Publications by authors named "Chrisly Dillon"

18 Publications

  • Page 1 of 1

Outcomes of Individuals With and Without Heart Failure Presenting With Acute Coronary Syndrome.

Am J Cardiol 2021 06 3;148:1-7. Epub 2021 Mar 3.

Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.

Major adverse cardiac event (MACE) and bleeding risks following percutaneous coronary intervention (PCI) for acute coronary syndromes (ACS) are not well defined in individuals with heart failure (HF). We followed 1,145 individuals in the Pharmacogenomic Resource to improve Medication Effectiveness Genotype Guided Antiplatelet Therapy cohort for MACE and bleeding events following PCI for ACS. We constructed Cox proportional hazards models to compare MACE and bleeding in those with versus without HF, adjusting for sociodemographics, comorbidities, and medications. We also determined predictors of MACE and bleeding events in both groups. 370 (32%) individuals did and 775 (68%) did not have HF prior to PCI. Mean age was 61.7 ± 12.2 years, 31% were female, and 24% were African American. After a median follow-up of 0.78 years, individuals with HF had higher rates of MACE compared to those without HF (48 vs. 24 events per 100 person years) which remained significant after multivariable adjustment (hazard ratio [HR] 1.31, 95% confidence interval [CI] 1.00 to 1.72). Similarly, bleeding was higher in those with versus without HF (22 vs. 11 events per 100 person years), although this was no longer statistically significant after multivariable adjustment (HR 1.29, 95% CI 0.86 to 1.93). Diabetes and peripheral vascular disease were predictors of MACE, and end-stage renal disease was a predictor of bleeding among participants with HF. MACE risk is higher in individuals with versus without HF following PCI for ACS. However, the risk of bleeding, especially among those with end-stage renal disease , must be considered when determining post-PCI anticoagulant strategies.
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http://dx.doi.org/10.1016/j.amjcard.2021.02.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113093PMC
June 2021

Impact of the CYP2C19*17 Allele on Outcomes in Patients Receiving Genotype-Guided Antiplatelet Therapy After Percutaneous Coronary Intervention.

Clin Pharmacol Ther 2021 03 2;109(3):705-715. Epub 2020 Oct 2.

Department of Pharmacotherapy and Translational Research, Center for Pharmacogenomics and Precision Medicine, University of Florida, Gainesville, Florida, USA.

Genotyping for CYP2C19 no function alleles to guide antiplatelet therapy after percutaneous coronary intervention (PCI) improves clinical outcomes. Although results for the increased function CYP2C19*17 allele are also reported, its clinical relevance in this setting remains unclear. A collaboration across nine sites examined antiplatelet therapy prescribing and clinical outcomes in 3,342 patients after implementation of CYP2C19-guided antiplatelet therapy. Risk of major atherothrombotic and bleeding events over 12 months after PCI were compared across cytochrome P450 2C19 isozyme (CYP2C19) metabolizer phenotype and antiplatelet therapy groups by proportional hazards regression. Clopidogrel was prescribed to a similar proportion of CYP2C19 normal (84.5%), rapid (82.9%), and ultrarapid metabolizers (80.6%) (P = 0.360). Clopidogrel-treated normal metabolizers (20.4 events/100 patient-years; adjusted hazard ratio (HR) 1.00, 95% confidence interval (CI), 0.75-1.33, P = 0.993) and clopidogrel-treated rapid or ultrarapid metabolizers (19.1 events/100 patient-years; adjusted HR 0.95, 95% CI, 0.69-1.30, P = 0.734) exhibited no difference in major atherothrombotic events compared with patients treated with prasugrel or ticagrelor (17.6 events/100 patient-years). In contrast, clopidogrel-treated intermediate and poor metabolizers exhibited significantly higher atherothrombotic event risk compared with prasugrel/ticagrelor-treated patients (adjusted HR 1.56, 95% CI, 1.12-2.16, P = 0.008). When comparing clopidogrel-treated rapid or ultrarapid metabolizers to normal metabolizers, no difference in atherothrombotic (adjusted HR 0.97, 95% CI, 0.73-1.29, P = 0.808) or bleeding events (adjusted HR 1.34, 95% CI, 0.83-2.17, P = 0.224) were observed. In a real-world setting of genotype-guided antiplatelet therapy, the CYP2C19*17 allele did not significantly impact post-PCI prescribing decisions or clinical outcomes. These results suggest the CYP2C19 *1/*17 and *17/*17 genotypes have limited clinical utility to guide antiplatelet therapy after PCI.
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http://dx.doi.org/10.1002/cpt.2039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902344PMC
March 2021

Correction: Evaluating the extent of reusability of CYP2C19 genotype data among patients genotyped for antiplatelet therapy selection.

Genet Med 2020 Nov;22(11):1919

University of Florida College of Pharmacy, Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine, Gainesville, FL, USA.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41436-020-0931-1DOI Listing
November 2020

Evaluating the extent of reusability of CYP2C19 genotype data among patients genotyped for antiplatelet therapy selection.

Genet Med 2020 11 17;22(11):1898-1902. Epub 2020 Jul 17.

University of Florida College of Pharmacy, Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine, Gainesville, FL, USA.

Purpose: Genotype-guided antiplatelet therapy is increasingly being incorporated into clinical care. The purpose of this study is to determine the extent to which patients initially genotyped for CYP2C19 to guide antiplatelet therapy were prescribed additional medications affected by CYP2C19.

Methods: We assembled a cohort of patients from eight sites performingCYP2C19 genotyping to inform antiplatelet therapy. Medication orders were evaluated from time of genotyping through one year. The primary endpoint was the proportion of patients prescribed two or more CYP2C19 substrates. Secondary endpoints were the proportion of patients with a drug-genotype interaction and time to receiving a CYP2C19 substrate.

Results: Nine thousand one hundred ninety-one genotyped patients (17% nonwhite) with a mean age of 68 ± 3 years were evaluated; 4701 (51%) of patients received two or more CYP2C19 substrates and 3835 (42%) of patients had a drug-genotype interaction. The average time between genotyping and CYP2C19 substrate other than antiplatelet therapy was 25 ± 10 days.

Conclusions: More than half of patients genotyped in the setting of CYP2C19-guided antiplatelet therapy received another medication impacted by CYP2C19 in the following year. Given that genotype is stable for a patient's lifetime, this finding has implications for cost effectiveness, patient care, and treatment outcomes beyond the indication for which it was originally performed.
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http://dx.doi.org/10.1038/s41436-020-0894-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606808PMC
November 2020

Cost-effectiveness of CYP2C19-guided antiplatelet therapy in patients with acute coronary syndrome and percutaneous coronary intervention informed by real-world data.

Pharmacogenomics J 2020 10 11;20(5):724-735. Epub 2020 Feb 11.

Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, USA.

Current guidelines recommend dual antiplatelet therapy (DAPT) consisting of aspirin and a P2Y12 inhibitors following percutaneous coronary intervention (PCI). CYP2C19 genotype can guide DAPT selection, prescribing ticagrelor or prasugrel for loss-of-function (LOF) allele carriers (genotype-guided escalation). Cost-effectiveness analyses (CEA) are traditionally grounded in clinical trial data. We conduct a CEA using real-world data using a 1-year decision-analytic model comparing primary strategies: universal empiric clopidogrel (base case), universal ticagrelor, and genotype-guided escalation. We also explore secondary strategies commonly implemented in practice, wherein all patients are prescribed ticagrelor for 30 days post PCI. After 30 days, all patients are switched to clopidogrel irrespective of genotype (nonguided de-escalation) or to clopidogrel only if patients do not harbor an LOF allele (genotype-guided de-escalation). Compared with universal clopidogrel, both universal ticagrelor and genotype-guided escalation were superior with improvement in quality-adjusted life years (QALY's). Only genotype-guided escalation was cost-effective ($42,365/QALY) and demonstrated the highest probability of being cost-effective across conventional willingness-to-pay thresholds. In the secondary analysis, compared with the nonguided de-escalation strategy, although genotype-guided de-escalation and universal ticagrelor were more effective, with ICER of $188,680/QALY and $678,215/QALY, respectively, they were not cost-effective. CYP2C19 genotype-guided antiplatelet prescribing is cost-effective compared with either universal clopidogrel or universal ticagrelor using real-world implementation data. The secondary analysis suggests genotype-guided and nonguided de-escalation may be viable strategies, needing further evaluation.
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http://dx.doi.org/10.1038/s41397-020-0162-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7417282PMC
October 2020

Genetic Factors Influencing Warfarin Dose in Black-African Patients: A Systematic Review and Meta-Analysis.

Clin Pharmacol Ther 2020 06 28;107(6):1420-1433. Epub 2020 Jan 28.

Department of Molecular and Clinical Pharmacology, The Wolfson Centre for Personalized Medicine, MRC Centre for Drug Safety Science, University of Liverpool, Liverpool, UK.

Warfarin is the most commonly used oral anticoagulant in sub-Saharan Africa. Dosing is challenging due to a narrow therapeutic index and high interindividual variability in dose requirements. To evaluate the genetic factors affecting warfarin dosing in black-Africans, we performed a meta-analysis of 48 studies (2,336 patients). Significant predictors for CYP2C9 and stable dose included rs1799853 (CYP2C9*2), rs1057910 (CYP2C9*3), rs28371686 (CYP2C9*5), rs9332131 (CYP2C9*6), and rs28371685 (CYP2C9*11) reducing dose by 6.8, 12.5, 13.4, 8.1, and 5.3 mg/week, respectively. VKORC1 variants rs9923231 (-1639G>A), rs9934438 (1173C>T), rs2359612 (2255C>T), rs8050894 (1542G>C), and rs2884737 (497T>G) decreased dose by 18.1, 21.6, 17.3, 11.7, and 19.6 mg/week, respectively, whereas rs7294 (3730G>A) increased dose by 6.9 mg/week. Finally, rs12777823 (CYP2C gene cluster) was associated with a dose reduction of 12.7 mg/week. Few studies were conducted in Africa, and patient numbers were small, highlighting the need for further work in black-Africans to evaluate genetic factors determining warfarin response.
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http://dx.doi.org/10.1002/cpt.1755DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7217737PMC
June 2020

Risk of Major Adverse Cardiovascular Events and Major Hemorrhage Among White and Black Patients Undergoing Percutaneous Coronary Intervention.

J Am Heart Assoc 2019 11 8;8(22):e012874. Epub 2019 Nov 8.

Department of Neurology University of Alabama at Birmingham AL.

Background Data on racial disparities in major adverse cardiovascular events (MACE) and major hemorrhage (HEM) after percutaneous coronary intervention are limited. Factors contributing to these disparities are unknown. Methods and Results PRiME-GGAT (Pharmacogenomic Resource to Improve Medication Effectiveness-Genotype-Guided Antiplatelet Therapy) is a prospective cohort. Patients aged ≥18 years undergoing percutaneous coronary intervention were enrolled and followed for up to 1 year. Racial disparities in risk of MACE and HEM were assessed using an incident rate ratio. Sequential cumulative adjustment analyses were performed to identify factors contributing to these disparities. Data from 919 patients were included in the analysis. Compared with white patients, black patients (n=203; 22.1% of the cohort) were younger and were more likely to be female, to be a smoker, and to have higher body mass index, lower socioeconomic status, higher prevalence of diabetes mellitus and moderate to severe chronic kidney disease, and presentation with acute coronary syndrome and to undergo urgent percutaneous coronary intervention. The incident rates of MACE (34.1% versus 18.2% per 100 person-years, <0.001) and HEM (17.7% versus 10.3% per 100 person-years, =0.02) were higher in black patients. The incident rate ratio was 1.9 (95% CI, 1.3-2.6; <0.001) for MACE and 1.7 (95% CI, 1.1-2. 7; =0.02) for HEM. After adjustment for nonclinical and clinical factors, black race was not significantly associated with outcomes. Rather, differences in socioeconomic status, comorbidities, and coronary heart disease severity were attributed to racial disparities in outcomes. Conclusions Despite receiving similar treatment, racial disparities in MACE and HEM still exist. Opportunities exist to narrow these disparities by mitigating the identified contributors.
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http://dx.doi.org/10.1161/JAHA.119.012874DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6915255PMC
November 2019

Between a rock and a hard place: a high-risk patient with resistance to multiple P2Y antagonists.

Pharmacogenomics 2019 05;20(7):475-481

Department of Neurology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA 35294.

Impaired response to P2Y receptor antagonists, such as clopidogrel and prasugrel, can have devastating consequences for patients that require prolonged or indefinite therapy with these agents, including those with a left ventricular assist device (LVAD). While loss-of-function (LOF) alleles in have been elucidated as contributing to high on treatment platelet reactivity (HTPR) during clopidogrel therapy, genetic variations in the metabolic pathway of prasugrel have not been shown to elicit this same effect. Moreover, limited studies have assessed the effect of coexisting genetic variations in pharmacokinetic and pharmacodynamic pathways. Herein, we report a left ventricular assist device patient exhibiting high on treatment platelet reactivity during clopidogrel and prasugrel therapy. Genotyping revealed variants in pharmacokinetic (), and pharmacodynamic pathways, with multiple variants in P2Y, the target receptor.
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http://dx.doi.org/10.2217/pgs-2018-0201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6563016PMC
May 2019

Improvement in Kidney Function After Ventricular Assist Device Implantation and Its Influence on Thromboembolism, Hemorrhage, and Mortality.

ASAIO J 2020 03;66(3):268-276

From the Department of Neurology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.

Although heart transplantation remains the gold standard for management of heart failure, ventricular assist devices (VAD) have emerged as viable alternatives. VAD implantation improves kidney function. However, whether the improvement is sustained or associated with improved outcomes is unclear. Herein we assess kidney function improvement, predictors of improvement, and associations with thromboembolism, hemorrhage, and mortality in VAD patients. Kidney function was defined using chronic kidney disease (CKD) stages: stage 1 (glomerular filtration rate [eGFR] ≥ 90 ml/min/1.73 m), stage 2 (eGFR 60-90 ml/min/1.73 m), stage 3a (eGFR 45-59 ml/min/1.73 m), stage 3b (eGFR 30-44 ml/min/1.73 m), stage 4 (eGFR 15-30 ml/min/1.73 m), and stage 5 (eGFR < 15 ml/min/1.73 m). Improvement in kidney function was defined as an improvement in eGFR that resulted in a CKD stage change to one of lesser severity. Kidney function improved post implant, and was maintained over 1 year for all patients, except those with baseline stage 5 CKD. Younger age at implantation (OR 0.93, 95% CI: 0.90-0.96, P < 0.0001) was associated with sustained improvement in kidney function. Poor kidney function was associated increased mortality but not with thromboembolism or hemorrhage. Compared to patients with baseline eGFR > 45 ml/min/1.73 m; patients with eGFR < 45 ml/min/1.73 m had a higher mortality risk (HR 3.32, 95% CI: 1.10-9.98, p = 0.03 for stage 3b; HR 4.07, 95% CI: 1.27-13.1, p = 0.02 for stage 4; and HR 4.01, 95% CI: 1.17-13.7, p = 0.03 for stage 5 CKD). Kidney function was not associated with thromboembolism or hemorrhage, and sustained improvement was not associated with lower risk of death. However, poor kidney function at implantation was associated with an increased risk of mortality.
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http://dx.doi.org/10.1097/MAT.0000000000000989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6744354PMC
March 2020

Effect of CYP4F2, VKORC1, and CYP2C9 in Influencing Coumarin Dose: A Single-Patient Data Meta-Analysis in More Than 15,000 Individuals.

Clin Pharmacol Ther 2019 06 17;105(6):1477-1491. Epub 2019 Feb 17.

Department of Clinical Pharmacology & Genetics, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.

The cytochrome P450 (CYP)4F2 gene is known to influence mean coumarin dose. The aim of the present study was to undertake a meta-analysis at the individual patients level to capture the possible effect of ethnicity, gene-gene interaction, or other drugs on the association and to verify if inclusion of CYP4F2*3 variant into dosing algorithms improves the prediction of mean coumarin dose. We asked the authors of our previous meta-analysis (30 articles) and of 38 new articles retrieved by a systematic review to send us individual patients' data. The final collection consists of 15,754 patients split into a derivation and validation cohort. The CYP4F2*3 polymorphism was consistently associated with an increase in mean coumarin dose (+9% (95% confidence interval (CI) 7-10%), with a higher effect in women, in patients taking acenocoumarol, and in white patients. The inclusion of the CYP4F2*3 in dosing algorithms slightly improved the prediction of stable coumarin dose. New pharmacogenetic equations potentially useful for clinical practice were derived.
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http://dx.doi.org/10.1002/cpt.1323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6542461PMC
June 2019

Pharmacogenetics of warfarin dosing in patients of African and European ancestry.

Pharmacogenomics 2018 11 22;19(17):1357-1371. Epub 2018 Oct 22.

Department of Neurology, School of Medicine, University of Alabama at Birmingham, AL 35294, USA.

Despite the introduction of direct acting oral anticoagulants, warfarin remains the most commonly prescribed oral anticoagulant. However, warfarin therapy is plagued by the large inter- and intrapatient variability. The variability in dosing fueled research to identify clinical and genetic predictors and develop more accurate dosing algorithms. Observational studies have demonstrated the significant impact of single nucleotide polymorphisms in CYP2C9 and VKORC1 on warfarin dose in patients of European ancestry and African-Americans. This evidence supported the design and conduct of clinical trials to assess whether genotype-guided dosing results in improved anticoagulation control and outcomes. The trial results have shown discordance by race, with pharmacogenetic algorithms improving dose and anticoagulation control among European ancestry patients compared with African-American patients. Herein, we review the evidence from observational and interventional studies, highlight the need for inclusion of minority race groups and propose the need to develop race specific dosing algorithms.
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http://dx.doi.org/10.2217/pgs-2018-0146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6562764PMC
November 2018

Influence of Age on Warfarin Dose, Anticoagulation Control, and Risk of Hemorrhage.

Pharmacotherapy 2018 06 27;38(6):588-596. Epub 2018 Feb 27.

Department of Neurology, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.

Objective: We assessed the influence of age on warfarin dose, percentage time in target range (PTTR), and risk of major hemorrhage.

Design: Warfarin users recruited into a large prospective inception cohort study were categorized into three age groups: young (younger than 50 yrs), middle aged (50-70 yrs), and elderly (older than 70 yrs). The influence of age on warfarin dose and PTTR was assessed using regression analysis; risk of major hemorrhage was assessed using proportional hazards analysis. Models were adjusted for demographic, clinical, and genetic factors.

Setting: Two outpatient anticoagulation clinics.

Participants: A total of 1498 anticoagulated patients.

Outcomes: Warfarin dose (mg/day), PTTR, major hemorrhage.

Results: Of the 1498 patients, 22.8% were young, 44.1% were middle aged, and 33.1% were elderly. After accounting for clinical and genetic factors, compared with young warfarin users, warfarin dose requirements were 10.6% lower among the middle aged and an additional 10.6% lower for the elderly. Compared with young patients, middle-aged and elderly patients spent more time in target international normalized ratio (INR) range (p<0.0001), despite having fewer INR assessments (p<0.0001). Compared with young warfarin users, absolute risk of hemorrhage was marginally higher among the middle aged (p=0.08) and significantly higher among the elderly (p=0.016). Compared with young warfarin users, after adjustment, the relative risk of hemorrhage increased by 31% for each age category (p=0.026).

Conclusions: In a real-world setting, despite achieving better anticoagulation control, elderly patients had a higher risk of major hemorrhagic events. As the population ages and the candidacy for oral anticoagulation increases, strategies that mitigate the elevated risk of hemorrhage need to be identified.
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http://dx.doi.org/10.1002/phar.2089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6014885PMC
June 2018

Multisite Investigation of Outcomes With Implementation of CYP2C19 Genotype-Guided Antiplatelet Therapy After Percutaneous Coronary Intervention.

JACC Cardiovasc Interv 2018 01 1;11(2):181-191. Epub 2017 Nov 1.

Department of Medicine, University of Maryland, Baltimore, Maryland.

Objectives: This multicenter pragmatic investigation assessed outcomes following clinical implementation of CYP2C19 genotype-guided antiplatelet therapy after percutaneous coronary intervention (PCI).

Background: CYP2C19 loss-of-function alleles impair clopidogrel effectiveness after PCI.

Methods: After clinical genotyping, each institution recommended alternative antiplatelet therapy (prasugrel, ticagrelor) in PCI patients with a loss-of-function allele. Major adverse cardiovascular events (defined as myocardial infarction, stroke, or death) within 12 months of PCI were compared between patients with a loss-of-function allele prescribed clopidogrel versus alternative therapy. Risk was also compared between patients without a loss-of-function allele and loss-of-function allele carriers prescribed alternative therapy. Cox regression was performed, adjusting for group differences with inverse probability of treatment weights.

Results: Among 1,815 patients, 572 (31.5%) had a loss-of-function allele. The risk for major adverse cardiovascular events was significantly higher in patients with a loss-of-function allele prescribed clopidogrel versus alternative therapy (23.4 vs. 8.7 per 100 patient-years; adjusted hazard ratio: 2.26; 95% confidence interval: 1.18 to 4.32; p = 0.013). Similar results were observed among 1,210 patients with acute coronary syndromes at the time of PCI (adjusted hazard ratio: 2.87; 95% confidence interval: 1.35 to 6.09; p = 0.013). There was no difference in major adverse cardiovascular events between patients without a loss-of-function allele and loss-of-function allele carriers prescribed alternative therapy (adjusted hazard ratio: 1.14; 95% confidence interval: 0.69 to 1.88; p = 0.60).

Conclusions: These data from real-world observations demonstrate a higher risk for cardiovascular events in patients with a CYP2C19 loss-of-function allele if clopidogrel versus alternative therapy is prescribed. A future randomized study of genotype-guided antiplatelet therapy may be of value.
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http://dx.doi.org/10.1016/j.jcin.2017.07.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5775044PMC
January 2018

Anticoagulation Control in Patients With Ventricular Assist Devices.

ASAIO J 2017 Nov/Dec;63(6):759-765

From the *Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama; †Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama; ‡Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama; §Division of Cardiovascular Diseases, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama; ¶Division of Cardiothoracic Surgery, Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama; ‖Department of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama; and #Heart South Cardiovascular Group, Columbiana, Alabama.

Anticoagulation control has been associated with risk of thromboembolism and hemorrhage. Herein, we explore the relationship between anticoagulation control achieved in left ventricular assist device (LVAD) patients and evaluate the association with risk of thromboembolism and hemorrhage. Patients (19 years old or older) with a continuous flow LVAD placed from 2006 to 2012. Percent time spent in target range (PTTR) for international normalized ratio (INR) was estimated with target range of 2.0-3.0. Proportion of time spent in target range was categorized into PTTR > 60%, PTTR ≥ 50 < 60%, and PTTR < 50%. The relationship between PTTR and thromboembolism and hemorrhage was assessed. One hundred fifteen participants contributed 624.5 months of follow-up time. Only 20% of patients achieved anticoagulation control (PTTR > 60% for INR range of 2-3). After adjusting for chronic kidney disease, history of diabetes, history of atrial fibrillation, and age at implant, compared with patients with PTTR < 50%, the relative risk of thromboembolism in patients with PTTR ≥ 60% (hazard ratio [HR]: 0.37; 95% confidence interval [CI]: 0.14-0.96; p = 0.042) was significantly lower, but not for patients with a PTTR of ≥ 50 < 60% (HR: 0.21; 95% CI: 0.02-1.82; p = 0.16). The relative risk for hemorrhage was also significantly lower among patients with a PTTR ≥ 60% (HR: 0.45; 95% CI: 0.21-0.98; p = 0.045), but not among those with PTTR of ≥ 50 < 60% (HR: 0.47; 95% CI: 0.14-1.56; p = 0.22). This current study demonstrates that LVAD patients remain in the INR target range an average of 42.9% of the time. To our knowledge, this is the first report with regard to anticoagulation control as assessed by PTTR and its association with thromboembolism, hemorrhage, or death among patients with ventricular assist devices (VADs).
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http://dx.doi.org/10.1097/MAT.0000000000000592DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5662489PMC
May 2018

Predictors of Thromboembolic Events in Patients with Ventricular Assist Device.

ASAIO J 2015 Nov-Dec;61(6):640-7

From the *Department of Epidemiology, School of Public Health, †Department of Neurology, School of Medicine, ‡Division of Cardiovascular Diseases, Department of Medicine, §Division of Cardiothoracic Surgery, Department of Surgery, and ¶Department of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama.

Ventricular assist device patients (VAD) are at increased risk for thromboembolism. Biomarkers of hemolysis, such as lactate dehydrogenase (LDH) and poorly controlled international normalized ratio (INR) has been identified as predictors of thromboembolism. Patients aged 19 years and older who had a continuous flow VAD placed from 2006 to 2012 were included in this study (N = 115). We assessed the relationship of LDH elevation (≥600 IU/L) at different time points and thromboembolism. Over the 51.3 person-years of follow-up, a total of 23 first thromboembolic events occurred. Patients with elevated LDH on the day of VAD implantation had an increased risk for thromboembolism (hazard ratio [HR]: 4.72, 95% confidence interval [CI]: 1.44-15.4; p = 0.01). There was an increased risk of thromboembolism with early LDH elevation within the first month post-VAD (HR: 4.95, 95% CI: 1.69-14.4; p = 0.003) and estimated glomerular filtration rate <30 before VAD implantation (HR: 4.74, 95% CI: 1.12-20.1; p = 0.0346), whereas there was a decreased risk with good anticoagulation control (HR: 0.30, 95% CI: 0.10-0.86; p = 0.0247). Our study is the first to highlight the association between LDH elevation on the day of implantation and post-VAD thromboembolism. This study details the increased risk of thromboembolism with early LDH elevation and the importance of maintaining time in therapeutic INR range.
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http://dx.doi.org/10.1097/MAT.0000000000000284DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4631630PMC
July 2016

Paroxysmal atrial fibrillation and the hazards of under-treatment.

Int J Cardiol 2016 Jan 11;202:214-20. Epub 2015 Sep 11.

Department of Medicine, Boston Medical Center, Boston University, 801 Massachusetts Avenue, Crosstown 2, Boston, MA 02118 USA.

Background And Purpose: Oral anticoagulants are highly efficacious for the prevention of stroke in atrial fibrillation, and are the preferred treatment by current guidelines. The purpose of our study was to assess the utilization of antithrombotic drugs in atrial fibrillation patients at the time of ischemic stroke and the factors associated with their use.

Methods: We enrolled 759 consecutive patients admitted with ischemic stroke at Boston Medical Center, Geisinger Health System, and the University of Alabama. To be eligible, patients had to have electrocardiographically-confirmed atrial fibrillation at the time of admission or within 6 months of the index stroke. All stroke events and electrocardiograms were validated by study physicians. Patients with newly diagnosed atrial fibrillation were not eligible.

Results: The mean age was 78 years, 43% were male, 19% black, and the mean CHADS2 score is 3.0. Atrial fibrillation was paroxysmal in 31%. At presentation, 181 (24%) patients were taking warfarin only, 96 (13%) both warfarin and aspirin, 294 (39%) aspirin alone, and 189 (25%) no antithrombotic therapy. The mean international normalized ratio was 1.6. Among patients with paroxysmal atrial fibrillation, one in five was taking warfarin. Although increasing stroke risk was associated with a greater likelihood of warfarin use, only 39% of highest risk CHADS2 3-6 were taking warfarin at the time of stroke.

Conclusions: Among high-risk individuals with atrial fibrillation, only 37% were taking warfarin at the time of stroke. Paroxysmal atrial fibrillation was associated with the highest risk of not receiving warfarin.
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http://dx.doi.org/10.1016/j.ijcard.2015.09.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5527994PMC
January 2016

Validity of international classification of disease codes to identify ischemic stroke and intracranial hemorrhage among individuals with associated diagnosis of atrial fibrillation.

Circ Cardiovasc Qual Outcomes 2015 Jan 13;8(1):8-14. Epub 2015 Jan 13.

From the Department of Clinical and Administrative Sciences, Notre Dame of Maryland University School of Pharmacy, Baltimore (J.L.T.); Department of Neurology, University of Alabama at Birmingham (C.D., N.A.L.); Department of Medicine, Boston University Medical Center, MA (L.H., E.M.H.); Department of Biostatistics (Y.T.) and Date Coordinating Center (E.K.Q), Boston University School of Public Health, Boston, MA; and Department of Cardiology, Geisinger Health System, Danville, PA (K.B.F., P.B.B).

Background: Because of its association with death and disability, stroke is a focus of outcomes in atrial fibrillation (AF) research. International Classification of Disease-Ninth Revision (ICD-9) edition codes are commonly used to identify stroke in research, particularly in large administrative data. We sought to assess the validity of ICD-9 codes in stroke case ascertainment and for AF across 3 institutions.

Methods And Results: Participating centers included Boston Medical Center (safety net hospital), Geisinger Health System (rural Pennsylvania), and the University of Alabama (academic center in the southeastern stroke belt). ICD-9 codes for ischemic stroke (433-434, 436) and intracranial hemorrhage (430-432) identified 1812 stroke cases with an associated code for AF (427.31) from 2006 to 2010. Cases were vetted through chart review with final adjudication by a stroke neurologist. Review considered 94.2% of ICD-9 identified stroke cases valid with decreased accuracy for concurrent AF diagnosis (82.28%) and stroke attributable to AF (72.8%). Among events with "without infarction" modifiers, 7.2% were valid strokes. ICD-9 stroke code accuracy did not differ by stroke type or site. Stroke code 434 displayed higher accuracy than 433 (94.4% versus 85.2%; P<0.01), and primary stroke codes were more accurate than nonprimary codes (97.2% versus 83.7%; P<0.0001).

Conclusions: Using ICD-9 stroke and AF codes to identify patients with stroke plus AF resulted in inaccuracies. Given the expanded financial and policy implications of patient-oriented research, conclusions derived solely from administrative data without validation of outcome events should be interpreted with caution.
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http://dx.doi.org/10.1161/CIRCOUTCOMES.113.000371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4654947PMC
January 2015
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