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Ticagrelor does not impact cellular adenosine uptake in stable CAD
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A study published in Circulation showed that two different dose regimens of ticagrelor maintenance therapy had no effect on cellular adenosine uptake at 1 month in stable patients with CAD.
The results of the STEEL-PCI study also showed that there was no effect on systemic plasma adenosine levels, researchers reported.
“In the absence of contraindications or concurrent oral anticoagulant therapy, ticagrelor is recommended in preference to clopidogrel for patients with acute coronary syndromes, including those managed with PCI, but has not been assessed in patients undergoing PCI for stable CAD,” Rachel C. Orme, MD, from the department of infection, immunity and cardiovascular disease at the University of Sheffield, U.K., and colleagues wrote in the study background. “Similarly, prasugrel is recommended in preference to clopidogrel for ACS patients managed with PCI but is not licensed for use in stable CAD. Consequently, aspirin and clopidogrel remain the predominant DAPT strategy in stable CAD patients undergoing PCI.”
To compare the pharmacodynamic effects of ticagrelor (Brilinta, AstraZeneca) and clopidogrel in a stable population, Orme and colleagues randomly assigned 180 aspirin-treated patients with stable CAD planned to undergo elective PCI in a single center to a standard clopidogrel regimen or one of two regimens of ticagrelor, either 90 mg (T90) or 60 mg twice daily (T60), both with a 180-mg loading dose.
The researchers assessed cellular adenosine uptake at the time of the procedure and pre- and postdose at 1 month.
At the same time, Orme and colleagues assessed systemic plasma adenosine concentration and platelet reactivity.
High-sensitivity troponin T (hsTnT) was measured before and 18 to 24 hours after PCI.
One hundred seventy-four patients underwent an invasive procedure, 162 of whom received PCI.
According to the study, there was no observed effect postdose at 1 month for either ticagrelor dose compared with clopidogrel on in vitro adenosine uptake (residual adenosine at 15 seconds, mean ± standard deviation [SD]: clopidogrel, 0.274 ± 0.101 mol/L; T90, 0.278 ± 0.134 mol/L; T60, 0.288 ± 0.149 mol/L; P = .37).
No effect of ticagrelor on in vitro adenosine uptake was seen at other time points, nor was plasma adenosine concentration affected (P > .1 for all), the researchers wrote.
The study showed that compared with clopidogrel, both maintenance doses of ticagrelor achieved more potent and consistent platelet inhibition (VerifyNow P2Y12 reaction units [PRU], 1 month, mean ± SD: predose, T60: 62 ± 47; T90: 40 ± 38; clopidogrel 181 ± 44; postdose, T60: 34 ± 30; T90: 24 ± 21; clopidogrel 159 ± 57; P < .0001 for ticagrelor vs clopidogrel).
The rate of high platelet reactivity was significantly less with both T60 and T90 compared with clopidogrel (VerifyNow PRU > 208, 1-month postdose: 0%, 0% and 21%, respectively), according to the data.
The researchers found a median hsTnT increase of 16.9 ng/L (interquartile range [IQR], 6.5-46.9) for clopidogrel, 22.4 ng/L (IQR, 5.5-53.8) for T60 and 17.7 ng/L (IQR, 8.1-43.5) for T90 (P = .95), and also that there was a trend toward less dyspnea with T60 vs. T90 (7.1% vs 19%; P = .09).
“Contrary to some previous published studies, we found no evidence of any effect of the ticagrelor regimens on cellular adenosine uptake or plasma adenosine concentration. The reasons for this are unclear since our data show clearly that the assay assessed adenosine uptake over 1 minute in whole-blood samples, with the expected baseline levels of adenosine after in vitro addition of 1 mol/L (indicating efficacy of the stop solution in preventing further adenosine uptake) and almost complete adenosine uptake at 1 minute (indicating efficacy of the stop solution in preventing adenosine generation),” Orme and colleagues wrote. “Further work is warranted to characterize the efficacy and safety of ticagrelor in this clinical setting.” – by Dave Quaile
Disclosures: The study was funded by an investigator-initiated grant from AstraZeneca. Orme reports no relevant financial disclosures. One author reports receiving institutional research grants and support from AstraZeneca and PlaqueTec, consultant fees from AstraZeneca, Actelion, Avacta, Bayer, Bristol-Myers Squibb/Pfizer, Idorsia, Novartis, PlaqueTec and The Medicines Company and speaker fees from AstraZeneca.