Ibrutinib and Acalabrutinib Use and Risk of Atrial Fibrillation in Patients With Chronic B-cell Malignancies
NCT Number: NCT06561243
Status: ACTIVE_NOT_RECRUITING
Study Type: OBSERVATIONAL
Conditions: Chronic B-cell Malignancies|BTK Inhibitors|Cardiovascular Diseases
Interventions: DRUG: BTK inhibitor (Ibrutinib or Acalabrutinib)
Sponsor: University Hospital, Caen
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 15000
Study Design: Observational Model: |Time Perspective: p
Start Date: 2024-07-25
Completion Date: 2024-10-30
Locations: Caen University Hospital, Department of Pharmacology, Caen, Normandie, France

Summary:
Background. Ibrutinib 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 ibrutinib 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 ibrutinib or acalabrutinib. Patients will be divided into 2 groups based on ibrutinib or acalabrutinib exposure. After propensity score matching (PSM), hazard ratios (HRs) and their associated 95% confidence intervals (CIs) will be used to compare AF risk during follow-up between the matched 2 groups.

Primary Outcome Measures: Risk of incident atrial fibrillation in patients exposed to ibrutinib compared with those exposed to acalabrutinib in the whole matched cohort., ICD-10-CM code I48 will be used to identify AF during follow-up, from the introduction of the BTK inhibitor and up to 120 months
Secondary Outcome Measures: Risk of incident atrial fibrillation in patients exposed to ibrutinib compared with those exposed to acalabrutinib in a matched cohort restricted to patients aged ≤75 and to patients aged >75, ICD-10-CM code I48 will be used to identify AF during follow-up, from the introduction of the BTK inhibitor and up to 120 months|Risk of incident atrial fibrillation in patients exposed to ibrutinib compared with those exposed to acalabrutinib in a matched cohort categorized according their baseline cardiovascular risk level for developing AF, ICD-10-CM code ill be used to identify AF during follow-up, from the introduction of the BTK inhibitor and up to 120 months|Risk of all-cause mortality in patients exposed to ibrutinib compared with those exposed to acalabrutinib in the whole matched cohort, death from any cause during follow-up, from the introduction of the BTK inhibitor and up to 120 months|Risk of incident intra-cerebral hemorrhage in patients exposed to ibrutinib compared with those exposed to acalabrutinib in the whole matched cohort, ICD-10-CM code ill be used to identify intra-cerebral hemorrhage during follow-up, from the introduction of the BTK inhibitor and up to 120 months|Risk of incident major bleeding in patients exposed to ibrutinib compared with those exposed to acalabrutinib in the whole matched cohort, ICD-10-CM code ill be used to identify major bleeding during follow-up, from the introduction of the BTK inhibitor and up to 120 months|Risk of incident hypertension in patients exposed to ibrutinib compared with those exposed to acalabrutinib in the whole matched cohort, ICD-10-CM code ill be used to identify hypertension during follow-up, from the introduction of the BTK inhibitor and up to 120 months|Risk of incident MACE (composite) in patients exposed to ibrutinib compared with those exposed to acalabrutinib in the whole matched cohort, ICD-10-CM code ill be used to identify MACE (composite of acute myocardial infraction, ischemic stroke or thromboembolism and heart failure) during follow-up, from the introduction of the BTK inhibitor and up to 120 months|Risk of incident ventricular tachycardia/ventricular fibrillation/cardiac arrest (composite) in patients exposed to ibrutinib compared with those exposed to acalabrutinib in the whole matched cohort, ICD-10-CM code ill be used to identify VT/VF/cardiac arrest (composite of ventricular tachycardia, ventricular fibrillation and cardiac arrest) during follow-up, from the introduction of the BTK inhibitor and up to 120 months