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SWAP-3: Switching from prasugrel to ticagrelor can initially increase platelet inhibition
CHICAGO — Patients with ACS who are switched to ticagrelor from prasugrel after PCI initially have higher levels of platelet inhibition in the first few hours with no signs of drug interactions, according to research presented at the American College of Cardiology Scientific Session.
The SWAP-3 study is a prospective, open-label, three-arm parallel-design study that randomized 82 patients on maintenance dual antiplatelet therapy with aspirin 81 mg/day to either continue on a maintenance dose of prasugrel (Effient, Daiichi Sankyo/Eli Lilly) 10 mg daily, or switch to either a dose of ticagrelor 90 mg twice daily (Brilinta, AstraZeneca) with a 180 mg loading dose or ticagrelor without a loading dose.
Francesco Franchi, MD, from the University of Florida College of Medicine–Jacksonville, and colleagues assessed the pharmacodynamic effects within the first week after randomization through three assays: P2Y12 reaction units by VerifyNow (PRU), platelet reactivity index (PRI) by vasodilator-stimulated phosphoprotein and maximal platelet aggregation (MPA) by light transmittance aggregometry.
Three patients were withdrawn from the study because of complications or medication noncompliance, leaving 79 patients in the final analysis (prasugrel, n = 27; ticagrelor with loading dose, n = 25; ticagrelor without loading dose, n = 27).
The primary endpoint of noninferiority of ticagrelor to prasugrel as measured by PRU at 1 week was met, regardless of whether a loading dose was administered, according to the results, which were presented by Gabriel Todd Faz, MD, also from the University of Florida College of Medicine–Jacksonville, and simultaneously published in the JACC: Cardiovascular Interventions.
The PRU levels of the combined ticagrelor groups remained within the 45 PRU noninferiority margin (least squares mean (LSM) difference: –18; 95% CI, –41 to 5). The other two assays produced similar results (LSM difference for PRI: –11; 95% CI, –18 to –4; LSM difference for MPA: –1; 95% CI, –7 to 4).
As early as 2 hours after switching to ticagrelor, decreases in patients’ PRU levels could be observed, and low PRU levels were maintained throughout the follow-up without any drug interaction, according to the researchers. No increases in high platelet reactivity (PRU > 208) were observed.
The researchers acknowledged that bleeding is a concern with low platelet reactivity, but they wrote that “significant reductions in platelet reactivity were limited to the first 48 [hours] after switching” and that they did not “observe any major bleeding complications.”
“Overall, these results provide important [pharmacodynamic] insights to clinicians who may choose to switch patients from prasugrel to ticagrelor therapy, which can be performed without any concerns for drug interactions by simply transitioning to a standard 90 mg [twice daily] dosing regimen, without the need for a [loading dose],” the researchers wrote. – by Tracey Romero
Reference:
Faz GT, et al. Abstract 1174-131. Presented at: American College of Cardiology Scientific Session; April 2-4, 2016; Chicago.
Franchi F, et al. J Am Coll Cardiol Intv. 2016; doi:10.1016/j.jcin.2016.02.039.
Disclosure: The study was funded by AstraZeneca. Franchi and Faz report no relevant financial disclosures. Please see full study for list of all other authors’ relevant financial disclosures.