In this large real-world TriNetX analysis of 2887 matched patients per cohort, zanubrutinib had numerically fewer AF/flutter events than acalabrutinib at one year, but time-to-event analysis showed no statistically significant difference, and hypertension, cerebral infarction, and all-cause mortality were similar, suggesting similar cardiovascular safety profiles overall (hypothesis-generating, requiring prospective validation).
One-year AF/flutter event rates were numerically lower with zanubrutinib than acalabrutinib.
Time-to-event analysis did not show a statistically significant difference in AF risk between zanubrutinib and acalabrutinib.
Binary analysis of AF/flutter showed a borderline association favoring zanubrutinib.
Cerebral infarction rates were similar between the two groups.
New-onset hypertension did not differ significantly between zanubrutinib and acalabrutinib.
All-cause mortality at one year did not differ significantly between groups.
The authors conclude the two drugs share similar cardiovascular safety profiles overall, but findings are hypothesis-generating.
This study used a large database of real-world patient records to compare two newer drugs for blood cancers such as chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenström macroglobulinemia: zanubrutinib and acalabrutinib. Both belong to a drug class (BTK inhibitors) that has caused heart rhythm problems like atrial fibrillation in older drugs of the class. The researchers matched 2887 patients on each drug based on their characteristics and followed them for one year. Atrial fibrillation or flutter occurred somewhat less often with zanubrutinib (4.05%) than with acalabrutinib (5.25%), but the statistical analyses over time did not show a clear difference (p = 0.06 and 0.05, right at the threshold). Rates of stroke-type events (cerebral infarction), new high blood pressure, and death from any cause were also not meaningfully different between the drugs. This research suggests the two drugs have broadly similar heart-related safety over one year, with a possible small advantage for zanubrutinib on atrial fibrillation that remains uncertain. Because this was a retrospective database analysis rather than a randomized trial, the authors stress the results are hypothesis-generating and need confirmation in prospective studies.
Awad M, Tah S, Ahmad S, Patel H, Kumsi Sreedhar P, Lingamsetty S, et al.. (2026). Comparative Cardiovascular Outcomes in Acalabrutinib vs. Zanubrutinib in B-Cell Malignancies: A TriNetX Data Study.. Current oncology (Toronto, Ont.). https://doi.org/10.3390/curroncol33100641