A Comparative Analysis of Cardiovascular Events Associated With Acalabrutinib Versus Ibrutinib in Chronic Lymphocytic Leukemia: Insights From a Global Federated Network
ABSTRACT Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in adults, characterized by the accumulation of dysfunctional lymphocytes. Ibrutinib, a first‐generation Bruton tyrosine kinase (BTK) inhibitor, has significantly improved CLL treatment but is associated with adverse car...
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Wiley
2025-06-01
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| Series: | Pharmacology Research & Perspectives |
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| Online Access: | https://doi.org/10.1002/prp2.70113 |
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| author | Abdulrahman Majrashi Ying X. Gue Alena Shantsila Stella Williams Catrin Tudur Smith Gregory Y. H. Lip Andrew R. Pettitt |
| author_facet | Abdulrahman Majrashi Ying X. Gue Alena Shantsila Stella Williams Catrin Tudur Smith Gregory Y. H. Lip Andrew R. Pettitt |
| author_sort | Abdulrahman Majrashi |
| collection | DOAJ |
| description | ABSTRACT Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in adults, characterized by the accumulation of dysfunctional lymphocytes. Ibrutinib, a first‐generation Bruton tyrosine kinase (BTK) inhibitor, has significantly improved CLL treatment but is associated with adverse cardiovascular events such as atrial fibrillation (AF) and hypertension (HTN). Second‐generation BTK inhibitors (BTKi) such as acalabrutinib were developed to have greater selectivity for BTK to reduce off‐target effects and improve safety. Comparative real‐world data between ibrutinib and second‐generation BTKi are limited. This study analyzed data from the TriNetX Global Collaborative Network to compare cardiovascular outcomes in CLL patients who received ibrutinib or acalabrutinib. The two groups were well‐balanced using propensity score matching. The outcomes examined included new‐onset AF, HTN, reported heart failure, ventricular arrhythmias, bleeding, and all‐cause mortality. The incidence of AF/flutter was lower for acalabrutinib compared to ibrutinib [5.8% vs. 11.7%; HR 0.59 (95% CI 0.43–0.83); p = 0.002]. The incidence of HTN was also lower in the acalabrutinib cohort [15% vs. 26.3%; HR 0.65 (95% CI 0.53–0.81); p < 0.05]. The incidence of heart failure, ventricular arrhythmia, bleeding events, or all‐cause mortality did not differ after 3 years of treatment with acalabrutinib or ibrutinib, respectively. Our findings indicate that acalabrutinib has a more favorable cardiovascular toxicity profile compared to ibrutinib; therefore, validating the ELEVATE‐RR trial in a real‐world setting. |
| format | Article |
| id | doaj-art-3a696b8876a14f93ac2f49b4f97da564 |
| institution | OA Journals |
| issn | 2052-1707 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | Pharmacology Research & Perspectives |
| spelling | doaj-art-3a696b8876a14f93ac2f49b4f97da5642025-08-20T02:07:24ZengWileyPharmacology Research & Perspectives2052-17072025-06-01133n/an/a10.1002/prp2.70113A Comparative Analysis of Cardiovascular Events Associated With Acalabrutinib Versus Ibrutinib in Chronic Lymphocytic Leukemia: Insights From a Global Federated NetworkAbdulrahman Majrashi0Ying X. Gue1Alena Shantsila2Stella Williams3Catrin Tudur Smith4Gregory Y. H. Lip5Andrew R. Pettitt6Liverpool Centre for Cardiovascular Science at University of Liverpool Liverpool John Moores University and Liverpool Heart & Chest Hospital Liverpool UKLiverpool Centre for Cardiovascular Science at University of Liverpool Liverpool John Moores University and Liverpool Heart & Chest Hospital Liverpool UKLiverpool Centre for Cardiovascular Science at University of Liverpool Liverpool John Moores University and Liverpool Heart & Chest Hospital Liverpool UKClatterbridge Cancer Centre NHS Foundation Trust Liverpool UKDepartment of Health Data Science University of Liverpool Liverpool UKLiverpool Centre for Cardiovascular Science at University of Liverpool Liverpool John Moores University and Liverpool Heart & Chest Hospital Liverpool UKClatterbridge Cancer Centre NHS Foundation Trust Liverpool UKABSTRACT Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in adults, characterized by the accumulation of dysfunctional lymphocytes. Ibrutinib, a first‐generation Bruton tyrosine kinase (BTK) inhibitor, has significantly improved CLL treatment but is associated with adverse cardiovascular events such as atrial fibrillation (AF) and hypertension (HTN). Second‐generation BTK inhibitors (BTKi) such as acalabrutinib were developed to have greater selectivity for BTK to reduce off‐target effects and improve safety. Comparative real‐world data between ibrutinib and second‐generation BTKi are limited. This study analyzed data from the TriNetX Global Collaborative Network to compare cardiovascular outcomes in CLL patients who received ibrutinib or acalabrutinib. The two groups were well‐balanced using propensity score matching. The outcomes examined included new‐onset AF, HTN, reported heart failure, ventricular arrhythmias, bleeding, and all‐cause mortality. The incidence of AF/flutter was lower for acalabrutinib compared to ibrutinib [5.8% vs. 11.7%; HR 0.59 (95% CI 0.43–0.83); p = 0.002]. The incidence of HTN was also lower in the acalabrutinib cohort [15% vs. 26.3%; HR 0.65 (95% CI 0.53–0.81); p < 0.05]. The incidence of heart failure, ventricular arrhythmia, bleeding events, or all‐cause mortality did not differ after 3 years of treatment with acalabrutinib or ibrutinib, respectively. Our findings indicate that acalabrutinib has a more favorable cardiovascular toxicity profile compared to ibrutinib; therefore, validating the ELEVATE‐RR trial in a real‐world setting.https://doi.org/10.1002/prp2.70113acalabrutinibatrial fibrillationcardiovascular toxicitieshypertensionibrutinib |
| spellingShingle | Abdulrahman Majrashi Ying X. Gue Alena Shantsila Stella Williams Catrin Tudur Smith Gregory Y. H. Lip Andrew R. Pettitt A Comparative Analysis of Cardiovascular Events Associated With Acalabrutinib Versus Ibrutinib in Chronic Lymphocytic Leukemia: Insights From a Global Federated Network Pharmacology Research & Perspectives acalabrutinib atrial fibrillation cardiovascular toxicities hypertension ibrutinib |
| title | A Comparative Analysis of Cardiovascular Events Associated With Acalabrutinib Versus Ibrutinib in Chronic Lymphocytic Leukemia: Insights From a Global Federated Network |
| title_full | A Comparative Analysis of Cardiovascular Events Associated With Acalabrutinib Versus Ibrutinib in Chronic Lymphocytic Leukemia: Insights From a Global Federated Network |
| title_fullStr | A Comparative Analysis of Cardiovascular Events Associated With Acalabrutinib Versus Ibrutinib in Chronic Lymphocytic Leukemia: Insights From a Global Federated Network |
| title_full_unstemmed | A Comparative Analysis of Cardiovascular Events Associated With Acalabrutinib Versus Ibrutinib in Chronic Lymphocytic Leukemia: Insights From a Global Federated Network |
| title_short | A Comparative Analysis of Cardiovascular Events Associated With Acalabrutinib Versus Ibrutinib in Chronic Lymphocytic Leukemia: Insights From a Global Federated Network |
| title_sort | comparative analysis of cardiovascular events associated with acalabrutinib versus ibrutinib in chronic lymphocytic leukemia insights from a global federated network |
| topic | acalabrutinib atrial fibrillation cardiovascular toxicities hypertension ibrutinib |
| url | https://doi.org/10.1002/prp2.70113 |
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