Comparative Cardiovascular Outcomes in Acalabrutinib vs. Zanubrutinib in B-Cell Malignancies: A TriNetX Data Study.
6 affiliations
- 1Department of Cardiology, West Virginia University Heart and Vascular Institute, Morgantown, WV 26506, USA.
- 2Department of Medicine, West Virginia University, Parkersburg, WV 26104, USA.
- 3Department of Medicine, West Virginia University, Morgantown, WV 26506, USA.
- 4Department of Medicine, Willis Knighton Health System, Shreveport, LA 71103, USA.
- 5Department of Internal Medicine, Mamata Medical College, Khammam 507002, Telangana, India.
- 6Department of Internal Medicine, Division of Cardiology, Indiana University, Indianapolis, IN 46202, USA.
Abstract
Next-generation Bruton's tyrosine kinase inhibitors (BTKis) such as acalabrutinib and zanubrutinib have improved treatment outcomes in B-cell malignancies, including chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), and Waldenström macroglobulinemia (WM), while reducing off-target toxicities compared to ibrutinib. However, their comparative cardiovascular safety profiles remain poorly characterized. This study evaluates real-world cardiovascular and clinical outcomes between zanubrutinib and acalabrutinib using a large multi-center database. We conducted a retrospective cohort study using the TriNetX Research Network (October 2017-December 2024) including adult patients with CLL, MCL, WM, or small B-cell lymphoma treated with zanubrutinib or acalabrutinib. Patients with prior exposure to other BTKis were excluded. After 1:1 propensity score matching, 2887 patients were included in each cohort. We assessed one-year outcomes including new-onset atrial fibrillation/flutter, cerebral infarction, hypertension, and all-cause mortality using Cox proportional hazards modeling. The rate of AF/flutter events observed in the zanubrutinib group (4.05%) was numerically lower compared to the acalabrutinib group (5.25%). Time-to-event analysis did not demonstrate a statistically significant difference in AF risk over time (HR 0.777, 95% CI 0.597-1.012; p = 0.06), which was similar in binary analysis (OR 0.761, 95% CI 0.581-0.997; p = 0.05). Cerebral infarction rates were similar between groups (1.09% vs. 1.12%), with no significant difference in time-to-event analysis (HR 0.984, 95% CI 0.596-1.626; p = 0.95) or binary analysis (p = 0.91). There was no significant difference in onset of hypertension in the zanubrutinib cohort (HR 1.199, 95% CI 0.957-1.501; p = 0.11) All-cause mortality was not statistically significant between the two groups (HR 0.865, 95% CI 0.740-1.012; p = 0.07). In this large, real-world analysis, fewer AF/flutter events were observed with zanubrutinib at one year; however, time-to-event analysis did not demonstrate a statistically significant difference in AF risk over time. Notably, hypertension, cerebral infarction, and all-cause mortality occurred at similar rates. This suggests zanubrutinib and acalabrutinib share similar cardiovascular safety profiles overall. However these findings are hypothesis-generating and require prospective validation before definitive conclusions about cardiovascular risk can be drawn.
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BibTeX
@article{awad2026comparative,
title = {{Comparative Cardiovascular Outcomes in Acalabrutinib vs. Zanubrutinib in B-Cell Malignancies: A TriNetX Data Study.}},
author = {Maan Awad and Sunanda Tah and Syed Ahmad and Het Patel and Prajwal Kumsi Sreedhar and Shanmukh Sai Pavan Lingamsetty and Abdulrahman Murshid and Brijesh Patel},
journal = {Current oncology (Toronto, Ont.)},
year = {2026},
month = oct,
doi = {10.3390/curroncol33100641},
url = {https://europepmc.org/article/MED/42930208},
note = {CC BY},
}
RIS
TY - JOUR
TI - Comparative Cardiovascular Outcomes in Acalabrutinib vs. Zanubrutinib in B-Cell Malignancies: A TriNetX Data Study.
AU - Maan Awad
AU - Sunanda Tah
AU - Syed Ahmad
AU - Het Patel
AU - Prajwal Kumsi Sreedhar
AU - Shanmukh Sai Pavan Lingamsetty
AU - Abdulrahman Murshid
AU - Brijesh Patel
PY - 2026
DA - 2026/10/21
JO - Current oncology (Toronto, Ont.)
DO - 10.3390/curroncol33100641
UR - https://europepmc.org/article/MED/42930208
AB - Next-generation Bruton's tyrosine kinase inhibitors (BTKis) such as acalabrutinib and zanubrutinib have improved treatment outcomes in B-cell malignancies, including chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), and Waldenström macroglobulinemia (WM), while reducing off-target toxicities compared to ibrutinib. However, their comparative cardiovascular safety profiles remain poorly characterized. This study evaluates real-world cardiovascular and clinical outcomes between zanubrutinib and acalabrutinib using a large multi-center database. We conducted a retrospective cohort study using the TriNetX Research Network (October 2017-December 2024) including adult patients with CLL, MCL, WM, or small B-cell lymphoma treated with zanubrutinib or acalabrutinib. Patients with prior exposure to other BTKis were excluded. After 1:1 propensity score matching, 2887 patients were included in each cohort. We assessed one-year outcomes including new-onset atrial fibrillation/flutter, cerebral infarction, hypertension, and all-cause mortality using Cox proportional hazards modeling. The rate of AF/flutter events observed in the zanubrutinib group (4.05%) was numerically lower compared to the acalabrutinib group (5.25%). Time-to-event analysis did not demonstrate a statistically significant difference in AF risk over time (HR 0.777, 95% CI 0.597-1.012; p = 0.06), which was similar in binary analysis (OR 0.761, 95% CI 0.581-0.997; p = 0.05). Cerebral infarction rates were similar between groups (1.09% vs. 1.12%), with no significant difference in time-to-event analysis (HR 0.984, 95% CI 0.596-1.626; p = 0.95) or binary analysis (p = 0.91). There was no significant difference in onset of hypertension in the zanubrutinib cohort (HR 1.199, 95% CI 0.957-1.501; p = 0.11) All-cause mortality was not statistically significant between the two groups (HR 0.865, 95% CI 0.740-1.012; p = 0.07). In this large, real-world analysis, fewer AF/flutter events were observed with zanubrutinib at one year; however, time-to-event analysis did not demonstrate a statistically significant difference in AF risk over time. Notably, hypertension, cerebral infarction, and all-cause mortality occurred at similar rates. This suggests zanubrutinib and acalabrutinib share similar cardiovascular safety profiles overall. However these findings are hypothesis-generating and require prospective validation before definitive conclusions about cardiovascular risk can be drawn.
SN - 1198-0052
SN - 1718-7729
ER -