title: A randomised study for optimising crossover from ticagrelor to clopidogrel in patients with acute coronary syndrome. The CAPITAL OPTI-CROSS Study.
abstract: Ticagrelor has been endorsed by guidelines as the P2Y12inhibitor of choice in patients with acute coronary syndrome. Clinically, some patients on ticagrelor will require a switch to clopidogrel; however, the optimal strategy and pharmacodynamics effects of switching remain unknown. Patients with an indication to switch were randomly assigned to either a bolus arm (Clopidogrel 600 mg bolus followed by 75 mg daily, n=30) or a no-bolus arm (Clopidogrel 75 mg daily, n=30). Blood samples were collected at baseline, 12, 24, 48, 54, 60 and 72 hours (h) for assessment of platelet reactivity. The primary outcome was P2Y12reactivity units (PRU) at 72 h. Secondary outcomes included: PRUs at each time point, incidence of high on-treatment platelet reactivity (HPR), major adverse cardiac events (MACE) and TIMI bleeding at 30 days. Serial PRUs increased after switching to clopidogrel in both groups. At 72 h, no difference in PRU was observed (165.8 ± 71.0 vs 184.1 ± 67.7, bolus vs no bolus, respectively, p=0.19). At 48 h the PRUs were significantly lower in the bolus arm (114 ± 73.1 vs 165.1 ± 70.5, respectively; p=0.0076) and at 72 h, there was a significant reduction in incidence of HPR (26.7 % vs 56.7 %, p=0.02). No differences in MACE or TIMI bleeding were observed. Although a bolus strategy was not associated with improved platelet inhibition at 72 h; at 48 h, platelet inhibition was superior with reduced incidence of HPR. Larger studies will be required to determine its clinical significance. Until then, decision for giving a bolus of clopidogrel at the time of a switch may in part be dependent on the indication for switching, especially if there are concerns for bleeding risk.
authors.forename: Ali
authors.initials: A
authors.lastname: Pourdjabbar
authors.forename: Benjamin
authors.initials: B
authors.lastname: Hibbert
authors.forename: Aun-Yeong
authors.initials: AY
authors.lastname: Chong
authors.forename: Michel R
authors.initials: MR
authors.lastname: Le May
authors.forename: Marino
authors.initials: M
authors.lastname: Labinaz
authors.forename: Trevor
authors.initials: T
authors.lastname: Simard
authors.forename: F Daniel
authors.initials: FD
authors.lastname: Ramirez
authors.forename: Peter
authors.initials: P
authors.lastname: Lugomirski
authors.forename: Ronnen
authors.initials: R
authors.lastname: Maze
authors.forename: Michael
authors.initials: M
authors.lastname: Froeschl
authors.forename: Christopher
authors.initials: C
authors.lastname: Glover
authors.forename: Alexander
authors.initials: A
authors.lastname: Dick
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Marquis
authors.forename: Jordan
authors.initials: J
authors.lastname: Bernick
authors.forename: George
authors.initials: G
authors.lastname: Wells
authors.affiliation: Derek Y. F. So MD, University of Ottawa Heart Institute, 40 Ruskin Street, Room H3408, Ottawa, Ontario K1Y 4W7, Canada, Tel.: +1 613 761 5387, Fax: +1 613 761 4338, E-mail: dso@ottawaheart.ca.
authors.forename: Derek Y F
authors.initials: DY
authors.lastname: So
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D000241:Adenosine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000368:Aged; D000369:Aged, 80 and over; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D000077144:Clopidogrel; D018592:Cross-Over Studies; D004334:Drug Administration Schedule; D057915:Drug Substitution; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D009864:Ontario; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D010979:Platelet Function Tests; D011446:Prospective Studies; D058921:Purinergic P2Y Receptor Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D058925:Receptors, Purinergic P2Y12 / Q000097:blood / Q000187:drug effects; D012307:Risk Factors; D000077486:Ticagrelor; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D058925:Receptors, Purinergic P2Y12; D000077144:Clopidogrel; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine
keywords: Pharmacodynamics; acute coronary syndrome; clopidogrel; platelet function; ticagrelor