Key result
A double dose of aspirin and clopidogrel significantly increased CEPI closure times compared to standard dose in STEMI patients with high on-treatment platelet reactivity (P<0.001).
Why the study?
Does a double dose of aspirin and clopidogrel improve high on-treatment platelet reactivity in STEMI patients undergoing primary PCI?
RCT (n=116)
Randomized
Does a double dose of aspirin and clopidogrel improve high on-treatment platelet reactivity in STEMI patients undergoing primary PCI?
p-value: p=<0.001
High on-treatment platelet reactivity in STEMI patients is reversible by doubling the dose of aspirin and clopidogrel, and this response can be predicted by baseline VWF and ADAMTS-13 levels.
Double dosing may overcome high on-treatment platelet reactivity in STEMI; extends RCT evidence for intensified antiplatelet regimens in primary PCI.
Von Willebrand factor (VWF) is an emerging risk factor in acute coronary syndromes. Platelet Function Analyzer (PFA-100) with Collagen/Epinephrine (CEPI) is sensitive to functional alterations of VWF and also identifies patients with high on-treatment platelet reactivity (HPR). The objective of this study was to verify the effect of double dose (DD) of aspirin and clopidogrel on HPR detected by PFA-100 and its relation to VWF and to its regulatory metalloprotease ADAMTS-13. Between 2009 and 2011 we enrolled 116 consecutive patients with ST elevation myocardial infarction undergoing primary PCI with HPR at day 5 after PCI. Patients recruited were then randomized between a standard dose (SD, n = 58) or DD of aspirin and clopidogrel (DD, n = 58), maintained for 6 months follow-up. Blood samples for PFA-100, light transmittance aggregometry, and VWF/ADAMTS-13 analysis were collected after 5, 30, and 180 days (Times 0, 1, and 2). At Times 1 and 2 we observed a significantly higher CEPI closure times (CT) in DD as compared to SD (P < 0.001). Delta of CEPI-CT (T1 - T0) was significantly related to VWF (P < 0.001) and inversely related to ADAMTS-13 (0.01). Responders had a significantly higher level of VWF at T0. Finally, in a multivariate model analysis, VWF and ADAMTS-13 in resulted significant predictors of CEPI-CT response (P = 0.02). HRP detected by PFA-100 in acute myocardial infarction is reversible by DD of aspirin and clopidogrel; the response is predicted by basal levels of VWF and ADAMTS-13. PFA-100 may be a useful tool to risk stratification in acute coronary syndromes given its sensitivity to VWF.
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Gianetti et al. (2013) conducted an RCT in ST elevation myocardial infarction (n=116). Double dose of aspirin and clopidogrel vs. Standard dose of aspirin and clopidogrel was evaluated on CEPI closure times (CT) (p=<0.001). A double dose of aspirin and clopidogrel significantly increased CEPI closure times compared to standard dose in STEMI patients with high on-treatment platelet reactivity (P<0.001).
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