Author + information
- Received July 29, 2010
- Revision received October 11, 2010
- Accepted October 12, 2010
- Published online February 8, 2011.
- Claes Held, MD, PhD⁎,⁎ (, )
- Nils Åsenblad, MSc, PhLic⁎,
- Jean Pierre Bassand, MD†,
- Richard C. Becker, MD‡,
- Christopher P. Cannon, MD§,
- Marc J. Claeys, MD, PhD∥,
- Robert A. Harrington, MD‡,
- Jay Horrow, MD¶,
- Steen Husted, MD, DSc#,
- Stefan K. James, MD, PhD⁎,
- Kenneth W. Mahaffey, MD‡,
- José C. Nicolau, MD, PhD⁎⁎,
- Benjamin M. Scirica, MD, MPH§,
- Robert F. Storey, MD, DM††,
- Marius Vintila, MD, PhD‡‡,
- Joseph Ycas, PhD¶ and
- Lars Wallentin, MD, PhD⁎
- ↵⁎Reprint requests and correspondence:
Dr. Claes Held, Uppsala Clinical Research Center and Department of Medical Sciences, Uppsala University, Department of Cardiology, Dag Hammarskjölds v 14B, Uppsala 75185, Sweden
Objectives The purpose of this study is to evaluate the efficacy and safety of ticagrelor and clopidogrel in patients with acute coronary syndrome undergoing coronary artery bypass graft surgery (CABG), as a post-randomization strategy.
Background Ticagrelor is a novel, reversibly binding, oral, direct-acting P2Y12-receptor antagonist. In the PLATO (Platelet Inhibition and Patient Outcomes) trial, which randomized 18,624 patients with acute coronary syndromes, ticagrelor compared with clopidogrel significantly reduced the risk of the primary composite end point of cardiovascular (CV) death, myocardial infarction, or stroke (hazard ratio [HR]: 0.84; 95% confidence interval [CI]: 0.77 to 0.92; p < 0.001). This report investigated the outcomes of patients treated with CABG during the trial.
Methods In total, 1,899 patients underwent CABG post-randomization. The protocol recommended ticagrelor/placebo to be withheld for 24 to 72 h and clopidogrel/placebo for 5 days preoperatively. In all, 1,261 patients underwent CABG and were receiving study drug treatment <7 days before surgery. The statistical analysis was based on events occurring from the CABG procedure until the end of the study, excluding 3 patients with CABG after study end.
Results In the 1,261 patient cohort, the relative reduction of primary composite end point at 12 months (10.6% [66 of 629] with ticagrelor versus 13.1% [79 of 629] with clopidogrel; HR: 0.84; 95% CI: 0.60 to 1.16; p = 0.29) was consistent with the results of the whole trial. Total mortality was reduced from 9.7% (58 of 629) to 4.7% (29 of 629; HR: 0.49; 95% CI: 0.32 to 0.77; p < 0.01), CV death from 7.9% (47 of 629) to 4.1% (25 of 629; HR: 0.52; 95% CI: 0.32 to 0.85; p < 0.01), and non-CV death numerically from 2.0% to 0.7% (p = 0.07). There was no significant difference in CABG-related major bleeding between the randomized treatments.
Conclusions In the subgroup of patients undergoing CABG within 7 days after the last study drug intake, ticagrelor compared with clopidogrel was associated with a substantial reduction in total and CV mortality without excess risk of CABG-related bleeding.
The PLATO study was funded by AstraZeneca. For full author disclosures, please see the end of this article.
- Received July 29, 2010.
- Revision received October 11, 2010.
- Accepted October 12, 2010.
- American College of Cardiology Foundation