Risk of Atrial Fibrillation and Bleeding Diathesis Associated With Ibrutinib Treatment: A Systematic Review and Pooled Analysis of Four Randomized Controlled.

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Risk of Atrial Fibrillation and Bleeding Diathesis Associated With Ibrutinib Treatment: A Systematic Review and Pooled Analysis of Four Randomized Controlled Trials Seongseok Yun, Nicole D. Vincelette, Utkarsh Acharya, Ivo Abraham Clinical Lymphoma, Myeloma and Leukemia Volume 17, Issue 1, Pages 31-37.e13 (January 2017) DOI: 10.1016/j.clml.2016.09.010 Copyright © 2016 Elsevier Inc. Terms and Conditions

Figure 1 Trial Selection Process for Systematic Review and Pooled Analysis Clinical Lymphoma, Myeloma and Leukemia 2017 17, 31-37.e13DOI: (10.1016/j.clml.2016.09.010) Copyright © 2016 Elsevier Inc. Terms and Conditions

Figure 2 Analysis of Risk Ratio of Afib/Aflutter and Bleeding. Forest Plots of Risk Ratios for Serious Afib/Aflutter (A), All-Grade Afib/Aflutter (B), Major Bleeding (C), and All-Grade Bleeding (D) From All Available Data. Size of Data Markers (Square) Corresponds to Weight of Study in Pooled Analysis. Effects of Interventions are Calculated by Fixed Effects Model Abbreviations: Afib = atrial fibrillation; Aflutter = atrial flutter. Clinical Lymphoma, Myeloma and Leukemia 2017 17, 31-37.e13DOI: (10.1016/j.clml.2016.09.010) Copyright © 2016 Elsevier Inc. Terms and Conditions

Supplemental Figure 1 Funnel Plot Evaluating Evidence of Publication Bias. Black circle = CLL/SLL trial; green square = MCL trial Abbreviations: CLL/SLL = chronic lymphocytic leukemia/small lymphocytic leukemia; MCL = mantle-cell lymphoma. Clinical Lymphoma, Myeloma and Leukemia 2017 17, 31-37.e13DOI: (10.1016/j.clml.2016.09.010) Copyright © 2016 Elsevier Inc. Terms and Conditions

Supplemental Figure 2 Subgroup Analysis of Serious Afib/Aflutter. Forest Plots of RR Difference for Serious Afib/Aflutter From All Available Data. Size of Data Markers (Square) Corresponds to Weight of Study in Analysis. Effects of Interventions Are Calculated With Fixed Effects Model. Criteria Used for Subgroup Analysis Include Underlying Pathology, Treatment Setting, Ibrutinib Dose, and Duration of Ibrutinib Exposure Abbreviations: Afib = atrial fibrillation; Aflutter = atrial flutter. Clinical Lymphoma, Myeloma and Leukemia 2017 17, 31-37.e13DOI: (10.1016/j.clml.2016.09.010) Copyright © 2016 Elsevier Inc. Terms and Conditions

Supplemental Figure 2 Subgroup Analysis of Serious Afib/Aflutter. Forest Plots of RR Difference for Serious Afib/Aflutter From All Available Data. Size of Data Markers (Square) Corresponds to Weight of Study in Analysis. Effects of Interventions Are Calculated With Fixed Effects Model. Criteria Used for Subgroup Analysis Include Underlying Pathology, Treatment Setting, Ibrutinib Dose, and Duration of Ibrutinib Exposure Abbreviations: Afib = atrial fibrillation; Aflutter = atrial flutter. Clinical Lymphoma, Myeloma and Leukemia 2017 17, 31-37.e13DOI: (10.1016/j.clml.2016.09.010) Copyright © 2016 Elsevier Inc. Terms and Conditions

Supplemental Figure 3 Subgroup Analysis of Major Bleeding. Forest Plots of Relative Risk Difference for Major Bleeding From All Available Data. Size of Data Markers (Square) Corresponds to Weight of Study in Analysis. Effects of Interventions Are Calculated With Fixed Effects Model. Criteria Used for Subgroup Analysis Include Underlying Pathology, Treatment Setting, Ibrutinib Dose, and Duration of Ibrutinib Exposure Clinical Lymphoma, Myeloma and Leukemia 2017 17, 31-37.e13DOI: (10.1016/j.clml.2016.09.010) Copyright © 2016 Elsevier Inc. Terms and Conditions

Supplemental Figure 3 Subgroup Analysis of Major Bleeding. Forest Plots of Relative Risk Difference for Major Bleeding From All Available Data. Size of Data Markers (Square) Corresponds to Weight of Study in Analysis. Effects of Interventions Are Calculated With Fixed Effects Model. Criteria Used for Subgroup Analysis Include Underlying Pathology, Treatment Setting, Ibrutinib Dose, and Duration of Ibrutinib Exposure Clinical Lymphoma, Myeloma and Leukemia 2017 17, 31-37.e13DOI: (10.1016/j.clml.2016.09.010) Copyright © 2016 Elsevier Inc. Terms and Conditions

Supplemental Figure 4 One-Way Sensitivity Test for Primary Outcomes. One-Way Sensitivity Analyses for Serious Afib/Aflutter and Major Bleeding Were Performed by Removing a Single Study at Time. Size of Data Markers (Square) Corresponds to Weight of Study in Analysis. Effects of Interventions Are Calculated With Fixed Effects Model. Removing Single Study Did Not Affect Overall Primary Outcomes Abbreviations: Afib = atrial fibrillation; Aflutter = atrial flutter. Clinical Lymphoma, Myeloma and Leukemia 2017 17, 31-37.e13DOI: (10.1016/j.clml.2016.09.010) Copyright © 2016 Elsevier Inc. Terms and Conditions

Supplemental Figure 4 One-Way Sensitivity Test for Primary Outcomes. One-Way Sensitivity Analyses for Serious Afib/Aflutter and Major Bleeding Were Performed by Removing a Single Study at Time. Size of Data Markers (Square) Corresponds to Weight of Study in Analysis. Effects of Interventions Are Calculated With Fixed Effects Model. Removing Single Study Did Not Affect Overall Primary Outcomes Abbreviations: Afib = atrial fibrillation; Aflutter = atrial flutter. Clinical Lymphoma, Myeloma and Leukemia 2017 17, 31-37.e13DOI: (10.1016/j.clml.2016.09.010) Copyright © 2016 Elsevier Inc. Terms and Conditions

Supplemental Figure 5 Analyses Using Data From Original Reports Clinical Lymphoma, Myeloma and Leukemia 2017 17, 31-37.e13DOI: (10.1016/j.clml.2016.09.010) Copyright © 2016 Elsevier Inc. Terms and Conditions