Efficacy and Safety of Primary Antithrombotic Prophylaxis with Ticlopidine and with Aspirin In Patients with Essential Thrombocythemia and Polycythemia Vera. Results from a Cohort Study.
Authors: Ruggeri Marco , Tosetto Alberto , Bolgan Irene , Rodeghiero Francesco 
Published: April 2020

Background. Essential Thrombocythemia (ET) and Polycythemia Vera (PV) are two chronic myeloproliferative diseases with prolonged survival, but with a high rate of vascular complications, mainly arterial thrombosis (AT). For this reason, clinical guidelines recommend the use of aspirin for primary and secondary prophylaxis. There are no data on the efficacy and safety of tienopyridine antiplatelet drugs (ticlopidine, clopidogrel), which could be useful alternatives in patients with contraindication or when aspirin is unable to prevent thrombotic event.

Aims. To estimate the frequency of thrombotic and hemorrhagic complications, in ET and PV patients treated with ticlopidine in comparison with patients taking aspirin, in single institution, prospective cohort study.

Patients and method. Data from 246 PV (143 males, 58%), median age at diagnosis 63 years (range 20–89) and 339 ET (114 males, 33.6%) patients, median age 62 (range 20–95) consecutively diagnosed from 1985 to 2005 were analyzed. Risk factors for arterial thrombosis (diabetes mellitus, arterial hypertension, hypercholesterolemia, smoking, cardiovascular disease, previous AT) were present in around 30% of patients. At diagnosis, median values of hemoglobin, leukocyte and platelet level in ET and PV were 137 and 180 g/L, 9.3 and 11 x 109/L, 888 and 582 x 109/L, respectively. After diagnosis, aspirin (100–300 mg daily) was given to 270 patients (155 ET, 57%), in 70 of them (25%) for secondary prophylaxis; ticlopidine (250 mg twice day) was administered to 84 patients with a previous history of gastric ulcer, gastritis or allergy to ASA (48 ET, 57%), in 19 of them (22%) for secondary prophylaxis. In 216 (137 ET, 63%) patients no antiplatelet drug was given. The two treated group had similar cardiovascular risk profile, higher than in those untreated. Cytoreductive treatment was given to 87 (32%) patients in ASA, 14 (17%) in ticlopidine and 61 (28%) in those not on antiplatelet treatment (p=0.02). An higher percentage of patients received hydroxyurea in ASA group compared with ticlopidine (19.6% vs 8.6%). Warfarin was administered to 10 patients for atrial fibrillation or venous thrombosis (not analyzed). 2 cases were lost from follow-up. All PV patients were phlebotomized to reduce hematocrit level.

Results. After a median follow-up of 7.8 years (very similar in the 3 groups of patients), 29 (14.5%) thrombotic events (5 fatal) among 200 ASA patients and 18 (27.7%, 1 fatal) among 65 ticlopidine patients treated for primary prophylaxis were recorded (p=0.016). In 216 not-treated patients, 40 (18.5%) thromboses were recorded. Major hemorrhages (need of transfusions, surgical intervention or hospital admission) were 17 (8.5%) in ASA, 8 (12.3%) in ticlopidine (p= 0.299) and 25 (11.6%)) in not-treated patients (p= 0.392 between antiplatelet treated and not treated patients). Thrombotic rates for patients in primary prophylaxis were 0.4%, 0.8% and 2.5% in patients on ASA, ticlopidine and not-treated, respectively.

Conclusion. In a cohort of ET and PV patients, ASA therapy appears more effective than ticlopidine in the primary prevention of thrombosis, without a significative increase of hemorrhagic risk in comparison with ticlopidine or untreated patients. This increased efficacy should be further investigated by stratifying patients accordingly to cytoreductive treatment.