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49 (95% CI: 1.44 to 4.32; p = 0.001) and 2.27 (95% CI: 1.57 to 3.03; p < 0.001), respectively. Because peri-procedural MI was included in certain studies, we performed a sensitivity analysis where all events in the first 3 days after PCI were censored. In this 3-day landmark analysis, the results were qualitatively similar to those in the main analysis. The rate of the composite primary endpoint was significantly greater in the high on-treatment platelet reactivity group, 12.7% versus 6.2%, respectively (p < 0.001) (Fig. 4B). The corresponding HR was 1.98 (95% CI: 1.48 to 2.65), for the composite primary endpoint (p < 0.0001). For the components of the primary endpoint, the HR in the landmark Neuronal Signaling analysis was 1.68 (95% CI: 1.04 to 2.71; p = 0.03) for death, 1.86 (95% CI: 1.31 to 2.63; p = 0.0004) for MI, and 2.80 (95% CI: 1.41 to 5.56; p = 0.003) for stent thrombosis. In influence analysis, we investigated the impact of the largest study in the cohort. When the study by Breet et al. (12), which enrolled 1,069 patients, was removed from the analysis, the primary results were unchanged. The HR for the primary endpoint, taking quartile I as referent, was 1.03 (95% CI: 0.59 to 1.82; p = 0.92) for quartile II, 1.75 (95% CI: 1.04 to 2.95; p = 0.035) for quartile III, and 2.15 (95% CI: 1.31 to 3.52; p = 0.003) for quartile IV. For patients with a PRU value ≥230 versus <230, the results were also similar to the main analysis; the HR for death, MI, or stent thrombosis for PRU ≥230 versus <230 was 1.83 (95% CI: 1.27 to 2.62; p = 0.001). We performed a patient-level pooled meta-analysis of 6 prospective studies that quantified on-clopidogrel platelet reactivity with a uniform methodology in patients undergoing PCI. The principal finding of our study is that higher on-treatment platelet reactivity measured using the VerifyNow P2Y12 assay was predictive of long-term ischemic events. We observed a higher event rate of the composite primary endpoint of death, MI, or stent thrombosis for increasing levels of on-treatment platelet reactivity through 2 years of follow-up. Importantly, the highest quartile of PRU values (i.e., highest level of on-treatment platelet reactivity), was also associated with a significant increase in the individual rates of nonfatal MI and stent thrombosis. The event rate for the primary endpoint in the highest quartile of PRU values was significantly greater compared to the lowest quartile, 15.8% versus 5.8% (HR: 2.62; 95% CI: 1.77 to 3.87; p < 0.001). Quartile III was also associated with a higher rate of death, MI, and stent thrombosis when compared to quartile I (p = 0.005). For the primary or secondary endpoints, there were no significant differences between quartiles I and II. Therefore, our observations support a threshold effect for the relationship between on-treatment reactivity and ischemic events after PCI.