Administration of a Loading Dose Has No Additive Effect on Platelet Aggregation During the Switch From Ongoing Clopidogrel Treatment to Ticagrelor in Patients With Acute Coronary Syndrome

Abstract

Background— Ticagrelor outperforms clopidogrel in preventing cardiovascular events in acute coronary syndrome. Despite the inclusion of a loading dose in the Platelet Inhibition and Patient Outcomes (PLATO) trial for all patients randomized to ticagrelor, it may not be necessary in patients receiving ongoing clopidogrel therapy. The aim of the present study was to assess whether a ticagrelor loading dose is associated with a further platelet inhibition during the switch from clopidogrel to ticagrelor in patients with acute coronary syndrome receiving ongoing antiplatelet treatment. Methods and Results— Fifty patients with acute coronary syndrome receiving aspirin and clopidogrel treatment were randomly assigned to a starting dose of ticagrelor (group 1, 90 mg; group 2, 180 mg). Platelet aggregation was measured using multiple electrode aggregometry and standard light transmission aggregometry just before the switch and at 2, 6, 24, and 72 hours. No relevant difference in platelet aggregation was observed between the 2 study arms at baseline ( P =0.256). Residual platelet aggregation was significantly reduced in both arms 2 hours after the first administration of ticagrelor ( P <0.001 for both), with no difference in aggregation between groups (multiple electrode aggregometry, 17.6±7.2 versus 18.1±6 U; P =0.281). Similar results were observed with LTA. Conclusions— Switching from clopidogrel to ticagrelor without a reloading dose is feasible, and it does not hinder platelet aggregation inhibition in patients with acute coronary syndrome. Further prospective studies are needed to assess the clinical relevance of our findings. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01795820.

Effect of a 180 mg ticagrelor loading dose on myocardial necrosis in patients undergoing elective percutaneous coronary intervention: A preliminary study

“…Platelet aggregation is also significantly reduced 2 h after the first administration of ticagrelor [10]. So hs-cTnT was chosen at 2 h after PCI as a parameter to reflect whether a loading dose of ticagrelor could decrease post-PCI myocardial necrosis in stable CAD patients already receiving clopidogrel therapy.…”

“…In the PLATelet inhibition and patient Outcomes (PLATO) trial, reversible long-term P2Y12 inhibition with ticagrelor was better than that with clopidogrel for the prevention of cardiovascular and total death, myocardial infarction (MI), and stent thrombosis, without an increase in the rates of major bleeding in a broad population of patients with ACS, who began treatment upon hospital admission [7,8]. Although a loading dose of ticagrelor was used in PLATO trial [9], a recent study demonstrated that a loading dose of ticagrelor was not associated with a further platelet inhibition after switching from clopidogrel to ticagrelor for patients with ACS receiving ongoing clopidogrel treatment [10]. However, the above study only included clopidogrel responders [10].…”

“…Although a loading dose of ticagrelor was used in PLATO trial [9], a recent study demonstrated that a loading dose of ticagrelor was not associated with a further platelet inhibition after switching from clopidogrel to ticagrelor for patients with ACS receiving ongoing clopidogrel treatment [10]. However, the above study only included clopidogrel responders [10]. It is known that a large number of patients with coronary artery disease (CAD) have diabetes and patients with diabetes had a higher number of clopidogrel non-responders, and increased platelet reactivity compared with nondiabetic subjects on combined aspirin and clopidogrel treatment [11].…”

International Expert Consensus on Switching Platelet P2Y 12 Receptor–Inhibiting Therapies

“…49 Many other studies exploring the pharmacodynamic profiles of switching from clopidogrel to prasugrel or ticagrelor have been conducted (Tables II and III in the online-only Data Supplement). 18,[48][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65][66] All studies have consistently shown enhanced platelet inhibition when escalating from clopidogrel to prasugrel or ticagrelor, regardless of clinical setting, as well as a reduction in rates of high on-treatment platelet reactivity (HPR), 18,48-70 a well-defined marker of risk of ischemic recurrences, including stent thrombosis. 10,11 These effects are achieved more promptly after administration of an LD compared with an MD regimen.…”

Response to Letter Regarding, “Administration of a Loading Dose Has No Additive Effect on Platelet Aggregation During the Switch From Ongoing Clopidogrel Treatment to Ticagrelor in Patients With Acute Coronary Syndrome”

“…2 The novel antiplatelet agent, ticagrelor, has several advantages over the long-standing clopidogrel, as the virtual absence of nonresponders and the more powerful platelet inhibition. As highlighted by Gurbel et al, 1 clopidogrel nonresponders were excluded from our study, for multiple reasons.…”