Cardiovascular safety outcomes of chronic lymphocytic leukemia treatments: A systematic and targeted literature review

Chronic lymphocytic leukemia (CLL) treatments, such as targeted agents, chemotherapies, and immunotherapies, may be associated with adverse cardiovascular (CV) outcomes. To understand the extent to which CV outcomes are driven by treatment and potential differences among treatments, we conducted a systematic literature review (SLR) of interventional trials and a targeted literature review (TLR) of observational studies indexed in Embase and MEDLINE from January 2012-June 2023. CV outcomes data were sparse and heterogeneous in the SLR trials (n = 55). The incidence of atrial fibrillation was most consistently reported across clinical trials and the highest annualized incidence rates were observed with ibrutinib (range: 19.9-80.8 cases per 1000 patient-years). Among TLR observational studies (n = 24), in CLL, CV risk increased with age, baseline risk was similar to that in matched comparators without CLL, and ibrutinib conferred a higher risk than chemotherapy. Because CLL primarily affects older individuals, given their increased baseline CV risk, treatment-emergent CV events are usually multifactorial. Studies that consistently collect and report CV comorbidities, CV adverse events, and treatment outcomes are needed to clarify the relative contributions of these factors.