Zanubrutinib and Acalabrutinib Use and Risk of Atrial Fibrillation in Patients With Chronic B-cell Malignancies

Background. Zanubrutinib and acalabrutinib are both associated with an increased risk of atrial fibrillation (AF) but AF comparative risk between these 2 BTK inhibitors (BTKis) remains largely unknown.

Objectives. Our aim was to examine the risk of developing incident AF with zanubrutinib exposure compared with acalabrutinib exposure.

Methods. Using the TriNetX research network database, authors will conduct a retrospective cohort analysis of deidentified, aggregate adult patients with chronic B-cell malignancies and exposed to zanubrutinib or acalabrutinib. Patients will be divided into 2 groups based on zanubrutinib or acalabrutinib exposure. After propensity score matching (PSM), Cox proportional hazard models will be used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) to compare the 2 matched groups. The appropriateness of the proportional hazard assumption will be examined and risk differences (RDs) will be used if appropriate. Results will summarized with the use of Kaplan-Meier survival curves.

Study Overview

• Status: Not yet recruiting
• Conditions: Cardiovascular Diseases; Chronic B-cell Malignancies; BTK Inhibitors
• Intervention / Treatment: Drug: Zanubrutinib; Drug: Acalabrutinib

• Study Type: Observational
• Enrollment (Estimated): 15000

Contacts and Locations

• Study Contact: Name: Joachim Alexandre, MD, PhD; Phone Number: +33231064670; Email: alexandre-j@chu-caen.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

adult patients - diagnose with chronic B-cell malignancies expose to zanubrutinib or acalabrutinib in the TrinetX database

Description

Inclusion Criteria:

• adult patients
• diagnose with chronic B-cell malignancies
• exposed to zanubrutinib or acalabrutinib

Exclusion Criteria:

• none

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Acalabrutinib; Adult patients with a chronic B-cell malignancy exposed to acalabrutinib	Drug: Acalabrutinib; Adult patients with a chronic B-cell malignancy exposed to acalabrutinib
Zanubrutinib; Adult patients with a chronic B-cell malignancy exposed to zanubrutinib	Drug: Zanubrutinib; Adult patients with a chronic B-cell malignancy exposed to zanubrutinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Risk of incident atrial fibrillation in patients exposed to zanubrutinib compared with those exposed to acalabrutinib in the matched cohort.	from the introduction of the BTK inhibitor and up to 5 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Risk of all-cause mortality in patients exposed to zanubrutinib compared with those exposed to acalabrutinib in thematched cohort	from the introduction of the BTK inhibitor and up to 5 years
Risk of incident intra-cerebral hemorrhage in patients exposed to zanubrutinib compared with those exposed to acalabrutinib in the matched cohort	from the introduction of the BTK inhibitor and up to 5 years
Risk of incident major bleeding in patients exposed to zanubrutinib compared with those exposed to acalabrutinib in the matched cohort	from the introduction of the BTK inhibitor and up to 5 years
Risk of incident hypertension in patients exposed to zanubrutinib compared with those exposed to acalabrutinib in the matched cohort	from the introduction of the BTK inhibitor and up to 5 years
Risk of incident MACE (composite) in patients exposed to zanubrutinib compared with those exposed to acalabrutinib in the matched cohort	from the introduction of the BTK inhibitor and up to 5 years
Risk of incident ventricular tachycardia/ventricular fibrillation/cardiac arrest (composite) in patients exposed to zanubrutinib compared with those exposed to acalabrutinib in the matched cohort	from the introduction of the BTK inhibitor and up to 5 months

Collaborators and Investigators

• Sponsor: University Hospital, Caen

Study record dates

Study Major Dates

• Study Start (Estimated): December 22, 2025
• Primary Completion (Estimated): January 15, 2026
• Study Completion (Estimated): March 31, 2026

Study Registration Dates

• First Submitted: November 26, 2025
• First Submitted That Met QC Criteria: December 12, 2025
• First Posted (Actual): December 16, 2025

Study Record Updates

• Last Update Posted (Actual): December 16, 2025
• Last Update Submitted That Met QC Criteria: December 12, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; zanubrutinib; acalabrutinib
• Other Study ID Numbers: Pharmaco111525

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Actually, data from TrinetX are only freely available for health care organizations participating to the health research network database.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No