Cardiovascular Risk Associated With Ibrutinib Use in Chronic Lymphocytic Leukemia: A Population-Based Cohort Study
Autor: | Douglas S. Lee, Anca Prica, Peter C. Austin, Andrea Pang, Paaladinesh Thavendiranathan, Husam Abdel-Qadir, Darryl P. Leong, Oscar Calvillo-Argüelles, Nasruddin Sabrie, Kumaraswamy Nanthakumar |
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Rok vydání: | 2021 |
Předmět: |
Male
Canada Cancer Research medicine.medical_specialty Chronic lymphocytic leukemia MEDLINE Cohort Studies chemistry.chemical_compound Population based cohort Piperidines Risk Factors Internal medicine medicine Humans Aged Aged 80 and over business.industry Adenine Incidence Atrial fibrillation Prognosis medicine.disease Leukemia Lymphocytic Chronic B-Cell Hospitalization Survival Rate Oncology chemistry Cardiovascular Diseases Heart Disease Risk Factors Case-Control Studies Ibrutinib Heart failure Female business Follow-Up Studies |
Zdroj: | Journal of Clinical Oncology. 39:3453-3462 |
ISSN: | 1527-7755 0732-183X |
Popis: | PURPOSE Ibrutinib reduces mortality in chronic lymphocytic leukemia (CLL). It increases the risk of atrial fibrillation (AF) and bleeding and there are concerns about heart failure (HF) and central nervous system ischemic events. The magnitude of these risks remains poorly quantified. METHODS Using linked administrative databases, we conducted a population-based cohort study of Ontario patients who were treated for CLL diagnosed between 2007 and 2019. We matched ibrutinib-treated patients with controls treated with chemotherapy but unexposed to ibrutinib on prior AF, age ≥ 66 years, anticoagulant exposure, and propensity for receiving ibrutinib. Study outcomes were AF-related health care contact, hospital-diagnosed bleeding, new diagnoses of HF, and hospitalizations for stroke and acute myocardial infarction (AMI). The cumulative incidence function was used to estimate absolute risks. We used cause-specific regression to study the association of ibrutinib with bleeding rates, while adjusting for anticoagulation as a time-varying covariate. RESULTS We matched 778 pairs of ibrutinib-treated and unexposed patients with CLL (N = 1,556). The 3-year incidence of AF-related health care contact was 22.7% (95% CI, 19.0 to 26.6) in ibrutinib-treated patients and 11.7% (95% CI, 9.0 to 14.8) in controls. The 3-year risk of hospital-diagnosed bleeding was 8.8% (95% CI, 6.5 to 11.7) in ibrutinib-treated patients and 3.1% (95% CI, 1.9 to 4.6) in controls. Ibrutinib-treated patients were more likely to start anticoagulation after the index date. After adjusting for anticoagulation as a time-varying covariate, ibrutinib remained positively associated with bleeding (HR, 2.58; 95% CI, 1.76 to 3.78). The 3-year risk of HF was 7.7% (95% CI, 5.4 to 10.6%) in ibrutinib-treated patients and 3.6% (95% CI, 2.2 to 5.4) in controls. There was no significant difference in the risk of ischemic stroke or AMI. CONCLUSION Ibrutinib is associated with higher risk of AF, bleeding, and HF, but not AMI or stroke. |
Databáze: | OpenAIRE |
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