i[VREY]₄ improves the inhibitory effect of standard antiplatelet therapy without increasing the risk of bleeding. (A) The effect of aspirin (300 µg/mL), cangrelor (0.34 µg/mL), and i[VREY]₄ (5 µM) alone or in combination on collagen/epinephrine closure time was measured with the platelet function analyzer-200 device (n = 5). (B-G) Platelet aggregation was assessed by MEA in human blood activated with collagen (0.1 µg/mL) and recombinant CXCL12 (0.1 µg/mL), CXCL12 alone (1 µg/mL), or human plaque homogenate (833 µg/mL). The blood was pretreated for 1 hour either with dimethyl sulfoxide as a control, aspirin (300 µg/mL) alone, or in combination with i[VREY]₄ (5 µM) or cangrelor (0.34 µg/mL) alone or in combination with i[VREY]₄ (n = 8). Data represent mean ± standard deviation from the indicated numbers of independent experiments. *P ≤ .05, **P ≤ .01, ***P ≤ .001, ****P ≤ .0001 as analyzed by repeated measure one-way analysis of variance with Tukey’s multiple comparison test. AU, arbitrary units; ns, not significant.