Discussion

BACKGROUND: High residual platelet reactivity (HRPR) in NSTEMI patients on clopidogrel is common and associated with adverse ischaemic outcomes. Despite this, near-patient platelet function testing and tailored pharmacotherapy has failed to show benefit. We therefore examined the large variations of peri-procedural platelet function that occur in NSTEMI patients without changes to pharmacotherapy
METHODS: 45 NSTEMI patients treated with PCI were studied after receiving 600mg loading dose of clopidogrel followed by a mean 4.2 days of 75mg clopidogrel. Samples were taken immediately before PCI (PrePCI), Immediately after (PostPCI) and at 24 hours (24hrPCI). There were no changes to oral or addition of IV antiplatelet agents. Platelet function measured using Multiplate (MP) system with ADP & TRAP. Serum quantification of soluble p-selectin using ELISA and whole blood flow cytometry to quantify numbers p-selectin positive platelets.
RESULTS: PrePCI 48.5% of patients had HRPR by MP(>469 Aggregation units AU to 5 µM ADP). Mean values PrePCI 471.4 AU (SEM41.5), PostPCI 395.9 AU (SEM35.2) and 24hrPCI 265.9 AU (SEM24). A highly significant reduction prePCI to 24hrPCI 205.5 AU (p=<0.0001) was seen resulting in only 2 patients or 4.4% had HRPR at 24hrs. Soluble p-selectin showed the opposite trend, pre-PCI concentrations of 30.6ng (SEM 2.2), PostPCI 30.55 ng (SEM2.4) and 24 hr post PCI 37.5ng (SEM 2.8). Percentage of total platelets expressing p-selectin showed persistent activation, PrePCI 2.9%, PostPCI 4.6% and 24hrPCI 5.4%
CONCLUSION: Near-patient platelet function testing (MP) indicates a considerable improvement in platelet inhibition over the 24 hours following PCI with the majority of patients having full P2Y12 inhibition at 24 hours despite no change in pharmacotherapy. However, soluble and platelet bound p-selectin measures suggest this “improved” inhibition may be misleading with on-going platelet activation and loss of platelet function rather than increased inhibition. These results suggest timing is crucial when interpreting platelet function test results and may shed light on some of the limitations of recent tailored therapy trials.