Thyroid Hormone Therapy and Incident Stroke

Abstract Context Stroke is a leading cause of death and disability and there is a need to identify modifiable risk factors. Objective Determine the relationship between thyroid hormone treatment intensity and incidence of atrial fibrillation and stroke. Design Retrospective cohort study using data from the Veterans Health Administration between 2004 and 2017, with a median follow-up of 59 months. Setting Population-based. Participants 733,208 thyroid hormone users aged ≥18 years with at least two thyroid stimulating hormone (TSH) measurements between thyroid hormone initiation and incident event or study conclusion (406,030 thyroid hormone users with at least two free T4 measurements). Main Outcome Measures Incident atrial fibrillation and stroke. Results Overall, 71,333/643,687 (11.08%) participants developed incident atrial fibrillation and 41,931/663,809 (6.32%) stroke. In multivariable analyses controlling for pertinent factors such as age, sex and prior history of atrial fibrillation, low TSH or high free T4 levels (i.e., exogenous hyperthyroidism; e.g., TSH<0.1 mIU/L, OR 1.33, 95% CI 1.24-1.43) and high TSH or low free T4 levels (i.e., exogenous hypothyroidism; e.g., TSH>5.5 mIU/L, OR 1.29, 95% CI 1.26-1.33; free T4<0.7 ng/dL, OR 1.29, 95% CI 1.22-1.35) were associated with higher incidence of stroke compared to euthyroidism (TSH >0.5-5.5 mIU/L and free T4 0.7-1.9 ng/dL). Risk of developing atrial fibrillation and stroke was cumulative over time for both patients with exogenous hyperthyroidism and hypothyroidism. Conclusions Both exogenous hyper- and hypothyroidism were associated with increased risk of stroke, highlighting the importance of patient medication safety.

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The Association of Medications and Vaccination with Risk of Pneumonia in Inflammatory Bowel Disease

Inflammatory Bowel Diseases ◽

10.1093/ibd/izz189 ◽

2019 ◽

Vol 26 (6) ◽

pp. 919-925 ◽

Cited By ~ 4

Author(s):

Martin H Gregory ◽

Matthew A Ciorba ◽

Wyndy L Wiitala ◽

Ryan W Stidham ◽

Peter Higgins ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Pneumococcal Vaccination ◽

Population Based ◽

Tnf Inhibitors ◽

Veterans Health ◽

Health Administration ◽

Increased Risk ◽

Inflammatory Bowel ◽

The Impact

Abstract Background Patients with inflammatory bowel disease (IBD) are at increased risk for pneumonia, and corticosteroids are reported to amplify this risk. Less is known about the impact of corticosteroid-sparing IBD therapies on pneumonia risk or the efficacy of pneumococcal vaccination in reducing all-cause pneumonia in real-world IBD cohorts. Methods We performed a population-based study using an established Veterans Health Administration cohort of 29,957 IBD patients. We identified all patients who developed bacterial pneumonia. Cox survival analysis was used to determine the association of corticosteroids at study entry and as a time-varying covariate, corticosteroid-sparing agents (immunomodulators and antitumor necrosis-alpha [TNF] inhibitors), and pneumococcal vaccination with the development of all-cause pneumonia. Results Patients with IBD who received corticosteroids had a greater risk of pneumonia when controlling for age, gender, and comorbidities (hazard ratio [HR] 2.21; 95% confidence interval [CI], 1.90–2.57 for prior use; HR = 3.42; 95% CI, 2.92–4.01 for use during follow-up). Anti-TNF inhibitors (HR 1.52; 95% CI, 1.02–2.26), but not immunomodulators (HR 0.91; 95% CI, 0.77–1.07), were associated with a small increase in pneumonia. A history of pneumonia was strongly associated with subsequent pneumonia (HR = 4.41; 95% CI, 3.70–5.27). Less than 15% of patients were vaccinated against pneumococcus, and this was not associated with a reduced risk of pneumonia (HR = 1.02; 95% CI, 0.80–1.30) in this cohort. Conclusion In a large US cohort, corticosteroids were confirmed to increase pneumonia risk. Tumor necrosis-alpha inhibitors were associated with a smaller increase in the risk of pneumonia. Surprisingly, pneumococcal vaccination did not reduce all-cause pneumonia in this population, though few patients were vaccinated.

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Abstract MP23: Neighborhood Disadvantage And Oral Anticoagulant Use In Patients With Atrial Fibrillation

Circulation ◽

10.1161/circ.143.suppl_1.mp23 ◽

2021 ◽

Vol 143 (Suppl_1) ◽

Author(s):

Anne M McDermott ◽

Nadejda Kim ◽

Maria Mor ◽

MICHAEL J FINE ◽

Utibe Essien

Keyword(s):

Atrial Fibrillation ◽

Oral Anticoagulants ◽

Random Effect ◽

Adverse Outcomes ◽

System Level ◽

Veterans Health ◽

Health Administration ◽

Increased Risk ◽

Significant Difference ◽

The Impact

Background: Atrial Fibrillation (AF) is the most common heart rhythm disorder in the US and is treated with anticoagulation to mediate patients’ increased risk of ischemic stroke and death. Direct-acting oral anticoagulants (DOACs) are associated with better patient outcomes than warfarin, but prior studies show disparities in DOAC prescription. AF patients with low socioeconomic status (SES) have an increased risk of AF incidence, adverse outcomes, and mortality. Despite SES disparities in AF outcomes and prescribed medications, the impact of neighborhood SES (ADI) on AF management is unclear. We hypothesized that in comparison to patients with high ADI (e.g. the most disadvantaged), those with low ADI will be more likely to initiate any oral anticoagulants (OACs) and will be more likely to initiate DOACs. Methods: We conducted a retrospective observational study using national data from the Veterans Health Administration (VA) of newly diagnosed AF patients. Our independent variable was ADI, a marker of SES incorporating income, education, employment etc. Our model assessed numerous baseline patient, provider, and system-level covariates. We grouped patients into ADI quintiles, with Q1 being the lowest ADI (e.g., the least disadvantaged) and Q5 being the highest ADI, and used Q5 as a reference value. We used mixed effects logistic regression models, with site as a random effect, to determine the adjusted odds of initiating any OACs and of initiating DOACs by ADI quintile. Results: In our final cohort including 111,666 patients, 10,9386 (98.0%) were male and 2280 (2.0%) were female. The overall mean age at diagnosis was 72.86 (SD 10.4). Patients had the following medical comorbidities: Congestive heart failure: 18212, (16.3%); Hypertension: 84944, (76.1%); Diabetes: 70673, (63.3%); Vascular Disease: 46599, (41.7%). The ADI quintiles included the following patients: Q1: 21570, (20.3%); Q2: 21032, (19.8%); Q3: 21439, (20.2%); Q4: 20974, (19.8%); Q5: 21215, (20.0%). There was no significant difference in the odds of initiating any OAC between ADI quintiles compared to Q5 (Q1: adjusted odds ratio [95% CI], 0.95 [ 0.9, 1.01]; p=0.11). Among patients initiating DOAC, there was a significant association between low ADI and higher odds of initiating DOAC (Q1: 1.39 [1.29, 1.50]); (Q2: 1.18 [1.10, 1.27]); (Q3: 1.13 [1.06, 1.20]); (Q4: 1.09 [1.02, 1.16]). Each ADI quintile had a significantly higher odds of initiating DOACs compared to the highest ADI quintile. Conclusions: Patients with lower ADI are significantly more likely to be prescribed DOACs compared to patients with the highest levels of ADI. We found no significant difference in initiation of any OAC between ADI quintiles, which may result from high Warfarin utilization in the VA compared to the general population. Our data suggests that differences in neighborhood deprivation contribute to disparities in the prescribing DOACs in the VA.

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Opposing effects of thyroid hormones on cancer risk: a population-based study

Acta Endocrinologica ◽

10.1530/eje-20-1123 ◽

2021 ◽

Vol 184 (3) ◽

pp. 481-490

Author(s):

Eilon Krashin ◽

Barbara Silverman ◽

David M Steinberg ◽

Daniel Yekutieli ◽

Shmuel Giveon ◽

...

Keyword(s):

Thyroid Hormone ◽

Cancer Risk ◽

Thyroid Hormones ◽

Uterine Cancer ◽

Cox Proportional Hazards Model ◽

Prior History ◽

Cancer Type ◽

Free T4 ◽

Increased Risk ◽

Opposing Effects

Objective The association between dysregulated thyroid hormone function and cancer risk is inconclusive, especially among different age groups and uncommon malignancies. We sought to determine the relation of TSH and free T4 levels with overall cancer risk as well as risk of specific cancer types. Design and methods Data on thyroid hormone profile was collected from 375 635 Israeli patients with no prior history of cancer. Cancer cases were identified via the Israel National Cancer Registry. Cox proportional hazards model was used to assess hazard ratios for overall cancer as well as 20 cancer subgroups. Results In this study, 23 808 cases of cancer were detected over median follow up of 10.9 years. Among patients younger than 50 at inclusion, TSH in the hyperthyroid range, elevated free T4 and subclinical hyperthyroidism were associated with increased cancer risk (HR: 1.3, 1.28 and 1.31, respectively). In contrast, patients 50 or older with clinical hyperthyroidism were at lower cancer risk (HR: 0.64). Elevated TSH was associated with decreased risk of prostate cancer (HR: 0.67). Log-TSH elevation was associated with decreased risk of thyroid cancer (HR: 0.82) and increased risk of melanoma (HR: 1.11) and uterine cancer (HR: 1.27). Elevated free T4 was associated with increased lung cancer risk (HR: 1.54), while free T4 levels above the normal range and clinical hyperthyroidism were related to lower colorectal cancer risk (HR: 0.59 and 0.08, respectively). Conclusions Thyroid hormones display opposing effects on cancer risk, based on patient age and cancer type.

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Premature ventricular contraction is associated with increased risk of atrial fibrillation: a nationwide population-based study

Scientific Reports ◽

10.1038/s41598-021-81229-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yun Gi Kim ◽

Kyung-Do Han ◽

Jong-Il Choi ◽

Yun Young Choi ◽

Ha Young Choi ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Premature Ventricular Contraction ◽

Population Based ◽

Prior History ◽

Ventricular Contraction ◽

Increased Risk ◽

History Of ◽

Atrial Ectopy ◽

New Onset

AbstractPremature ventricular contraction (PVC) and atrial fibrillation (AF) are common arrhythmias affecting 1–2% of the general population. During PVC, retrograde ventriculo-atrial activation can occur and act like an atrial ectopy. However, the clinical significance of this phenomenon is not fully understood. We aimed to elucidate whether the clinical diagnosis of PVC can increase the risk of new-onset AF. We performed a nationwide population-based analysis using the Korean National Health Insurance Service database. A total of 9,537,713 people without prior history of PVC and AF were identified. Among these people, 4135 developed PVC in 2009, and people with and without PVC were followed until 2018. People who had PVC showed an increased risk of new-onset AF as compared with people without PVC (hazard ratio [HR] = 2.705; 95% confidence interval [CI] = 2.428–3.013; p < 0.001). The risk of ischemic stroke was also significantly increased in people with PVC (HR 1.160; 95% CI 1.048–1.284; p = 0.0041). New-onset AF developed in 72 people (19.3%) among 374 people with PVC who had ischemic stroke during their follow-up. A significant interaction was observed between PVC and age with people < 65 years at greater risk of new-onset AF for having PVC. In this observational analysis, the risk of new-onset AF and ischemic stroke was increased in people with PVC. Additional evaluation to identify AF in people with PVC can be helpful.

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Associations between stopping prescriptions for opioids, length of opioid treatment, and overdose or suicide deaths in US veterans: observational evaluation

BMJ ◽

10.1136/bmj.m283 ◽

2020 ◽

pp. m283 ◽

Cited By ~ 12

Author(s):

Elizabeth M Oliva ◽

Thomas Bowe ◽

Ajay Manhapra ◽

Stefan Kertesz ◽

Jennifer M Hah ◽

...

Keyword(s):

Opioid Analgesic ◽

Veterans Health Administration ◽

Fiscal Year ◽

Veterans Health ◽

Health Administration ◽

Opioid Treatment ◽

Risk Of Death ◽

Length Of Treatment ◽

Increased Risk ◽

Stopping Treatment

Abstract Objective To examine the associations between stopping treatment with opioids, length of treatment, and death from overdose or suicide in the Veterans Health Administration. Design Observational evaluation. Setting Veterans Health Administration. Participants 1 394 102 patients in the Veterans Health Administration with an outpatient prescription for an opioid analgesic from fiscal year 2013 to the end of fiscal year 2014 (1 October 2012 to 30 September 2014). Main outcome measures A multivariable Cox non-proportional hazards regression model examined death from overdose or suicide, with the interaction of time varying opioid cessation by length of treatment (≤30, 31-90, 91-400, and >400 days) as the main covariates. Stopping treatment with opioids was measured as the time when a patient was estimated to have no prescription for opioids, up to the end of the next fiscal year (2014) or the patient’s death. Results 2887 deaths from overdose or suicide were found. The incidence of stopping opioid treatment was 57.4% (n = 799 668) overall, and based on length of opioid treatment was 32.0% (≤30 days), 8.7% (31-90 days), 22.7% (91-400 days), and 36.6% (>400 days). The interaction between stopping treatment with opioids and length of treatment was significant (P<0.001); stopping treatment was associated with an increased risk of death from overdose or suicide regardless of the length of treatment, with the risk increasing the longer patients were treated. Hazard ratios for patients who stopped opioid treatment (with reference values for all other covariates) were 1.67 (≤30 days), 2.80 (31-90 days), 3.95 (91-400 days), and 6.77 (>400 days). Descriptive life table data suggested that death rates for overdose or suicide increased immediately after starting or stopping treatment with opioids, with the incidence decreasing over about three to 12 months. Conclusions Patients were at greater risk of death from overdose or suicide after stopping opioid treatment, with an increase in the risk the longer patients had been treated before stopping. Descriptive data suggested that starting treatment with opioids was also a risk period. Strategies to mitigate the risk in these periods are not currently a focus of guidelines for long term use of opioids. The associations observed cannot be assumed to be causal; the context in which opioid prescriptions were started and stopped might contribute to risk and was not investigated. Safer prescribing of opioids should take a broader view on patient safety and mitigate the risk from the patient’s perspective. Factors to address are those that place patients at risk for overdose or suicide after beginning and stopping opioid treatment, especially in the first three months.

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Non-invasive mid-term ECG monitoring for the detection of atrial fibrillation in an outpatient population

European Heart Journal ◽

10.1093/ehjci/ehaa946.0381 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

J Cai ◽

K.K Yeo ◽

P Wong ◽

C.K Ching

Keyword(s):

Atrial Fibrillation ◽

Public Institution ◽

First Episode ◽

Prior History ◽

Funding Source ◽

Monitoring Device ◽

Ecg Monitoring ◽

Non Invasive ◽

Increased Risk ◽

The Mean

Abstract Background Atrial fibrillation (AF) is a common arrhythmia with significant morbidity due to an increased risk of ischemic stroke. Outpatient electrocardiogram (ECG) monitoring is an integral part of the diagnosis of AF. Conventional 24 hour Holter monitoring can be cumbersome and often fails to diagnose patients with paroxysmal AF. Spyder ECG is a non-invasive ECG monitoring device that allows wireless transmission of ECG information for analysis. It is small and comfortable, allowing for easy application for the screening and detection of AF over a mid-term duration. Purpose This study aims to evaluate the incidence of AF in patients with no prior AF and CHADsVASC score of at least 1 with the use of the Spyder ECG mid-term ECG monitoring device. Methods Patients aged 21 to 85 years old with no prior history of AF and CHADsVASC score of at least 1 were recruited from outpatient clinics of 3 large tertiary hospitals in Singapore from December 2016 to April 2019. Patients wore the Spyder ECG device for up to 2 weeks, during which continuous ECG information was uploaded onto a central cloud database and analysed. Results There were 363 patients recruited. The mean age was 61±10.0 years and 65.1% were male. There were 80.3% Chinese, 11.6% Malay, 7.5% Indian and 20.6% of other races. 68.3% of the patients were non-smokers and 74.0% of them were non-alcohol drinkers. The mean BMI of 25.5±4.7 kg/m2. The patient population had significant co-morbidities. 76.3% of the patients had hypertension, 69.4% of them had hyperlipidemia and 40.5% of them had diabetes mellitus. 10.0% of them had congestive cardiac failure and 56.7% had ischaemic heart disease. 11.3% of patients had a previous stroke and 20.4% had a prior myocardial infarction. 7.8% of the patients had asthma, 5.8% of them had thyroid disease and 9.9% of them had chronic kidney disease. They were monitored for a mean of 5.4±2.9 days each. There were 15 (4.1%) patients in whom AF was detected. The patients with AF wore the device for a mean of 5.7±2.0 SD days. The mean burden of AF was 9.0% of monitored time. 46.7% of the patients with AF had detection of AF on the first day, 26.7% on the second day, 13.3% on the third day and 13.3% on the seventh day. The mean duration of the first episode of AF was 251±325 minutes. 7 out of 15 (46.7%) of patients had first episodes of AF lasting less than 10 minutes. Conclusion Continuous mid-term ECG monitoring was able to detect AF in 15 (4.1%) of a population of 363 patients with no prior AF and CHADsVASC score of at least one, monitored for a mean of 5.4 days. Most episodes (53.3%) of AF were detected after the first day of ECG monitoring. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Duke-NUS Medical School Singapore

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Abstract 14: The Influence of Provider Specialty on Anticoagulation Prescription Fills and Stroke Risk in Atrial Fibrillation Patients With History of Cancer

Circulation Cardiovascular Quality and Outcomes ◽

10.1161/circoutcomes.11.suppl_1.14 ◽

2018 ◽

Vol 11 (suppl_1) ◽

Author(s):

Wesley T O’Neal ◽

J’Neka Claxton ◽

Richard MacLehose ◽

Lin Chen ◽

Lindsay G Bengtson ◽

...

Keyword(s):

Atrial Fibrillation ◽

Oral Anticoagulant ◽

Cox Regression ◽

Prior History ◽

Cancer Type ◽

Patients With Cancer ◽

Increased Risk ◽

History Of ◽

Reduced Risk ◽

History Of Cancer

Background: Early cardiology involvement within 90 days of atrial fibrillation (AF) diagnosis is associated with greater likelihood of oral anticoagulant use and a reduced risk of stroke. Due to variation in cardiovascular care for patients with cancer, it is possible that a similar association does not exist for AF patients with cancer. Methods: We examined the association of early cardiology involvement with oral anticoagulation use among non-valvular AF patients with history of cancer (past or active), using data from 388,045 patients (mean age=68±15 years; 59% male) from the MarketScan database (2009-2014). ICD-9 codes in any position were used to identify cancer diagnosis prior to AF diagnosis. Provider specialty and filled anticoagulant prescriptions 3 months prior to and 6 months after AF diagnosis were obtained. Poisson regression models were used to compute the probability of an oral anticoagulant prescription fill and Cox regression was used to estimate the risk of stroke and major bleeding. Results: A total of 64,016 (17%) AF patients had a prior history of cancer. Cardiology involvement was less likely to occur among patients with history of cancer than those without (relative risk=0.92, 95% confidence interval (0.91, 0.93)). Similar differences were observed for cancers of the colon (0.90 (0.88, 0.92)), lung (0.76 (0.74, 0.78)), pancreas (0.74 (0.69, 0.80)), and hematologic system (0.88 (0.87, 0.90)), while no differences were observed for breast or prostate cancers. Patients with cancer were less likely to fill prescriptions for anticoagulants (0.89 (0.88, 0.90)) than those without cancer, and similar results were observed for cancers of the colon, lung, prostate, pancreas, and hematologic system. However, patients with cancer were more likely to fill prescriptions for anticoagulants (1.48 (1.45, 1.52)) if seen by a cardiology provider, regardless of cancer type. A reduced risk of stroke (hazard ratio=0.89 (0.81, 0.99)) was observed among all cancer patients who were seen by a cardiology provider than among those who were not, without an increased risk of bleeding (1.04 (0.95, 1.13)). Conclusion: AF patients with cancer were less likely to see a cardiologist, and less likely to fill an anticoagulant prescription than AF patients without cancer. However, cardiology involvement was associated with increased anticoagulant prescription fills and reduced risk of stroke, suggesting a beneficial role for cardiology providers to improve outcomes in AF patients with history of cancer.

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Association between acute psychiatric bed availability in the Veterans Health Administration and veteran suicide risk: a retrospective cohort study

BMJ Quality & Safety ◽

10.1136/bmjqs-2020-012975 ◽

2021 ◽

pp. bmjqs-2020-012975

Author(s):

Peter J Kaboli ◽

Matthew R Augustine ◽

Bjarni Haraldsson ◽

Nicholas M Mohr ◽

M Bryant Howren ◽

...

Keyword(s):

Mental Health ◽

Cohort Study ◽

Retrospective Cohort Study ◽

Retrospective Cohort ◽

Suicide Risk ◽

Veterans Health Administration ◽

Veterans Health ◽

Health Administration ◽

Bed Occupancy ◽

Increased Risk

BackgroundVeteran suicides have increased despite mental health investments by the Veterans Health Administration (VHA).ObjectiveTo examine relationships between suicide and acute inpatient psychiatric bed occupancy and other community, hospital and patient factors.MethodsRetrospective cohort study using administrative and publicly available data for contextual community factors. The study sample included all veterans enrolled in VHA primary care in 2011–2016 associated with 111 VHA hospitals with acute inpatient psychiatric units. Acute psychiatric bed occupancy, as a measure of access to care, was the main exposure of interest and was categorised by quarter as per cent occupied using thresholds of ≤85%, 85.1%–90%, 90.1%–95% and >95%. Hospital-level analyses were conducted using generalised linear mixed models with random intercepts for hospital, modelling number of suicides by quarter with a negative binomial distribution.ResultsFrom 2011 to 2016, the national incidence of suicide among enrolled veterans increased from 39.7 to 41.6 per 100 000 person-years. VHA psychiatric bed occupancy decreased from a mean of 68.2% (IQR 56.5%–82.2%) to 65.4% (IQR 53.9%–79.9%). VHA hospitals with the highest occupancy (>95%) in a quarter compared with ≤85% had an adjusted incident rate ratio (IRR) for suicide of 1.10 (95% CI 1.01 to 1.19); no increased risk was observed for 85.1%–90% (IRR 0.96; 95% CI 0.89 to 1.03) or 90.1%–95% (IRR 0.96; 95% CI 0.89 to 1.04) compared with ≤85% occupancy. Of hospital and community variables, suicide risk was not associated with number of VHA or non-VHA psychiatric beds or amount spent on community mental health. Suicide risk increased by age categories, seasons, geographic regions and over time.ConclusionsHigh VHA hospital occupancy (>95%) was associated with a 10% increased suicide risk for veterans whereas absolute number of beds was not, suggesting occupancy is an important access measure. Future work should clarify optimal bed occupancy to meet acute psychiatric needs and ensure adequate bed distribution.

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Enhancing Regulatory Decision Making for Postmarket Drug Safety

Management Science ◽

10.1287/mnsc.2020.3889 ◽

2021 ◽

Author(s):

Vishal Ahuja ◽

Carlos A. Alvarez ◽

John R. Birge ◽

Chad Syverson

Keyword(s):

Decision Making ◽

Operations Management ◽

The United States ◽

Pharmaceutical Products ◽

Unintended Consequences ◽

Surveillance Systems ◽

Veterans Health ◽

Health Administration ◽

Regulatory Decision ◽

Increased Risk

The U.S. Food and Drug Administration (FDA) regulates the approval and safe public use of pharmaceutical products in the United States. The FDA uses postmarket surveillance systems to monitor drugs already on the market; a drug found to be associated with an increased risk of adverse events (ADEs) is subject to a recall or a warning. A flawed postmarket decision-making process can have unintended consequences for patients, create uncertainty among providers and affect their prescribing practices, and subject the FDA to unfavorable public scrutiny. The FDA’s current pharmacovigilance process suffers from several shortcomings (e.g., a high underreporting rate), often resulting in incorrect or untimely decisions. Thus, there is a need for robust, data-driven approaches to support and enhance regulatory decision making in the context of postmarket pharmacovigilance. We propose such an approach that has several appealing features—it employs large, reliable, and relevant longitudinal databases; it uses methods firmly established in literature; and it addresses selection bias and endogeneity concerns. Our approach can be used to both (i) independently validate existing safety concerns relating to a drug, such as those emanating from existing surveillance systems, and (ii) perform a holistic safety assessment by evaluating a drug’s association with other ADEs to which the users may be susceptible. We illustrate the utility of our approach by applying it retrospectively to a highly publicized FDA black box warning (BBW) for rosiglitazone, a diabetes drug. Using comprehensive data from the Veterans Health Administration on more than 320,000 diabetes patients over an eight-year period, we find that the drug was not associated with the two ADEs that led to the BBW, a conclusion that the FDA evidently reached, as it retracted the warning six years after issuing it. We demonstrate the generalizability of our approach by retroactively evaluating two additional warnings, those related to statins and atenolol, which we found to be valid. This paper was accepted by Vishal Gaur, operations management.

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Abstract 12385: Past Alcohol Consumption and Incident Atrial Fibrillation

Circulation ◽

10.1161/circ.132.suppl_3.12385 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Shalini Dixit ◽

Alvaro Alonso ◽

Elsayed Z Soliman ◽

Lin Y Chen ◽

Gregory M Marcus

Keyword(s):

Atrial Fibrillation ◽

Alcohol Consumption ◽

Alcohol Use ◽

Population Based ◽

Self Report ◽

Atherosclerosis Risk In Communities ◽

Increased Risk ◽

Before And After ◽

Dietary Intake Assessment ◽

Aric Study

Introduction: Although current alcohol consumption appears to be a risk factor for incident atrial fibrillation (AF), limitations related to self-reported alcohol use and confounding in observational studies limit the certainty of conclusions regarding causality. Whether cessation of alcohol consumption can protect against incident AF remains unknown. Methods: We examined all participants in the Atherosclerosis Risk in Communities (ARIC) study, a population-based cohort of 15,792 men and women aged 45-65, without prevalent AF. Past alcohol consumption was assessed via self-report during the baseline dietary intake assessment. Cases of incident AF were ascertained via study ECGs, hospital discharge ICD-9 codes, and death certificates. Results: Among 15,262 participants with complete survey data, 2,898 (19.0%) were former drinkers. During an average follow-up of 17.4 years, there were 380 cases of incident AF in former consumers. Both before and after adjustment for potential confounders, a longer duration of alcohol abstinence was associated with a lower risk of developing AF; previously consuming alcohol for a longer duration and consuming a greater quantity of alcohol were each associated with a higher risk of developing AF (Table). Conclusions: Among former drinkers, the number of years of drinking and the amount of alcohol consumed may each confer an increased risk of AF. Given that a longer duration of abstinence was associated with a decreased risk of AF, modification of alcohol use could potentially play a role in AF prevention.

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