title: Relationship between peripheral arterial reactive hyperemia and residual platelet reactivity after 600 mg clopidogrel.
abstract: Clopidogrel reduces long-term ischemic events in patients with acute coronary syndrome or stable angina (SA) undergoing percutaneous coronary intervention (PCI). Endothelial function improvement has been proposed, among other factors, for this beneficial effect of clopidogrel, but whether this might be associated to its anti-platelet action remains unclear. We tested the hypothesis that clopidogrel improvement of peripheral vascular endothelial function might be associated with inhibition of platelet aggregation. Endothelial function was evaluated before and at least 12 h after 600 mg clopidogrel in 43 SA pts undergoing elective PCI by: (a) reactive hyperemia peripheral arterial tonometry (measuring the Endoscore); (b) circulating endothelial microparticles (EMPs). Response to clopidogrel was measured with point-of-care VerifyNow P2Y12 assay and expressed as platelet reaction unit (PRU) and percent platelet inhibition (%PI). High platelet reactivity after clopidogrel was defined as PRU ≥ 240. Endothelial function improved after clopidogrel in 20 pts. Changes in Endoscore (Δ Endoscore) were significantly correlated with both PRU (r = -0.61, P < 0.001) and %PI (r = 0.57, P < 0.001). Endoscore significantly increased after clopidogrel in pts with PRU < 240 (0.38 ± 0.26 to 0.57 ± 0.33, P < 0.001), but did not in pts with PRU ≥ 240 (0.53 ± 0.31 to 0.40 ± 0.37, P = 0.12). EMPs were also significantly reduced in pts with PRU < 240 (222 [140-593] to 142 [83-371]/μl, P = 0.001), while no changes were observed in pts with PRU ≥ 240 (256 [178-531] to 388 [238-499]/μl, P = 0.55). In patients with stable coronary artery disease, a single 600 mg clopidogrel loading dose improves vascular endothelial function. This improvement is associated with optimal platelet inhibition and it is not observed in patients with post-clopidogrel high platelet reactivity.
authors.affiliation: Cardiovascular Center Aalst, OLV Hospital, Moorselbaan 164, 9300, Aalst, Belgium.
authors.forename: Michalis
authors.initials: M
authors.lastname: Hamilos
authors.forename: Olivier
authors.initials: O
authors.lastname: Muller
authors.forename: Argyrios
authors.initials: A
authors.lastname: Ntalianis
authors.forename: Catalina
authors.initials: C
authors.lastname: Trana
authors.forename: Jozef
authors.initials: J
authors.lastname: Bartunek
authors.forename: Giovanna
authors.initials: G
authors.lastname: Sarno
authors.forename: Fabio
authors.initials: F
authors.lastname: Mangiacapra
authors.forename: Karen
authors.initials: K
authors.lastname: Dierickx
authors.forename: Peter
authors.initials: P
authors.lastname: Meeus
authors.forename: Thomas
authors.initials: T
authors.lastname: Cuisset
authors.forename: Bernard
authors.initials: B
authors.lastname: De Bruyne
authors.forename: William
authors.initials: W
authors.lastname: Wijns
authors.forename: Emanuele
authors.initials: E
authors.lastname: Barbato
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood / Q000188:drug therapy; D000368:Aged; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000097:blood / Q000188:drug therapy; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D006801:Humans; D006940:Hyperemia / Q000097:blood* / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged; D015539:Platelet Activation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D010979:Platelet Function Tests; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D013997:Time Factors
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine