A randomized double-blind trial of 3 aspirin regimens to optimize antiplatelet therapy in essential thrombocythemia

Bianca Rocca, Alberto Tosetto, Silvia Betti, Denise Soldati, Giovanna Petrucci, Elena Rossi, 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 Lanzarone, Marco RuggeriGiuseppe Carli, Elena Maria Elli, Monica Carpenedo, Maria Luigia Randi, Irene Bertozzi, Chiara Paoli, Giorgina Specchia, Alessandra Ricco, Alessandro Maria Vannucchi, Francesco Rodeghiero, Carlo Patrono, Valerio De Stefano

Research output: Contribution to journalArticlepeer-review


Essential thrombocythemia (ET) is characterized by abnormal megakaryopoiesis and enhanced thrombotic risk. Once-daily low-dose aspirin is the recommended antithrombotic regimen, but accelerated platelet generation may reduce the duration of platelet cyclooxygenase-1 (COX-1) inhibition. We performed a multicenter double-blind trial to investigate the efficacy of 3 aspirin regimens in optimizing platelet COX-1 inhibition while preserving COX-2-dependent vascular thromboresistance. Patients on chronic once-daily low-dose aspirin (n = 245) were randomized (1:1:1) to receive 100 mg of aspirin 1, 2, or 3 times daily 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 end points of efficacy and safety, respectively. Urinary TX metabolite (TXM) excretion, gastrointestinal tolerance, and ET-related symptoms were also investigated. Evaluable patients assigned to the twice-daily and thrice-daily regimens showed substantially reduced interindividual variability and lower median (interquartile range) values for sTXB2 (ng/mL) compared with the once-daily arm: 4 (2.1-6.7; n = 79), 2.5 (1.4-5.65, n = 79), and 19.3 (9.7-40; n = 85), respectively. Urinary PGIM was comparable in the 3 arms. Urinary TXM was reduced by 35% in both experimental arms. Patients in the thrice-daily arm reported a higher abdominal discomfort score. In conclusion, the currently recommended aspirin regimen of 75 to 100 once daily for cardiovascular prophylaxis appears to be largely inadequate in reducing platelet activation in the vast majority of patients with ET. The antiplatelet response to low-dose aspirin can be markedly improved by shortening the dosing interval to 12 hours, with no improvement with further reductions (EudraCT 2016-002885-30).

Original languageEnglish
Pages (from-to)171-182
Number of pages12
Issue number2
Publication statusPublished - Jul 9 2020

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology


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