title: Predictors of high on-aspirin platelet reactivity in high-risk vascular patients treated with single or dual antiplatelet therapy.
abstract: Aspirin is the key treatment in the secondary prevention of atherothrombosis. Interindividual variability of response has been linked to a higher risk for ischemic events. The aim of this study was to identify clinical and biologic factors predicting high on-aspirin platelet reactivity (HPR) in a high-risk, "real-world" population of vascular patients. All platelet testing performed from 2011 to 2013 in consecutive patients receiving long-term treatment with aspirin for coronary or cerebrovascular disease was retrospectively analyzed. Indications for platelet testing were recurrent ischemic events or high-risk angioplasty. HPR was defined as aggregation intensity≥20% using light-transmission aggregometry with arachidonic acid 0.5 mg/ml. Collagen-epinephrine platelet function analysis was also performed (threshold<165 seconds). Cardiovascular risk factors, usual biologic parameters, and antiplatelet treatment were recorded. A total of 1,508 patients were included (mean age 63 years, 71% men, 23% with diabetes). Antiplatelet treatment was aspirin alone in 333 patients and dual-antiplatelet therapy in 1,175 patients. HPR was found in 11.1% of patients. In multivariate analysis, independent predictive factors of HPR on light-transmission aggregometry with arachidonic acid were diabetes mellitus (odds ratio [OR] 2.10, 95% confidence interval [CI] 1.39 to 3.16), age (OR 1.25, 95% CI 1.06 to 1.47), fibrinogen level (OR 1.20, 95% CI 1.02 to 1.42), and von Willebrand factor level (OR 1.06, 95% CI 1.03 to 1.09). On light-transmission aggregometry with arachidonic acid and collagen-epinephrine platelet function analysis, fibrinogen remained the main factor associated with HPR (OR 1.33, 95% CI 1.19 to 1.61). Similar results were found in patients treated with aspirin alone or dual-antiplatelet therapy. A fibrinogen level>4.0 g/L was associated with a 3.9-fold increased risk for HPR in patients aged <75 years. In conclusion, fibrinogen level was the major predictor of HPR on aspirin in this large population of high-risk vascular patients.
authors.affiliation: Department of Cardiology, Inserm U942, Lariboisiere Hospital, AP-HP, Paris Diderot University, Paris, France. Electronic address: myriam.amsallem@gmail.com.
authors.forename: Myriam
authors.initials: M
authors.lastname: Amsallem
authors.affiliation: Department of Cardiology, Inserm U942, Lariboisiere Hospital, AP-HP, Paris Diderot University, Paris, France.
authors.forename: Stephane
authors.initials: S
authors.lastname: Manzo-Silberman
authors.affiliation: Department of Cardiology, Inserm U942, Lariboisiere Hospital, AP-HP, Paris Diderot University, Paris, France.
authors.forename: Jean-Guillaume
authors.initials: JG
authors.lastname: Dillinger
authors.affiliation: Department of Cardiology, Inserm U942, Lariboisiere Hospital, AP-HP, Paris Diderot University, Paris, France.
authors.forename: Georgios
authors.initials: G
authors.lastname: Sideris
authors.affiliation: Department of Cardiology, Inserm U942, Lariboisiere Hospital, AP-HP, Paris Diderot University, Paris, France.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Voicu
authors.affiliation: Department of Angio-Hematology and IVS-Lariboisiere Hospital, AP-HP, Paris Diderot University, Paris, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Bal dit Sollier
authors.affiliation: Department of Angio-Hematology and IVS-Lariboisiere Hospital, AP-HP, Paris Diderot University, Paris, France.
authors.forename: Ludovic
authors.initials: L
authors.lastname: Drouet
authors.affiliation: Department of Cardiology, Inserm U942, Lariboisiere Hospital, AP-HP, Paris Diderot University, Paris, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Henry
mesh_terms: D000241:Adenosine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000368:Aged; D001241:Aspirin / Q000008:administration & dosage*; D002561:Cerebrovascular Disorders / Q000097:blood / Q000517:prevention & control*; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000097:blood / Q000517:prevention & control*; D004359:Drug Therapy, Combination; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage; D015539:Platelet Activation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D000068799:Prasugrel Hydrochloride; D011237:Predictive Value of Tests; D058921:Purinergic P2Y Receptor Antagonists / Q000008:administration & dosage; D012189:Retrospective Studies; D055502:Secondary Prevention; D013876:Thiophenes / Q000008:administration & dosage; D000077486:Ticagrelor; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D013876:Thiophenes; D005340:Fibrinogen; D000077144:Clopidogrel; D000068799:Prasugrel Hydrochloride; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine; D001241:Aspirin