Abstract 19328: Delayed Ticagrelor Pharmacodynamic Effect in ACS in the Absence of Morphine Therapy and Hemodynamic Compromise
Introduction: The largest body of pharmacodynamic (PD) data on the antiplatelet effect of ticagrelor has been derived from the blood of patients with stable coronary artery disease and the PD effect in stable patients is reported in the package insert for Brilinta. A delayed PD effect of ticagrelor has been reported in acute coronary syndrome (ACS) and has been linked to morphine use and hemodynamic instability.
Methods: We serially compared the pharmacodynamic effect of ticagrelor, assessed by VerifyNow and light transmittance aggregometry (LTA) in patients with ACS (n=15; n=9 NSTEMI; n=6 STEMI) vs. stable coronary artery disease (CAD) (n=54). All ACS patients received a 325 mg aspirin load acutely then 81 mg daily maintenance as compared to 81 mg daily in the stable cohort. All patients were treated with a 180 mg ticagrelor load followed by 90 mg twice daily dose; ACS patients were loaded at the time of percutaneous coronary intervention in the cardiac catheterization laboratory; heparin was used as the anticoagulant; and those with hypotension/shock, prior treatment with morphine or glycoprotein IIb/IIIa inhibitors were excluded.
Results: Patients with ACS exhibited a markedly delayed PD effect by LTA and VerifyNow (Table). PRU was unchanged in the first h in the ACS group (p=NS vs. baseline) and was ~ 3 fold higher at 2 hour vs the stable group (p < 0.0001). As compared to the stable group, where the maximal PD effect occurred within 2 h, a maximal PD effect required > 4 hour in the ACS group.
Conclusions: The PD effect of ticagrelor differs markedly in the settings of ACS and stable CAD in the absence of hypotension and morphine therapy. These findings suggest that factors unrelated to hemodynamics/gut absorption play a role in determining the PD effect of ticagrelor in ACS and may be related to intrinsic differences in platelet physiology in the setting of acute coronary artery thrombosis.
Author Disclosures: K. Bliden: None. U. Tantry: None. D. Emuron: None. R. Chaudhary: None. P. Gurbel: Research Grant; Modest; Coramed, Duke Clinical Research Institute, Haemonetics, Harvard Clinical Research Institute, MedImmune, Merck, NIH, New Haven Pharmaceuticals, Sinnowa. Honoraria; Modest; AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo/Lilly, Haemonetics, Janssen, Merck, New Haven Pharmaceuticals. Ownership Interest; Modest; Merck. Other; Modest; Patent for platelet function testing.
- © 2016 by American Heart Association, Inc.