Evaluating the Safety of Combining Tyrosine Kinase Inhibitors with Anticoagulants in Chronic Myeloid Leukemia: A Systematic Review.
Academic Article
Overview
abstract
INTRODUCTION: The prognosis of chronic myeloid leukemia (CML) has been revolutionized in recent decades with tyrosine kinase inhibitors (TKIs). Yet, comorbidities that require anticoagulation therapy pose a challenge in CML management because of the scarcity of evidence on the optimal drug combinations. This systematic review (SR) aims to summarize the efficacy and safety considerations for the concomitant use of anticoagulants with different TKIs in CML and investigate their potential drug interactions. METHODS: A comprehensive search strategy was used, employing Medical Subject Headings (MeSH) and free text terms across databases including PubMed (via OVID), Medline (via OVID), Embase (via OVID), and Web of Science. Members of the research team independently screened the titles and abstracts for eligibility based on predefined inclusion and exclusion criteria. Data extraction was then performed using a standardized form to record the studies' characteristics, the TKIs and anticoagulants used, and the outcomes related to safety. Two reviewers independently assessed study quality using Critical Appraisal Skills Program (CASP) checklists and the Joanna Briggs Institute (JBI) tool for case reports. RESULTS: The search yielded 406 studies, of which 13 met the inclusion criteria for reporting real-world safety data in adults receiving TKIs with anticoagulants. Overall, the combinations of TKIs with anticoagulants like ponatinib with apixaban and imatinib with warfarin had no major bleeding complications. The pharmacokinetic findings suggested some interaction variability, particularly between nilotinib and warfarin, but overall, anticoagulant use appeared safe in the studied populations across various indications for anticoagulation. CONCLUSION: This is the first systematic review that addresses a critical gap in the literature by systematically evaluating the safety profiles of various TKIs in combination with different anticoagulants. The findings from cohort studies highlighted the feasibility of concomitant use of anticoagulants and TKIs in CML patients, with close monitoring of potential adverse events and drug interactions. PROSPERO registration number: CRD42024528737.
