Essential thrombocythemia (ET) is characterized by abnormal megakaryopoiesis and enhanced thrombotic risk. Once-daily (od), low-dose aspirin is the recommended antithrombotic regimen, but accelerated platelet generation may reduce the duration of platelet cyclooxygenase (COX)-1 inhibition. We performed a multicenter, double-blind trial to investigate the efficacy of three aspirin regimens in optimizing platelet COX-1 inhibition while preserving COX-2-dependent vascular thromboresistance. Two-hundred-forty-five patients on chronic od low-dose aspirin were randomized (1:1:1) to receive 100 mg aspirin od, twice-daily, bid), or three-times daily (tid) for 2 weeks. Serum thromboxane B2 (sTXB2), a validated biomarker of platelet COX-1 activity, and urinary prostacyclin metabolite (PGIM) excretion were measured at randomization and after 2 weeks, as primary surrogate endpoints of efficacy and safety, respectively. Urinary TX metabolite (TXM) excretion, gastrointestinal tolerance, and ET-related symptoms were also investigated. Evaluable patients assigned to the bid and tid regimens showed substantially reduced inter-individual variability and lower median values of sTXB2: 19.3[9.7-40], 4 [2.1-6.7], and 2.5[1.4-5.65] ng/ml in the od (n=85), bid (n=79) and tid (n=79) arms, respectively. Urinary PGIM was comparable in the three arms. Urinary TXM was significantly reduced by 35% in both experimental arms. Patients in the tid arm reported a higher abdominal discomfort score. In conclusion, the currently recommended aspirin regimen of 75-100 od for cardiovascular prophylaxis appears largely inadequate in reducing platelet activation in the vast majority of ET patients. The antiplatelet response to low-dose aspirin can be markedly improved by shortening the dosing interval to 12 hours, with no improvement by further reducing it. (EudraCT 2016-002885-30).

Rocca, B., Tosetto, A., Betti, S., Soldati, D., Petrucci, G., Rossi, E., Timillero, A., Cavalca, V., Porro, B., Iurlo, A., Cattaneo, D., Bucelli, C., Dragani, A., Di Ianni, M., Ranalli, P., Palandri, F., Vianelli, N., Beggiato, E., Lanzarone, G., Ruggeri, M., Carli, G., Elli, E. M., Carpenedo, M., Bertozzi, I., Paoli, C., Randi, M. L., Ricco, A., Specchia, G., Vannucchi, A. M., Rodeghiero, F., Patrono, C., De Stefano, V., A randomized, double-blind trial of three aspirin regimens to optimize antiplatelet therapy in essential thrombocythemia, <<BLOOD>>, 2020; (NA): N/A-N/A. [doi:10.1182/blood.2019004596] [http://hdl.handle.net/10807/150626]

A randomized, double-blind trial of three aspirin regimens to optimize antiplatelet therapy in essential thrombocythemia

Rocca, Bianca;Petrucci, Giovanna;Rossi, Elena;Ruggeri, Marco;Patrono, Carlo;De Stefano, Valerio
2020

Abstract

Essential thrombocythemia (ET) is characterized by abnormal megakaryopoiesis and enhanced thrombotic risk. Once-daily (od), low-dose aspirin is the recommended antithrombotic regimen, but accelerated platelet generation may reduce the duration of platelet cyclooxygenase (COX)-1 inhibition. We performed a multicenter, double-blind trial to investigate the efficacy of three aspirin regimens in optimizing platelet COX-1 inhibition while preserving COX-2-dependent vascular thromboresistance. Two-hundred-forty-five patients on chronic od low-dose aspirin were randomized (1:1:1) to receive 100 mg aspirin od, twice-daily, bid), or three-times daily (tid) for 2 weeks. Serum thromboxane B2 (sTXB2), a validated biomarker of platelet COX-1 activity, and urinary prostacyclin metabolite (PGIM) excretion were measured at randomization and after 2 weeks, as primary surrogate endpoints of efficacy and safety, respectively. Urinary TX metabolite (TXM) excretion, gastrointestinal tolerance, and ET-related symptoms were also investigated. Evaluable patients assigned to the bid and tid regimens showed substantially reduced inter-individual variability and lower median values of sTXB2: 19.3[9.7-40], 4 [2.1-6.7], and 2.5[1.4-5.65] ng/ml in the od (n=85), bid (n=79) and tid (n=79) arms, respectively. Urinary PGIM was comparable in the three arms. Urinary TXM was significantly reduced by 35% in both experimental arms. Patients in the tid arm reported a higher abdominal discomfort score. In conclusion, the currently recommended aspirin regimen of 75-100 od for cardiovascular prophylaxis appears largely inadequate in reducing platelet activation in the vast majority of ET patients. The antiplatelet response to low-dose aspirin can be markedly improved by shortening the dosing interval to 12 hours, with no improvement by further reducing it. (EudraCT 2016-002885-30).
2020
Inglese
Rocca, B., Tosetto, A., Betti, S., Soldati, D., Petrucci, G., Rossi, E., Timillero, A., Cavalca, V., Porro, B., Iurlo, A., Cattaneo, D., Bucelli, C., Dragani, A., Di Ianni, M., Ranalli, P., Palandri, F., Vianelli, N., Beggiato, E., Lanzarone, G., Ruggeri, M., Carli, G., Elli, E. M., Carpenedo, M., Bertozzi, I., Paoli, C., Randi, M. L., Ricco, A., Specchia, G., Vannucchi, A. M., Rodeghiero, F., Patrono, C., De Stefano, V., A randomized, double-blind trial of three aspirin regimens to optimize antiplatelet therapy in essential thrombocythemia, <<BLOOD>>, 2020; (NA): N/A-N/A. [doi:10.1182/blood.2019004596] [http://hdl.handle.net/10807/150626]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10807/150626
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