High On-Treatment Platelet Reactivity Associated With Prasugrel

Objective: To report a case of high on-treatment platelet reactivity (HTPR) with prasugrel maintenance therapy despite adequate initial platelet response to a loading dose. Case Summary: A 51-year-old woman presented to the emergency department complaining of chest pain. She was diagnosed with acute-on-chronic systolic heart failure and non-ST-elevated myocardial infarction (MI). She had a previous MI with bare metal stent placement and was taking aspirin and prasugrel 10 mg daily. Once admitted, a P2Y₁₂ assay revealed HTPR (331 PRU); therefore, prasugrel was reloaded (60 mg). The next day a P2Y₁₂ assay showed adequate platelet reactivity inhibition (118 PRU), so prasugrel 10 mg daily was continued in the hospital and on discharge. Seventeen days after discharge she was readmitted for possible ischemia. On day 3 of admission, a P2Y₁₂ assay revealed HTPR (278 PRU); subsequently, prasugrel was discontinued and ticagrelor started. After 3 doses of ticagrelor, a P2Y₁₂ assay was 97 PRU, so ticagrelor was continued. Five months have passed since discharge. The patient continues to take ticagrelor and has had no further cardiac events. Discussion: HTPR indicates hypo- or nonresponsiveness for antiplatelet agents and may result in serious adverse events. HTPR has rarely been reported with prasugrel or ticagrelor. An objective causality assessment of our case revealed a probable association between HTPR and prasugrel. Conclusion: Patient education and recognition of signs and symptoms associated with prasugrel HTPR may prevent morbidity and mortality from treatment failure. Additional research may determine incidence, risk factors, and optimal management of HTPR with prasugrel.