In low-risk patients with ACS who undergo ad hoc PCI, a loading dose of ticagrelor was associated with greater effects on platelet inhibition and lower high on-treatment platelet reactivity compared with a loading dose of clopidogrel.
Researchers for the prospective, open-label, randomized, parallel-group, phase 4 study evaluated 100 troponin-negative ACS patients undergoing ad hoc PCI at 15 U.S. sites between July 2012 and June 2014. All patients were receiving aspirin therapy but had never received a P2Y12 inhibitor.
Dominick J. Angiolillo
Each participant was randomly assigned a 180-mg loading dose of ticagrelor (Brilinta, AstraZeneca) followed by a 90-mg maintenance dose 12 hours later (n = 51) or a 600-mg loading dose of clopidogrel (n = 49). The VerifyNow assay (Accriva Diagnostics) was used to evaluate platelet reactivity in terms of P2Y12 reaction units (PRU) at five time points: before loading dose, at 0.5, 2 and 8 hours after loading dose, and at the end of PCI.
The primary endpoint was platelet reactivity 2 hours after the ticagrelor or clopidogrel loading dose, quantified as PRU level using the VerifyNow assay.
Patients who received ticagrelor had significantly lower PRU levels at 2 hours after the loading dose compared with those who received clopidogrel (98.4 vs. 257; P < .001); the treatment difference was 159.1 (95% CI, 194.7-123.5). In all randomly assigned patients with PRU measurements available at this time point, similar results were seen. The researchers also reported an overall lower level of platelet reactivity across the study’s time intervals in patients who received ticagrelor vs. clopidogrel (P < .001). PRU level analysis at the different time points demonstrated a nonsignificant decrease in platelet reactivity at 0.5 hours with ticagrelor vs. clopidogrel, with significant differences between the groups emerging at the end-of-PCI assessment (ticagrelor, mean 0.6 ± 0.4 hours from loading dose; clopidogrel, mean 0.6 ± 0.3 hours from loading dose). Significant differences continued up to 8 hours from the loading dose (P < .001), according to the results.
In an exploratory analysis, the researchers found that fewer patients in the ticagrelor group had high on-treatment platelet reactivity at the end of PCI (P = .03), at 2 hours (P < .001) and at 8 hours (P < .001) after loading dose vs. those treated with clopidogrel. Moreover, at 8 hours, 53.3% of patients in the clopidogrel group continued to have high on-treatment platelet reactivity vs. 2.4% of patients in the ticagrelor group.
“These results support that ticagrelor loading dose is more effective than clopidogrel loading dose for inhibition of platelet reactivity in the peri-intervention period in low-risk, troponin-negative ACS patients undergoing ad hoc PCI,” Dominick J. Angiolillo, MD, PhD, director of cardiovascular research and associate professor of medicine at the University of Florida College of Medicine, Jacksonville, and Cardiology Today’s Intervention Editorial Board member, and colleagues concluded.
In a related editorial, Johanne Silvain, MD, PhD, Mathieu Kerneis, MD, and Cardiology Today’s Intervention Editorial Board member Gilles Montalescot, MD, PhD, of the Institut de Cardiologie, Hôpital Pitié-Salpêtrière, Paris, noted that elective PCI is now considered a safe procedure, but it is not without potential complications. These may include PCI-related myonecrosis/myocardial injury or, in rare cases, stent thrombosis, new MI or stroke.
“All of these complications, including postprocedural myonecrosis, have been linked to patient prognosis,” they wrote in the editorial. “There is apparently room for improvement with the use of drugs such as ticagrelor in low-risk or stabilized ACS patients, as well as in stable CAD patients undergoing PCI.” – by Jennifer Byrne
Disclosure: The study was supported by AstraZeneca. Angiolillo reports receiving consultant fees/honorarium from AstraZeneca. Kerneis, Montalescot and Silvain report financial ties with various device and pharmaceutical companies; see the full editorial for a list of the authors’ relevant financial disclosures.