Ticagrelor More Rapidly Suppresses Platelet Activity Than Clopidogrel for Low-Risk ACS Patients During Ad Hoc PCI
Ticagrelor results in more potent platelet inhibition compared with clopidogrel in troponin-negative ACS patients undergoing ad hoc PCI, a difference that occurs early after the loading dose and is maintained for at least 8 hours. The late-breaking findings were presented May 7, 2015, at the Society for Cardiovascular Angiography and Interventions Scientific Sessions in San Diego, CA.
The pharmacodynamic study, conducted at 15 US sites, included 100 ACS patients (mean age roughly 62 years; 30% women) who had at least 1 negative troponin test 6 to 48 hours after symptom onset and were undergoing ad hoc PCI.
Researchers led by Roxana Mehran, MD, of Mount Sinai Medical Center (New York, NY), randomized the patients to receive a standard 180-mg loading dose of ticagrelor (Brilinta; AstraZeneca) or a 600-mg loading dose of clopidogrel at the start of PCI. Patients in the ticagrelor group received an additional 90 mg 12 hours after the loading dose, and patients in both groups received a 160- to 500-mg loading dose of aspirin, followed by 75 to 100 mg daily.
Platelet function testing was performed using the VerifyNow assay (Accriva Diagnostics; San Diego, CA) before administration of the loading dose; at the end of PCI; and at 30 minutes, 2 hours, and 8 hours after the loading dose.
Reactivity Lower With Ticagrelor
Mean P2Y12 reactivity unit (PRU) level at 2 hours (primary endpoint) was lower in the ticagrelor group than the clopidogrel group (98.4 vs 257.5; P < .001). A difference was evident as early as at the end of PCI, a mean of 36 minutes after the loading dose.
The percent reduction in PRU level from baseline was greater in ticagrelor-treated than clopidogrel-treated patients at 2 hours (66.3% vs 13.0%) and 8 hours (85.2% vs 32.7%; P < .001 for both). In addition, device-defined inhibition of platelet aggregation favored ticagrelor at every time point after administration of the loading dose.
An exploratory analysis revealed that the percentage of patients with high on-treatment platelet reactivity (PRU ≥ 208) was lower in the ticagrelor group starting at the end of PCI (81.8% vs 97.7%; P = .03). The gap widened at 2 hours (13.3% vs 78.3%) and remained evident at 8 hours (2.4% vs 53.3%; P < .001 for both).
In terms of safety, there were no deaths or drug discontinuations due to adverse events. Rates of individual events were low; with ticagrelor, there were 4 cases of chest pain, 3 of hypotension, and 2 each of dyspnea and hematoma. With clopidogrel, 3 patients developed unstable angina and 1 each had chest pain and dyspnea.
Only 3 adverse events (bleeding) and 1 serious adverse event (duodenitis)—all in the ticagrelor group—were considered drug related.
Ad Hoc PCI Common in Low-Risk ACS Patients
Ticagrelor was approved by the FDA for use in ACS patients in July 2011 based on its reduction of thrombotic events in the PLATO trial. However, nearly all patients in the trial were pretreated with a P2Y12 inhibitor at the point of first clinical contact; thus, very few underwent ad hoc PCI, which accounts for more than half of elective interventions in low-risk ACS patients in the United States, according to Dr. Mehran.
She said at a press briefing that the current findings confirm what was expected in terms of the relative efficacy of ticagrelor compared with clopidogrel for platelet inhibition in this setting.
Dr. Mehran noted that the study was not powered to detect differences in outcomes, so “the clinical implication obviously will need to be tested in a larger population.”
Note: Dr. Mehran is a faculty member of the Cardiovascular Research Foundation, which owns and operates TCTMD.
Mehran R. Ticagrelor versus clopidogrel in troponin-negative patients with acute coronary syndrome undergoing ad-hoc percutaneous coronary intervention: results of a prospective, randomized, multicenter pharmacodynamic study. Presented at: Society for Cardiovascular Angiography and Interventions Scientific Sessions; May 7, 2015; San Diego, CA.
- The study was funded by AstraZeneca.
- Dr. Mehran reports receiving research grants or receiving consulting or advisory board fees from multiple pharmaceutical and other companies.