How Long Does It Take for Clopidogrel and Ticagrelor to Inhibit Platelets in Patients Undergoing Primary Percutaneous Coronary Intervention? A Detailed Pharmacodynamic Analysis: Time Course of Platelet Reactivity in STEMI (TOPS)

Semin Thromb Hemost. 2017 Jun;43(4):439-446. doi: 10.1055/s-0037-1599156. Epub 2017 Apr 4.

Abstract

Antiplatelet therapy plays a pivotal role in patients with an ST-segment elevation myocardial infarction (STEMI) to prevent further atherothrombotic events, such as stent thrombosis. Although the risk of stent thrombosis is highest in the first hours after primary percutaneous coronary intervention (pPCI), little is known about when an adequate level of platelet inhibition is achieved following a clopidogrel or ticagrelor loading dose in STEMI patients. Patients presenting with STEMI in whom pPCI was performed and who were loaded with 600 mg clopidogrel or 180 mg ticagrelor were eligible for enrolment in this nonrandomized, open label, single-center study. Platelet reactivity was measured before PCI, 6 and 24 hours after loading dose and after 2, 7, and 14 days, using the VerifyNow P2Y12 assay as well as 20 µmol/L adenosine diphosphate stimulated light transmittance aggregometry (LTA). We analyzed the time until a VerifyNow result of < 236 P2Y12 reaction units or LTA maximum platelet aggregation of < 64.5% was reached. A total of 28 patients were participated in this study. Platelet reactivity dropped below the high platelet reactivity cutoff level after 11.4 (VerifyNow) and 5.7 (LTA) hours in patients who were loaded with clopidogrel, and after 2.4 (VerifyNow) and 3.9 (LTA) hours in patients who were loaded with ticagrelor. Despite the administration of a clopidogrel or ticagrelor loading dose, it still takes multiple hours (2-11) to reach adequate platelet inhibition in STEMI patients. This might indicate the need for additional antiplatelet therapy in the first hours after loading in patients undergoing pPCI with stenting.

Publication types

  • Clinical Trial

MeSH terms

  • Adenosine / analogs & derivatives*
  • Adenosine / therapeutic use
  • Adult
  • Aged
  • Aged, 80 and over
  • Blood Platelets / drug effects*
  • Clopidogrel
  • Female
  • Humans
  • Male
  • Middle Aged
  • Outcome Assessment, Health Care / methods
  • Outcome Assessment, Health Care / statistics & numerical data
  • Percutaneous Coronary Intervention / methods*
  • Platelet Activation / drug effects
  • Platelet Aggregation Inhibitors / therapeutic use
  • Platelet Function Tests
  • Purinergic P2Y Receptor Antagonists / therapeutic use
  • ST Elevation Myocardial Infarction / blood
  • ST Elevation Myocardial Infarction / surgery*
  • Thrombosis / blood
  • Thrombosis / prevention & control
  • Ticagrelor
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / therapeutic use
  • Time Factors
  • Young Adult

Substances

  • Platelet Aggregation Inhibitors
  • Purinergic P2Y Receptor Antagonists
  • Clopidogrel
  • Ticagrelor
  • Adenosine
  • Ticlopidine