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Abstract
Introduction Oral anti-platelet agents are a cornerstone of treatment for acute coronary syndromes (ACS), and improve outcome after percutaneous coronary intervention (PCI). Low responses to aspirin (ASA) and Clopidogrel place patients at higher risk of subsequent adverse cardiac and cerebrovascular events (ACCE). Near-patient testing devices and markers of platelet activation may identify this risk, but strategies for their use have yet to be developed.
Methods Two hundred and sixty nine consecutive patients (68.4% male, 18.6% diabetic) with ACS were studied prospectively. All patients displayed high risk features (elevated serum troponin (Tn), ECG abnormalities or both), received standard therapy and were due to undergo early angiography with a view to PCI. Those with other factors likely to influence platelet function testing were excluded. At angiography, blood was drawn for platelet count and TnT; response to ASA and to clopidogrel using a VerifyNow (VN) near patient testing device; plasma P-selectin levels; and presence of the CYP2 C19 2* allele, GPIIIa PlA1/2 and ABCB1 polymorphisms. Procedural outcomes were recorded and TnT repeated 16—24 h after PCI. At a 30-day visit clinical data were recorded and blood tests repeated. Patients were followed-up for ACCE (death, MI, repeat revascularisation, stroke and unplanned cardiovascular admission) at 30 days, 6 and 12 months.
Results VN results were available for 267 patients. For Clopidogrel, P2Y12 reaction units (PRU)>240 and ASA reaction units (ARU) ≥550 indicate a low response to each agent. PRU of >240 was observed in 46.2% of patients, associated with increasing age (p=0.003) diabetes (p=0.027), platelet count (p=0.001) and CYP2 C19 2* status (p<0.001), but not GPIIIa PlA or ABCB1 status. Low response to Clopidogrel at presentation did not predict ACCE at 12 months. Only 6(2.3%) had an ARU≥550, patients with an adverse event at 12 months displaying higher ARU readings at presentation (450.3±53.3 vs 428.9±46.1, p=0.023).
151 (56.1%) underwent PCI, of whom 73(48.7%) demonstrated low response to Clopidogrel at presentation. This was associated with a greater periprocedural rise in Tn (p=0.046) and higher 30 day P-selectin (p=0.014), but did not predict ACCE at 12 months. CYP2 C19 2* status predicted VN PRU at angiography (p=0.001) and 30 days (p=0.022), but not ACCE. Low response to ASA at angiography was also associated with higher plasma P-selectin levels at 30 days (p=0.001), but did not predict ACCE at 12 months. Clopidogrel response at 30 days did predict 12 month ACCE (p=0.017), although P-selectin levels at 30 days were strongly associated (p=0.005).
Conclusions Near-patient testing for clopidogrel response identified patients at risk of subsequent events when performed 30 days following PCI, but not at presentation. P-selectin, a marker of residual platelet activation, was associated with low response to each agent when measured at 30 days, and may alone be a better indicator of increased risk.
Event free survial and verify now P2Y12 reactivity units (PRU) measured at 30 days
Event free survival and verify now P2Y12 reactivity units (PRU) measured at 30 days. (p=0.017).
- Antiplatelet agents
- near patient testing
- P-selectin