Results of a phase II trial showed twice daily dosing of low-dose aspirin was optimal in the setting of essential thrombocythemia (ET). These finding were reported in Blood.
ET, a Philadelphia chromosome-negative myeloproliferative neoplasm (MPN), is characterized by an increased production of platelets and an elevated risk of thrombosis. Based on mostly retrospective and observational studies, once daily low-dose aspirin is considered a standard-of-care for the treatment of patients with ET, given its inhibition of cyclooxygenase (COX)-1, an enzyme involved in the synthesis of thromboxane A2,a substance involved in platelet aggregation and blood clotting which is then converted into more stable thromboxane B2.
Nevertheless, inhibition of COX-1 has the potential to increase platelet production. Furthermore, more frequent dosing of low-dose aspirin may also inhibit the COX-2 enzyme involved in the production of prostacyclin I2 that facilitates preservation of the endothelium which itself has inhibitory effects on platelet production.
The co-primary endpoints of the dose-finding components of this multicenter, randomized, double-blind clinical trial (Aspirin Regimens in Essential Thrombocythemia [ARES]; EudraCT 2016-002885-30) were to evaluate COX-1 inhibition (using serum thromboxane B2 as a surrogate measure) and COX-2 activity (based on the prostaglandin I2 metabolite in urine) associated with different low-dose aspirin regimens in patients with ET.1,2