Original Title: Pharmacodynamic Effects of Switching from Prasugrel to Ticagrelor Results of the Prospective, Randomized SWAP-3 Study
Reference: J Am Coll Cardiol Intv. 2016;() Epub ahead of print.
Courtesy of Dr. Agustín Vecchia.
At present, the pharmacodynamic effects of switching from prasugrel to ticagrelor in patients under dual APT remain unknown. The present prospective, randomized, open study included 82 patients undergoing PCI in the context of ACS.
Patients were divided in three groups: those maintaining prasugrel (10 mg a day), those switching to ticagrelor with loading dose (90 mg every 12 hrs. and a single 180 mg LD) and those switching without loading dose (90 mg every 12 hrs.).
Researchers looked into:
- Platelet reactivity unit levels (PRU) by VerifyNow.
- Platelet reactivity index by vasodilator stimulated phosphoprotein (VASP)
- Platelet aggregation by light transmittance aggregometry (LTA) at 6 time points: baseline, 2 h, 4 h, 24 h, 48 h, and 1 week after randomization.
Lab staff was kept blind to the type of treatment each patient received.
Baseline levels of platelet activity (all under prasugrel) were equal across groups. After switching to ticagrelor, PRU levels decreased 2 hours after administration and this was observed up to 48 hrs. after administration, regardless the use of ticagrelor loading dose.
At one week, PRU levels continued within the safety margin pre-specified by the authors (45 PRU) and reached non inferiority when combining both arms of ticagrelor vs. prasugrel. There was no significant increase of PRU levels (PRU > 208) and, moreover, they remained fairly low during the period studied.
Similar levels of platelet reactivity were observed regardless the use of ticagrelor loading dose. Similar findings were seen when looking at VASP and LTA.
Conclusion
Switching from prasugrel to ticagrelor with or without ticagrelor loading dose in patients that also receive aspirin, produced greater transient platelet inhibition. No interaction between the drugs was observed.
Editorial Comment
Switching between different oral antiplatelets is a relatively frequent practice. It is important to bear in mind that these drugs have different pharmacodynamics and that there is a chance they will interact. Most of the evidence supporting these practices comes from studies on clopidogrel switching, such as the first SWAP trial or the study on healthy people carried out by Payne and collaborators, published in 2008 or, vice versa, on ticagrelor switching to clopidogrel, such as the CAPITAL OPTI-CROSS published at the JACC in March, 2015.
In addition, prior evidence on the same group (SWAP 2 Trial) has shown that switching from ticagrelor to prasugrel produces a transient increase of platelet reactivity, partially mitigated by the use of a loading dose of prasugrel. The present study is one of the few that looks into new generation P2Y12 inhibitor switching and these outcomes have not shown interactions between drugs, even without a loading dose.
It is worth to mention the observed adverse events: 30.9% of patients receiving ticagrelor reported dyspnea (even though mild and in most patients resolved at 24-48 hrs.). Two patients in the ticagrelor group with loading dose were taken off the study for angioedema and one of the patients in the ticagrelor group without loading dose was taken off for dyspnea.
Courtesy of Dr. Agustín Vecchia. German Hospital, Buenos Aires, Argentina.