Abstract:
BACKGROUND:Ibrutinib has revolutionized treatment for several B-cell malignancies. However, a recent clinical trial where ibrutinib was used in a front-line setting showed increased mortality during treatment compared with conventional chemotherapy. Cardiovascular toxicities were suspected as the culprit but not directly assessed in the study. OBJECTIVES:The purpose of this study was to identify and characterize cardiovascular adverse drug reactions (CV-ADR) associated with ibrutinib. METHODS:This study utilized VigiBase (International pharmacovigilance database) and performed a disproportionality analysis using reporting odds ratios (ROR) and information component (IC) to determine whether CV-ADR and CV-ADR deaths were associated with ibrutinib. IC compares observed and expected values to find associations between drugs and adverse drug reactions using disproportionate Bayesian-reporting; IC025 (lower end of the IC 95% credibility interval) >0 is significant. RESULTS:This study identified 303 ibrutinib-associated cardiovascular deaths. Ibrutinib was associated with higher reporting of supraventricular arrhythmias (SVAs) (ROR: 23.1; 95% confidence interval: 21.6 to 24.7; p < 0.0001; IC025: 3.97), central nervous system (CNS) hemorrhagic events (ROR: 3.7; 95% confidence interval: 3.4 to 4.1; p < 0.0001; IC025: 1.63), heart failure (ROR: 3.5; 95% confidence interval: 3.1 to 3.8; p < 0.0001; IC025: 1.46), ventricular arrhythmias (ROR: 4.7; 95% confidence interval: 3.7 to 5.9; p < 0.0001; IC025: 0.96), conduction disorders (ROR: 3.5; 95% confidence interval: 2.7 to 4.6; p < 0.0001; IC025: 0.76), CNS ischemic events (ROR: 2.2; 95% confidence interval: 2.0 to 2.5; p < 0.0001; IC025: 0.73), and hypertension (ROR: 1.7; 95% confidence interval: 1.5 to 1.9; p < 0.0001; IC025: 0.4). CV-ADR often occurred early after ibrutinib administration. Importantly, CV-ADR were associated with fatalities that ranged from ∼10% (SVAs and ventricular arrhythmias) to ∼20% (CNS events, heart failure, and conduction disorders). Ibrutinib-associated SVA portends poor prognosis when CNS events occur concomitantly, with 28.8% deaths (15 of 52 cases). CONCLUSIONS:Severe and occasionally fatal cardiac events occur in patients exposed to ibrutinib. These events should be considered in patient care and in clinical trial designs. (Evaluation of Reporting of Cardio-vascular Adverse Events With Antineoplastic and Immunomodulating Agents [EROCA]; NCT03530215).
journal_name
J Am Coll Cardioljournal_title
Journal of the American College of Cardiologyauthors
Salem JE,Manouchehri A,Bretagne M,Lebrun-Vignes B,Groarke JD,Johnson DB,Yang T,Reddy NM,Funck-Brentano C,Brown JR,Roden DM,Moslehi JJdoi
10.1016/j.jacc.2019.07.056subject
Has Abstractpub_date
2019-10-01 00:00:00pages
1667-1678issue
13eissn
0735-1097issn
1558-3597pii
S0735-1097(19)36155-8journal_volume
74pub_type
杂志文章abstract::Certain clinical and cardiac morphologic findings are described in 22 patients, aged 45 to 80 years (mean 64) (15 men [68%]), in whom rupture of a papillary muscle occurred during acute myocardial infarction. In most, the acute infarction associated with papillary muscle rupture was a first coronary event (only 18% ha...
journal_title:Journal of the American College of Cardiology
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abstract::A new model for analyzing the major effects of the use of any laser angioplasty system is described. Changes in any of the six major determinants of effect (energy, duration, wavelength, medium, absorption, geometry) can be evaluated. In this report a neodymium: yttrium aluminum garnet (Nd:YAG) laser was used to make ...
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更新日期:2005-03-15 00:00:00
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更新日期:2015-09-01 00:00:00
abstract:OBJECTIVES:We investigated whether use of low-dose enteric-coated (EC) aspirin for secondary prevention of cardiovascular events has sufficient bioavailability to achieve complete platelet cyclooxygenase (COX) inhibition in all individuals. BACKGROUND:Aspirin reduces cardiovascular morbidity and mortality in patients ...
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更新日期:2005-10-04 00:00:00
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更新日期:2004-09-01 00:00:00
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更新日期:2010-05-18 00:00:00
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pub_type: 杂志文章,多中心研究
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更新日期:2015-05-19 00:00:00
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journal_title:Journal of the American College of Cardiology
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更新日期:2002-10-16 00:00:00
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journal_title:Journal of the American College of Cardiology
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更新日期:2006-11-07 00:00:00
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doi:10.1016/s0735-1097(98)00037-0
更新日期:1998-04-01 00:00:00
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journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/s0735-1097(84)80293-4
更新日期:1984-06-01 00:00:00
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journal_title:Journal of the American College of Cardiology
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doi:10.1016/j.jacc.2011.05.018
更新日期:2011-08-16 00:00:00
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更新日期:2006-12-05 00:00:00
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更新日期:2001-04-01 00:00:00
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更新日期:2001-04-01 00:00:00
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doi:10.1016/j.jacc.2005.08.060
更新日期:2006-01-17 00:00:00
abstract:OBJECTIVES:This study investigated the effect of age and gender on central arterial hemodynamic variables derived from noninvasive tonometric carotid pressure waveforms. BACKGROUND:Women have a greater age-related increase in left ventricular (LV) mass than do men and are more likely to experience symptomatic heart fa...
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pub_type: 杂志文章
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更新日期:1997-12-01 00:00:00
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journal_title:Journal of the American College of Cardiology
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doi:10.1016/j.jacc.2007.06.016
更新日期:2007-09-18 00:00:00
abstract::Frequency analysis with fast Fourier transform and time domain analysis after signal averaging of the electrocardiogram (ECG) have given contradictory results in patients with sustained ventricular tachycardia after myocardial infarction. Therefore, the same orthogonal ECGs were analyzed in the frequency domain (Black...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/0735-1097(88)90368-3
更新日期:1988-07-01 00:00:00
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更新日期:2003-07-02 00:00:00
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pub_type: 临床试验,杂志文章
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更新日期:2004-12-21 00:00:00