title: Effects of P2Y12 receptor inhibition with or without aspirin on hemostatic system activation: a randomized trial in healthy subjects.
abstract: ESSENTIALS: In acute coronary syndromes, dual antiplatelet therapy inhibits platelets but confers a bleeding risk. Healthy male volunteers received clopidogrel or ticagrelor plus aspirin or clopidogrel or ticagrelor alone. The decrease in β-thromboglobulin in shed blood was comparable after single and dual antiplatelet therapy. We hypothesize that patients with acute coronary syndromes may not require dual antiplatelet therapy.
  
  
  BACKGROUND
  Dual antiplatelet therapy with a P2Y12 inhibitor and aspirin is standard in acute coronary syndromes. Dual antiplatelet therapy causes more bleeding than single antiplatelet therapy with a P2Y12 inhibitor.
  
  
  OBJECTIVE
  To compare the effects of dual and single antiplatelet therapies on hemostatic system activation.
  
  
  METHODS
  In a randomized, parallel-group, double-blind, placebo-controlled study, 44 healthy volunteers received clopidogrel (600 mg, then 150 mg d(-1) ) and aspirin (100 mg d(-1) ) or placebo for 7 days; An additional 44 volunteers received single-dose ticagrelor (180 mg) and aspirin (300 mg) or placebo. β-Thromboglobulin (β-TG [IU L(-1) ]) and prothrombin fragment 1.2 (f1.2 [nmol L(-1) ]) were measured in blood obtained from bleeding time incisions. Data are given as geometric mean ratio (GMR [95% confidence interval]) to describe the differences in the first 2 h and as mean differences (Δ [95% confidence interval]) in area under the curve (AUC) to discriminate differences in effects over the total observation time.
  
  
  RESULTS
  Clopidogrel plus aspirin and clopidogrel plus placebo reduced β-TG by a GMR of 0.51 (0.42-0.63) and 0.54 (0.46-0.64) at 2 h. Ticagrelor plus aspirin and ticagrelor plus placebo decreased β-TG by a GMR of 0.38 (0.26-0.57) and 0.47 (0.31-0.72). Ticagrelor plus aspirin and ticagrelor plus placebo reduced f1.2 by a GMR of 0.58 (0.45-0.75) and 0.55 (0.38-0.80); clopidogrel did not. Over 24 h, no difference in β-TG occurred between clopidogrel plus aspirin and clopidogrel plus placebo (ΔAUC = -2.9 [-9.9 to 4.1]) or between ticagrelor plus aspirin and ticagrelor plus placebo (ΔAUC = -3.5 [-11.8 to 4.7]). No difference in f1.2 occurred between clopidogrel plus aspirin and clopidogrel plus placebo (ΔAUC = -4.2 [-10.2 to 1.8]) or between ticagrelor plus aspirin and ticagrelor plus placebo (ΔAUC = -3.6 [-10.9 to 3.7]).
  
  
  CONCLUSIONS
  P2Y12 inhibitor monotherapy and dual antiplatelet therapy inhibit hemostatic system activation to a comparable extent.
authors.affiliation: Department of Medicine I, Medical University of Vienna, Vienna, Austria.
authors.forename: L
authors.initials: L
authors.lastname: Traby
authors.affiliation: Department of Medicine I, Medical University of Vienna, Vienna, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Kollars
authors.affiliation: Center for Medical Statistics, Informatics and Intelligent Systems, Medical University of Vienna, Vienna, Austria.
authors.forename: A
authors.initials: A
authors.lastname: Kaider
authors.affiliation: Department of Medicine I, Medical University of Vienna, Vienna, Austria.
authors.forename: S
authors.initials: S
authors.lastname: Eichinger
authors.affiliation: Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Wolzt
authors.affiliation: Department of Medicine I, Medical University of Vienna, Vienna, Austria.
authors.forename: P A
authors.initials: PA
authors.lastname: Kyrle
mesh_terms: D000241:Adenosine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D001241:Aspirin / Q000008:administration & dosage* / Q000009:adverse effects; D001317:Austria; D015415:Biomarkers / Q000097:blood; D001760:Bleeding Time; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D000077144:Clopidogrel; D004311:Double-Blind Method; D064368:Healthy Volunteers; D006487:Hemostasis / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D011237:Predictive Value of Tests; D011516:Prothrombin; D058921:Purinergic P2Y Receptor Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D012372:ROC Curve; D058925:Receptors, Purinergic P2Y12 / Q000187:drug effects* / Q000378:metabolism; D000077486:Ticagrelor; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D013997:Time Factors; D055815:Young Adult; D001620:beta-Thromboglobulin / Q000378:metabolism
chemical_list: D015415:Biomarkers; C548576:P2RY12 protein, human; D010446:Peptide Fragments; D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D058925:Receptors, Purinergic P2Y12; D001620:beta-Thromboglobulin; C045879:prothrombin fragment 1.2; D011516:Prothrombin; D000077144:Clopidogrel; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine; D001241:Aspirin
keywords: acute coronary syndromes; aspirin; clopidogrel; platelet aggregation inhibitors; ticagrelor