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

Bianca Rocca, Giovanna Petrucci, Elena Rossi, Valerio De Stefano, Marco Ruggeri, Carlo Patrono, Alberto Tosetto, Andrea Timillero, Viviana Cavalca, Benedetta Porro, Alessandra Iurlo, Daniele Cattaneo, Cristina Bucelli, Alfredo Dragani, Mauro Di Ianni, Paola Ranalli, Francesca Palandri, Nicola Vianelli, Eloise Beggiato, Giuseppe LanzaroneGiuseppe Carli, Elena Maria Elli, Monica Carpenedo, Maria Luigia Randi, Irene Bertozzi, Chiara Paoli, Giorgina Specchia, Alessandra Ricco, Alessandro Maria Vannucchi, Francesco Rodeghiero, Ilaria Nichele, Stefania Bellesso, Silvia Artuso, Giovanna Summa, Celeste Santone, Giuseppe Auteri, Stefania Giaquinta, Miriana Arminio, Stefania Priolo, Giulia Bogoni, Paola Guglielmelli, Francesco Mannelli, Giacomo Coltro, Enrica Ravenda, Francesco Albano, Paola Carluccio, Marianna Gentile

Risultato della ricerca: Contributo in rivistaArticolo in rivistapeer review

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).
Lingua originaleEnglish
pagine (da-a)N/A-N/A
RivistaBlood
DOI
Stato di pubblicazionePubblicato - 2020

Keywords

  • essential thrombocythemia

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