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J Am Coll Cardiol. 2014 Apr 22;63(15):1500-9. doi: 10.1016/j.jacc.2013.11.032. Epub 2013 Dec 12.

Pharmacodynamic evaluation of switching from ticagrelor to prasugrel in patients with stable coronary artery disease: Results of the SWAP-2 Study (Switching Anti Platelet-2).

Author information

1
Division of Cardiology, University of Florida College of Medicine, Jacksonville, Florida. Electronic address: dominick.angiolillo@jax.ufl.edu.
2
Southampton University Hospital, Southampton, United Kingdom.
3
Sinai Center for Thrombosis Research, Sinai Hospital of Baltimore, Baltimore, Maryland.
4
Medical Affairs, Daiichi Sankyo, Inc., Parsippany, New Jersey.
5
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana.
6
Department of Clinical Pharmacology, Clinic for Cardiology and Angiology II, Universitäts-Herzzentrum Freiburg-Bad Krozingen, Bad Krozingen, Germany.

Abstract

OBJECTIVES:

The goal of this study was to evaluate the pharmacodynamic effects of switching patients from ticagrelor to prasugrel.

BACKGROUND:

Clinicians may need to switch between more potent P2Y12 inhibitors because of adverse effects or switch to the use of a once-daily dosing regimen due to compliance issues.

METHODS:

After a 3- to 5-day run-in phase with a ticagrelor 180-mg loading dose (LD) followed by a ticagrelor 90-mg twice-daily maintenance dose (MD), aspirin-treated patients (N = 110) with stable coronary artery disease were randomized to continue ticagrelor or switch to prasugrel 10-mg once-daily MD, with or without a 60-mg LD. Pharmacodynamic assessments were defined according to P2Y12 reaction unit (PRU) (P2Y12 assay) and platelet reactivity index (vasodilator-stimulated phosphoprotein phosphorylation assay) at baseline (before and after the run-in phase) and 2, 4, 24, and 48 h and 7 days after randomization.

RESULTS:

Platelet reactivity was significantly greater at 24 and 48 h after switching to prasugrel versus continued therapy with ticagrelor, although to a lesser extent in those receiving an LD. Mean PRU remained significantly higher in the combined prasugrel groups versus the ticagrelor group (least-squares mean difference: 46 [95% confidence interval 25 to 67]) and did not meet the primary noninferiority endpoint (upper limit of the confidence interval ≤45), although PRU in the prasugrel cohort was lower at 7 days than at 24 or 48 h. Accordingly, rates of high on-treatment platelet reactivity were higher at 24 and 48 h in both prasugrel groups. At 7 days, there was no difference in high on-treatment platelet reactivity rate between the combined prasugrel and ticagrelor groups.

CONCLUSIONS:

Compared with continued ticagrelor therapy, switching from ticagrelor to prasugrel therapy was associated with an increase in platelet reactivity that was partially mitigated by the administration of an LD.

KEYWORDS:

drug interaction; pharmacodynamics; platelet function; prasugrel; ticagrelor

PMID:
24333493
DOI:
10.1016/j.jacc.2013.11.032
[Indexed for MEDLINE]
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