CLINICAL STUDIES
Platelet activation in patients after an acute coronary syndrome: results from the TIMI-12 trial
Kenneth A. Ault, MD*,
Christopher P. Cannon, MD ,
Jane Mitchell*,
John McCahan*,
Russell P. Tracy, PhD ,
William F. Novotny, MD ,
James D. Reimann, PhD and
Eugene Braunwald, MD
* Maine Medical Center Research Institute, South Portland, Maine, USA
University of Vermont School of Medicine, Burlington, Vermont, USA
Genentech Inc., South San Francisco, California, USA
Cardiovascular Division, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA
Manuscript received June 29, 1998;
revised manuscript received October 9, 1998,
accepted November 16, 1998.
Reprint requests and correspondence: Dr. Kenneth A. Ault, MMCRI, 125 John Roberts Road, Suite #8, South Portland, Maine 04106
aultk{at}mail.mmc.org
OBJECTIVES
This study was designed to determine the magnitude and time course of platelet activation during therapy of acute coronary syndromes with an oral platelet antagonist.
BACKGROUND
Platelet activation and aggregation are central to the pathogenesis of the acute coronary syndromes (ACS). However, few data are available on levels of platelet activation over time in patients with ACS, especially in the setting of chronic glycoprotein (GP) IIb/IIIa inhibition.
METHODS
The Thrombolysis in Myocardial Infarction (TIMI) 12 trial was a phase II, double-blind trial evaluating the effects of sibrafiban, an oral, selective antagonist of the platelet glycoprotein IIb/IIIa receptor in patients stabilized after an ACS. A subset of 90 of the 329 patients in the study had measurement of platelet activation as assessed by the expression of platelet associated P-Selectin on days 0, 7 and 28. Platelet activation was measured in blood samples that were fixed either immediately (spontaneous activation) or after 5 minute incubation with 0, 1 µM or 5 µM ADP in order to assess platelet responsiveness to very low or moderate stimulation.
RESULTS
At baseline there was a significant elevation of spontaneous platelet activation as compared to samples obtained from normal donors or from patients who did not have acute coronary syndromes (ACS patients 27.6 ± 18.7%, Normal controls 8.5 ± 4.4%, Patient controls 10.9 ± 7.1%, p < 0.005 for both). In addition, there was a significant decrease in the levels of platelet activation with time during the 28 days of treatment with sibrafiban. Nevertheless, even on day 28, the TIMI-12 patients continued to show elevated platelet activation in comparison to the control groups (p < 0.05 for both).
CONCLUSIONS
These results suggest that platelets remain activated long after clinical stabilization post ACS. Although platelet activation decreased after one month of oral GPIIb/IIIa inhibition, levels remained higher than normal, suggesting the need for long-term antiplatelet therapy following ACS.
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Abbreviations and Acronyms
| | ACS | = acute coronary syndromes | | ADP | = adenosine diphosphate | | GP | = glycoprotein | | MI | = myocardial infarction | | PTCA | = percutaneous transluminal coronary angioplasty | | PBS | = phosphate buffered saline | | TIMI | = Thrombolysis in Myocardial Infarction |
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