Author + information
- Received November 16, 2009
- Revision received February 5, 2010
- Accepted February 9, 2010
- Published online September 21, 2010.
- Dominick J. Angiolillo, MD, PhD⁎,⁎ (, )
- Jorge F. Saucedo, MD†,
- Roger DeRaad, MN‡,
- Andrew L. Frelinger, PhD§∥,
- Paul A. Gurbel, MD¶,
- Timothy M. Costigan, PhD#,
- Joseph A. Jakubowski, PhD#,
- Clement K. Ojeh, PhD#,
- Mark B. Effron, MD#,
- SWAP Investigators
- ↵⁎Reprint requests and correspondence:
Dr. Dominick J. Angiolillo, Cardiology Research, University of Florida Jacksonville, 655 West 8th Street, ACC 5th Floor, Jacksonville, Florida 32209
Objectives The objective was to evaluate the pharmacodynamic response of switching patients on maintenance phase clopidogrel therapy after an acute coronary syndrome (ACS) to prasugrel.
Background Prasugrel P2Y12 receptor blockade is associated with greater pharmacodynamic platelet inhibition and reduction of ischemic complications compared with that of clopidogrel in ACS patients undergoing percutaneous coronary intervention. The pharmacodynamic effects of switching patients during maintenance phase clopidogrel therapy after an ACS event to prasugrel are unknown.
Methods The SWAP (SWitching Anti Platelet) study was a phase 2, multicenter, randomized, double-blind, double-dummy, active-control trial. After a run-in of daily open-label clopidogrel 75 mg with aspirin therapy for 10 to 14 days, patients were randomly assigned to 1 of the following 3 treatments: placebo loading dose (LD)/clopidogrel 75 mg maintenance dose (MD), placebo LD/prasugrel 10 mg MD, or prasugrel 60 mg LD/10 mg MD. Platelet function was evaluated at 2 h, 24 h, 7 days, and 14 days using light transmittance aggregometry, VerifyNow P2Y12 assay, and vasodilator-stimulated phosphoprotein phosphorylation.
Results A total of 139 patients were randomized, of whom 100 were eligible for analysis. Maximum adenosine diphosphate-induced platelet aggregation (20 μM) by light transmittance aggregometry at 1 week (primary end point) was lower after prasugrel MD compared with clopidogrel MD (41.1% vs. 55.0%, p < 0.0001), and was also lower in the prasugrel LD+MD group compared with clopidogrel MD (41.0% vs. 55.0%, p < 0.0001). At 2 h, a prasugrel LD resulted in higher platelet inhibition compared with the other regimens. Similar results were found using light transmittance aggregometry with 5 μM adenosine diphosphate, VerifyNow P2Y12, and vasodilator-stimulated phosphoprotein phosphorylation assays.
Conclusions For patients receiving maintenance clopidogrel therapy after an ACS event, switching from clopidogrel to prasugrel is associated with a further reduction in platelet function by 1 week using prasugrel MD or within 2 h with the administration of a prasugrel LD. (A Pharmacodynamic Comparison of Prasugrel [LY640315] Versus Clopidogrel in Subjects With Acute Coronary Syndrome Who Are Receiving Clopidogrel [SWAP]; NCT00356135)
The investigators and the centers participating in the SWAP study are listed in the Online Appendix. Financial support was provided by Daiichi Sankyo Inc. and by Eli Lilly and Company. Dr. Angiolillo reports receiving honoraria for lectures from Bristol-Myers Squibb, Sanofi-Aventis, Eli Lilly, and Daiichi Sankyo; consulting fees from Bristol-Myers Squibb, Sanofi-Aventis, Eli Lilly, Daiichi Sankyo, The Medicines Company, Portola, Novartis, Medicure, Accumetrics, Arena Pharmaceuticals, and AstraZeneca; and research grants from GlaxoSmithKline, Otsuka, Eli Lilly, Daiichi Sankyo, The Medicines Company, Portola, Accumetrics, Schering-Plough, AstraZeneca, Eisai, and Johnson & Johnson. Dr. Saucedo reports grant and research support from The Medicines Company, AstraZeneca, Abbott Vascular, Bristol-Myers Squibb, Medtronic, and Eli Lilly; and grant support, consulting fees, and honoraria from Schering-Plough. Dr. Frelinger reports grant and research support from Bristol-Myers Squibb, Sanofi-Aventis, Eli Lilly, Daiichi Sankyo, and GLSynthesis; and consulting fees from Eli Lilly. Dr. Gurbel reports receiving honoraria for lectures from Sanofi-Aventis, AstraZeneca, Eli Lilly, Daiichi Sankyo, and Schering-Plough; consulting fees from Schering-Plough, AstraZeneca, Portola, Haemoscope, Sanofi, Pozen, and Bayer; and grant and research support from Schering-Plough, AstraZeneca, Portola, Haemoscope, and Bayer. Drs. Costigan, Jakubowski, Ojeh, and Effron are employees of and report equity ownership of or stock options in Eli Lilly. All other authors have reported that they have no relationships to disclose.
- Received November 16, 2009.
- Revision received February 5, 2010.
- Accepted February 9, 2010.
- American College of Cardiology Foundation