Prolonged Proton Pump Inhibitor Use and Thrombohemorrhagic Risk in Essential Thrombocythemia and Polycythemia Vera Patients Treated with Long-Term Aspirin: A Pilot Study.

INTRODUCTION: Proton pump inhibitors (PPIs) are known to decrease the risk of gastrointestinal (GI) bleeding. However, concerns have been raised regarding the potential pharmacodynamic interactions of PPIs and antiplatelet drugs with respect to cardiovascular risk. Patients with BCR::ABL1-negative myeloproliferative neoplasms (MPNs), essential thrombocythemia (ET), and polycythemia vera (PV) often suffer from peptic ulcer disease (PUD) and frequently receive low-dose aspirin due to an intrinsically high thrombotic risk. METHOD: This retrospective multicenter study from a community setting investigated whether continuous PPI use may affect thrombohemorrhagic risk in ET and PV patients treated with long-term aspirin. RESULTS: Ninety-four aspirin-treated MPN patients (ET = 36, PV = 58) were included; median age was 69.5 years (range 21-92) and 40 (42.6%) were males. Nineteen (20.2%) patients continuously received PPIs and pantoprazole (n = 15, 78.9%) was the most frequently received PPI. PV phenotype (p = 0.085), male sex (p = 0.011), and prior thrombosis (p = 0.005) were associated with PPI use, whereas no correlations were found with respect to age, disease risk, splenomegaly, mutational status, constitutional symptoms, cardiovascular risk factors, cytoreductive treatment, or any of the blood cell counts (p > 0.050 for all analyses). The median follow-up time was 55.5 months; 19 (20.2%) thrombotic and 13 (13.8%) bleeding events occurred during this time. The use of PPIs was not associated with an increased risk of thrombosis (p = 0.158) or overall bleeding (p = 0.229) and none of the patients treated with PPIs experienced GI bleeding. CONCLUSIONS: Considering that Helicobacter pylori infection and PUD are quite frequent in ET and PV patients, these preliminary results may provide some reassurance to physicians regarding the absence of thrombohemorrhagic risk associated with prolonged PPI use in MPN patients treated with long-term aspirin. Our observations may be even more important in the light of recent evidence suggesting suboptimal platelet inhibition in ET with once-daily when compared to twice- or triple-daily aspirin which may also cause more abdominal discomfort. Limitations of this study are its retrospective design, limited number of patients included, and the lack of pharmacodynamic and pharmacokinetic assessments.

Polypharmacy, Potentially Inappropriate Medications, and Drug-to-Drug Interactions in Patients with Chronic Myeloproliferative Neoplasms.

Polypharmacy, potentially inappropriate medications (PIMs), and drug-to-drug interactions (DDIs) are highly prevalent in the elderly and may have adverse effects on health-related outcomes. Their occurrence and clinical and prognostic associations in patients with chronic myeloproliferative neoplasms (MPN) are unknown. We retrospectively evaluated polypharmacy, PIMs, and DDIs in a cohort of 124 MPN patients (essential thrombocythemia, ET = 63, polycythemia vera, PV = 44, myelofibrosis = 9, MPN unclassifiable = 8) from a single community hematology practice. There were 761 drug prescriptions with a median of five prescribed medications per patient. Polypharmacy, at least one PIM (calculated for persons >60 years of age, n = 101), and at least one DDI were recorded in 76 (61.3%), 46 (45.5%), and 77 (62.1%) of patients, respectively. Seventy-four (59.6%) and twenty-one (16.9%) patients had at least one C or at least one D interaction, respectively. Among other associations, polypharmacy and DDIs were associated with older age, management of disease-related symptoms, osteoarthritis/osteoporosis, and different CV disorders. In multivariate analyses adjusted for clinically meaningful parameters, both polypharmacy and DDIs were significantly associated with inferior overall survival (OS) and time to thrombosis (TTT), whereas PIMs had no significant associations with neither OS nor TTT. There were no associations with bleeding or transformation risks. Polypharmacy, DDIs, and PIMs are very frequent among MPN patients and may have important clinical associations.