","family":"Frelinger","sequence":"first","affiliation":[{"name":"From the Center for Platelet Function Studies, Departments of Pediatrics and Medicine, University of Massachusetts Medical School, Worcester (A.L.F., Y.L., M.D.L., M.R.B., M.L.F., M.I.F., A.D.M.); Center for Platelet Research Studies, Division of Hematology\/Oncology, Children\u2019s Hospital Boston, Harvard Medical School, Boston, Mass (A.L.F., M.R.B., A.D.M.); Siemens Healthcare Diagnostics, Newark, Del (D.J.C.); and South Shore Hospital, South Weymouth, Mass (M.I.F.). Dr Linden is currently affiliated..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"YouFu","family":"Li","sequence":"additional","affiliation":[{"name":"From the Center for Platelet Function Studies, Departments of Pediatrics and Medicine, University of Massachusetts Medical School, Worcester (A.L.F., Y.L., M.D.L., M.R.B., M.L.F., M.I.F., A.D.M.); Center for Platelet Research Studies, Division of Hematology\/Oncology, Children\u2019s Hospital Boston, Harvard Medical School, Boston, Mass (A.L.F., M.R.B., A.D.M.); Siemens Healthcare Diagnostics, Newark, Del (D.J.C.); and South Shore Hospital, South Weymouth, Mass (M.I.F.). Dr Linden is currently affiliated..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew D.","family":"Linden","sequence":"additional","affiliation":[{"name":"From the Center for Platelet Function Studies, Departments of Pediatrics and Medicine, University of Massachusetts Medical School, Worcester (A.L.F., Y.L., M.D.L., M.R.B., M.L.F., M.I.F., A.D.M.); Center for Platelet Research Studies, Division of Hematology\/Oncology, Children\u2019s Hospital Boston, Harvard Medical School, Boston, Mass (A.L.F., M.R.B., A.D.M.); Siemens Healthcare Diagnostics, Newark, Del (D.J.C.); and South Shore Hospital, South Weymouth, Mass (M.I.F.). Dr Linden is currently affiliated..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc R.","family":"Barnard","sequence":"additional","affiliation":[{"name":"From the Center for Platelet Function Studies, Departments of Pediatrics and Medicine, University of Massachusetts Medical School, Worcester (A.L.F., Y.L., M.D.L., M.R.B., M.L.F., M.I.F., A.D.M.); Center for Platelet Research Studies, Division of Hematology\/Oncology, Children\u2019s Hospital Boston, Harvard Medical School, Boston, Mass (A.L.F., M.R.B., A.D.M.); Siemens Healthcare Diagnostics, Newark, Del (D.J.C.); and South Shore Hospital, South Weymouth, Mass (M.I.F.). Dr Linden is currently affiliated..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marsha L.","family":"Fox","sequence":"additional","affiliation":[{"name":"From the Center for Platelet Function Studies, Departments of Pediatrics and Medicine, University of Massachusetts Medical School, Worcester (A.L.F., Y.L., M.D.L., M.R.B., M.L.F., M.I.F., A.D.M.); Center for Platelet Research Studies, Division of Hematology\/Oncology, Children\u2019s Hospital Boston, Harvard Medical School, Boston, Mass (A.L.F., M.R.B., A.D.M.); Siemens Healthcare Diagnostics, Newark, Del (D.J.C.); and South Shore Hospital, South Weymouth, Mass (M.I.F.). Dr Linden is currently affiliated..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas J.","family":"Christie","sequence":"additional","affiliation":[{"name":"From the Center for Platelet Function Studies, Departments of Pediatrics and Medicine, University of Massachusetts Medical School, Worcester (A.L.F., Y.L., M.D.L., M.R.B., M.L.F., M.I.F., A.D.M.); Center for Platelet Research Studies, Division of Hematology\/Oncology, Children\u2019s Hospital Boston, Harvard Medical School, Boston, Mass (A.L.F., M.R.B., A.D.M.); Siemens Healthcare Diagnostics, Newark, Del (D.J.C.); and South Shore Hospital, South Weymouth, Mass (M.I.F.). Dr Linden is currently affiliated..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark I.","family":"Furman","sequence":"additional","affiliation":[{"name":"From the Center for Platelet Function Studies, Departments of Pediatrics and Medicine, University of Massachusetts Medical School, Worcester (A.L.F., Y.L., M.D.L., M.R.B., M.L.F., M.I.F., A.D.M.); Center for Platelet Research Studies, Division of Hematology\/Oncology, Children\u2019s Hospital Boston, Harvard Medical School, Boston, Mass (A.L.F., M.R.B., A.D.M.); Siemens Healthcare Diagnostics, Newark, Del (D.J.C.); and South Shore Hospital, South Weymouth, Mass (M.I.F.). Dr Linden is currently affiliated..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan D.","family":"Michelson","sequence":"additional","affiliation":[{"name":"From the Center for Platelet Function Studies, Departments of Pediatrics and Medicine, University of Massachusetts Medical School, Worcester (A.L.F., Y.L., M.D.L., M.R.B., M.L.F., M.I.F., A.D.M.); Center for Platelet Research Studies, Division of Hematology\/Oncology, Children\u2019s Hospital Boston, Harvard Medical School, Boston, Mass (A.L.F., M.R.B., A.D.M.); Siemens Healthcare Diagnostics, Newark, Del (D.J.C.); and South Shore Hospital, South Weymouth, Mass (M.I.F.). 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