Daniel S. Budnitz

Emergency Hospitalizations for Adverse Drug Events in Older Americans

BACKGROUND Adverse drug events are important preventable causes of hospitalization in older adults. However, nationally representative data on adverse drug events that result in hospitalization in this population have been limited. METHODS We used adverse-event data from the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance project (2007 through 2009) to estimate the frequency and rates of hospitalization after emergency department visits for adverse drug events in older adults and to assess the contribution of specific medications, including those identified as high-risk or potentially inappropriate by national quality measures. RESULTS On the basis of 5077 cases identified in our sample, there were an estimated 99,628 emergency hospitalizations (95% confidence interval [CI], 55,531 to 143,724) for adverse drug events in U.S. adults 65 years of age or older each year from 2007 through 2009. Nearly half of these hospitalizations were among adults 80 years of age or older (48.1%; 95% CI, 44.6 to 51.6). Nearly two thirds of hospitalizations were due to unintentional overdoses (65.7%; 95% CI, 60.1 to 71.3). Four medications or medication classes were implicated alone or in combination in 67.0% (95% CI, 60.0 to 74.1) of hospitalizations: warfarin (33.3%), insulins (13.9%), oral antiplatelet agents (13.3%), and oral hypoglycemic agents (10.7%). High-risk medications were implicated in only 1.2% (95% CI, 0.7 to 1.7) of hospitalizations. CONCLUSIONS Most emergency hospitalizations for recognized adverse drug events in older adults resulted from a few commonly used medications, and relatively few resulted from medications typically designated as high-risk or inappropriate. Improved management of antithrombotic and antidiabetic drugs has the potential to reduce hospitalizations for adverse drug events in older adults.

Medication Use Leading to Emergency Department Visits for Adverse Drug Events in Older Adults

Context Emergency department visits by older adults are often due to adverse drug events, but the proportion of these visits that are the result of drugs designated as inappropriate for use in this population is unknown. Contribution Analyses of a national surveillance study of adverse drug events and a national outpatient survey estimate that Americans age 65 years or older have more than 175000 emergency department visits for adverse drug events yearly. Three commonly prescribed drugs accounted for more than one third of visits: warfarin, insulin, and digoxin. Caution The study was limited to adverse events in the emergency department. Implication Strategies to decrease adverse drug events among older adults should focus on warfarin, insulin, and digoxin. The Editors Adverse drug events cause clinically significant morbidity and mortality and are associated with large economic costs (15). They are common in older adults, regardless of whether they live in the community, reside in long-term care facilities, or are hospitalized (59). Most physicians recognize that prescribing medications to older patients requires special considerations, but nongeriatricians are typically unfamiliar with the most commonly used measure of medication appropriateness for older patients: the Beers criteria (1012). The Beers criteria are a consensus-based list of medications identified as potentially inappropriate for use in older adults. The criteria were introduced in 1991 to help researchers evaluate prescription quality in nursing homes (10). The Beers criteria were updated in 1997 and 2003 to apply to all persons age 65 years or older, to include new medications judged to be ineffective or to pose unnecessarily high risk, and to rate the severity of adverse outcomes (11, 12). Prescription rates of Beers criteria medications have become a widely used measure of quality of care for older adults in research studies in the United States and elsewhere (1326). The application of the Beers criteria as a measure of health care quality and safety has expanded beyond research studies. The Centers for Medicare & Medicaid Services incorporated the Beers criteria into federal safety regulations for long-term care facilities in 1999 (27). The prescription rate of potentially inappropriate medications is one of the few medication safety measures in the National Healthcare Quality Report (28) and has been introduced as a Health Plan and Employer Data and Information Set quality measure for managed care plans (29). Despite widespread adoption of the Beers criteria to measure prescription quality and safety, as well as proposals to apply these measures to additional settings, such as medication therapy management services under Medicare Part D (30), population-based data on the effect of adverse events from potentially inappropriate medications are sparse and do not compare the risks for adverse events from Beers criteria medications against those from other medications (31, 32). Adverse drug events that lead to emergency department visits are clinically significant adverse events (5) and result in increased health care resource utilization and expense (6). We used nationally representative public health surveillance data to estimate the number of emergency department visits for adverse drug events involving Beers criteria medications and compared the number with that for adverse drug events involving other medications. We also estimated the frequency of outpatient prescription of Beers criteria medications and other medications to calculate and compare the risks for emergency department visits for adverse drug events per outpatient prescription visit. Methods Data Sources National estimates of emergency department visits for adverse drug events were based on data from the 58 nonpediatric hospitals participating in the National Electronic Injury Surveillance SystemCooperative Adverse Drug Event Surveillance (NEISS-CADES) System, a nationally representative, size-stratified probability sample of hospitals (excluding psychiatric and penal institutions) in the United States and its territories with a minimum of 6 beds and a 24-hour emergency department (Figure 1) (3335). As described elsewhere (5, 34), trained coders at each hospital reviewed clinical records of every emergency department visit to report physician-diagnosed adverse drug events. Coders reported clinical diagnosis, medication implicated in the adverse event, and narrative descriptions of preceding circumstances. Data collection, management, quality assurance, and analyses were determined to be public health surveillance activities by the Centers for Disease Control and Prevention (CDC) and U.S. Food and Drug Administration human subjects oversight bodies and, therefore, did not require human subject review or institutional review board approval. Figure 1. Data sources and descriptions. NAMCS= National Ambulatory Medical Care Survey (36); NEISS-CADES= National Electronic Injury Surveillance SystemCooperative Adverse Drug Event Surveillance System (5, 3335); NHAMCS = National Hospital Ambulatory Medical Care Survey (37). *The NEISS-CADES is a 63-hospital national probability sample, but 5 pediatric hospitals were not included in this analysis. National estimates of outpatient prescription were based on 2 cross-sectional surveys, the National Ambulatory Medical Care Survey (NAMCS) and the National Hospital Ambulatory Medical Care Survey (NHAMCS), designed to provide information on outpatient office visits and visits to hospital outpatient clinics and emergency departments (Figure 1) (36, 37). These surveys have been previously used to document the prescription rates of inappropriate medications (17, 3840). Definition of Potentially Inappropriate Medications The most recent iteration of the Beers criteria (12) categorizes 41 medications or medication classes as potentially inappropriate under any circumstances (always potentially inappropriate) and 7 medications or medication classes as potentially inappropriate when used in certain doses, frequencies, or durations (potentially inappropriate in certain circumstances). For example, ferrous sulfate is considered to be potentially inappropriate only when used at dosages greater than 325 mg/d, but not potentially inappropriate if used at lower dosages. For this investigation, we included the Beers criteria medications listed in Table 1. Because medication dose, duration, and frequency were not always available in NEISS-CADES and are not reported in NAMCS and NHAMCS, we included medications regardless of dose, duration, or frequency of use. We excluded 3 medications considered to be potentially inappropriate when used in specific formulations (short-acting nifedipine, short-acting oxybutynin, and desiccated thyroid) because NEISS-CADES, NAMCS, and NHAMCS do not reliably identify these formulations. Table 1. Potentially Inappropriate Medications for Individuals Age 65 Years or Older The updated Beers criteria identify additional medications as potentially inappropriate if they are prescribed to patients who have certain preexisting conditions. We did not include these medications because they have rarely been used in previous studies or safety measures and NEISS-CADES, NAMCS, and NHAMCS do not reliably identify preexisting conditions. Identification of Emergency Department Visits for Adverse Drug Events We defined an adverse drug event case as an incident emergency department visit by a patient age 65 years or older, from 1 January 2004 to 31 December 2005, for a condition that the treating physician explicitly attributed to the use of a drug or for a drug-specific effect (5). Adverse events include allergic reactions (immunologically mediated effects) (41), adverse effects (undesirable pharmacologic or idiosyncratic effects at recommended doses) (41), unintentional overdoses (toxic effects linked to excess dose or impaired excretion) (41), or secondary effects (such as falls and choking). We excluded cases of intentional self-harm, therapeutic failures, therapy withdrawal, drug abuse, adverse drug events that occurred as a result of medical treatment received during the emergency department visit, and follow-up visits for a previously diagnosed adverse drug event. We defined an adverse drug event from Beers criteria medications as an emergency department visit in which a medication from Table 1 was implicated. Identification of Outpatient Prescription Visits We used the NAMCS and NHAMCS public use data files for the most recent year available (2004) to identify outpatient prescription visits. We defined an outpatient prescription visit as any outpatient office, hospital clinic, or emergency department visit at which treatment with a medication of interest was either started or continued. We identified medications by generic name for those with a single active ingredient and by individual active ingredients for combination products. We categorized visits with at least 1 medication identified in Table 1 as involving Beers criteria medications. Statistical Analysis Each NEISS-CADES, NAMCS, and NHAMCS case is assigned a sample weight on the basis of the inverse probability of selection (33, 4244). We calculated national estimates of emergency department visits and prescription visits by summing the corresponding sample weights, and we calculated 95% CIs by using the SURVEYMEANS procedure in SAS, version 9.1 (SAS Institute, Cary, North Carolina), to account for the sampling strata and clustering by site. To obtain annual estimates of visits for adverse events, we divided NEISS-CADES estimates for 20042005 and corresponding 95% CI end points by 2. Estimates based on small numbers of cases (<20 cases for NEISS-CADES and <30 cases for NAMCS and NHAMCS) or with a coefficient of variation greater than 30% are considered statistically unstable and are identified in the tables. To estimate the risk for adverse events relative to outpatient prescription

Emergency Department Visits for Antibiotic- Associated Adverse Events

BACKGROUND Drug-related adverse events are an under-appreciated consequence of antibiotic use, and the national magnitude and scope of these events have not been studied. Our objective was to estimate and compare the numbers and rates of emergency department (ED) visits for drug-related adverse events associated with systemic antibiotics in the United States by drug class, individual drug, and event type. METHODS We analyzed drug-related adverse events from the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance project (2004-2006) and outpatient prescriptions from national sample surveys of ambulatory care practices, the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey (2004-2005). RESULTS On the basis of 6614 cases, an estimated 142,505 visits (95% confidence interval [CI], 116,506-168,504 visits) annually were made to US EDs for drug-related adverse events attributable to systemic antibiotics. Antibiotics were implicated in 19.3% of all ED visits for drug-related adverse events. Most ED visits for antibiotic-associated adverse events were for allergic reactions (78.7% of visits; 95% CI, 75.3%-82.1% of visits). One-half of the estimated ED visits were attributable to penicillins (36.9% of visits; 95% CI, 34.7%-39.2% of visits) and cephalosporins (12.2%; 95% CI, 10.9%-13.5%). Among commonly prescribed antibiotics, sulfonamides and clindamycin were associated with the highest rate of ED visits (18.9 ED visits per 10,000 outpatient prescription visits [95% CI, 13.1-24.7 ED visits per 10,000 outpatient prescription visits] and 18.5 ED visits per 10,000 outpatient prescription visits [95% CI, 12.1-25.0 ED visits per 10,000 outpatient prescription visits], respectively). Compared with all other antibiotic classes, sulfonamides were associated with a significantly higher rate of moderate-to-severe allergic reactions (4.3% [95% CI, 2.9%-5.8%] vs. 1.9 % [95% CI, 1.5%-2.3%]), and sulfonamides and fluoroquinolones were associated with a significantly higher rate of neurologic or psychiatric disturbances (1.4% [95% CI, 1.0%-1.7%] vs. 0.5% [95% CI, 0.4%-0.6%]). CONCLUSIONS Antibiotic-associated adverse events lead to many ED visits, and allergic reactions are the most common events. Minimizing unnecessary antibiotic use by even a small percentage could significantly reduce the immediate and direct risks of drug-related adverse events in individual patients.

Emergency Department Visits for Adverse Events Related to Dietary Supplements

BACKGROUND Dietary supplements, such as herbal or complementary nutritional products and micronutrients (vitamins and minerals), are commonly used in the United States, yet national data on adverse effects are limited. METHODS We used nationally representative surveillance data from 63 emergency departments obtained from 2004 through 2013 to describe visits to U.S. emergency departments because of adverse events related to dietary supplements. RESULTS On the basis of 3667 cases, we estimated that 23,005 (95% confidence interval [CI], 18,611 to 27,398) emergency department visits per year were attributed to adverse events related to dietary supplements. These visits resulted in an estimated 2154 hospitalizations (95% CI, 1342 to 2967) annually. Such visits frequently involved young adults between the ages of 20 and 34 years (28.0% of visits; 95% CI, 25.1 to 30.8) and unsupervised children (21.2% of visits; 95% CI, 18.4 to 24.0). After the exclusion of unsupervised ingestion of dietary supplements by children, 65.9% (95% CI, 63.2 to 68.5) of emergency department visits for single-supplement-related adverse events involved herbal or complementary nutritional products; 31.8% (95% CI, 29.2 to 34.3) involved micronutrients. Herbal or complementary nutritional products for weight loss (25.5%; 95% CI, 23.1 to 27.9) and increased energy (10.0%; 95% CI, 8.0 to 11.9) were commonly implicated. Weight-loss or energy products caused 71.8% (95% CI, 67.6 to 76.1) of supplement-related adverse events involving palpitations, chest pain, or tachycardia, and 58.0% (95% CI, 52.2 to 63.7) involved persons 20 to 34 years of age. Among adults 65 years of age or older, choking or pill-induced dysphagia or globus caused 37.6% (95% CI, 29.1 to 46.2) of all emergency department visits for supplement-related adverse events; micronutrients were implicated in 83.1% (95% CI, 73.3 to 92.9) of these visits. CONCLUSIONS An estimated 23,000 emergency department visits in the United States every year are attributed to adverse events related to dietary supplements. Such visits commonly involve cardiovascular manifestations from weight-loss or energy products among young adults and swallowing problems, often associated with micronutrients, among older adults. (Funded by the Department of Health and Human Services.).

National Estimates of Insulin-related Hypoglycemia and Errors Leading to Emergency Department Visits and Hospitalizations

IMPORTANCE Detailed, nationally representative data describing high-risk populations and circumstances involved in insulin-related hypoglycemia and errors (IHEs) can inform approaches to individualizing glycemic targets. OBJECTIVE To describe the US burden, rates, and characteristics of emergency department (ED) visits and emergency hospitalizations for IHEs. DESIGN, SETTING, AND PARTICIPANTS Nationally representative public health surveillance of adverse drug events among insulin-treated patients seeking ED care (National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance project) and a national household survey of insulin use (the National Health Interview Survey) were used to obtain data from January 1, 2007, through December 31, 2011. MAIN OUTCOMES AND MEASURES Estimated annual numbers and estimated annual rates of ED visits and hospitalizations for IHEs among insulin-treated patients with diabetes mellitus. RESULTS Based on 8100 National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance cases, an estimated 97,648 (95% CI, 64,410-130,887) ED visits for IHEs occurred annually; almost one-third (29.3%; 95% CI, 21.8%-36.8%) resulted in hospitalization. Severe neurologic sequelae were documented in an estimated 60.6% (95% CI, 51.3%-69.9%) of ED visits for IHEs, and blood glucose levels of 50 mg/dL (to convert to millimoles per liter, multiply by 0.0555) or less were recorded in more than half of cases (53.4%). Insulin-treated patients 80 years or older were more than twice as likely to visit the ED (rate ratio, 2.5; 95% CI, 1.5-4.3) and nearly 5 times as likely to be subsequently hospitalized (rate ratio, 4.9; 95% CI, 2.6-9.1) for IHEs than those 45 to 64 years. The most commonly identified IHE precipitants were reduced food intake and administration of the wrong insulin product. CONCLUSIONS AND RELEVANCE Rates of ED visits and subsequent hospitalizations for IHEs were highest in patients 80 years or older; the risks of hypoglycemic sequelae in this age group should be considered in decisions to prescribe and intensify insulin. Meal-planning misadventures and insulin product mix-ups are important targets for hypoglycemia prevention efforts.

Medication overdoses leading to emergency department visits among children

BACKGROUND The high prevalence of medication use increases the potential for medication overdoses, especially among children. PURPOSE This paper describes the burden of unintentional pediatric medication overdoses in order to target new prevention efforts. METHODS Data were analyzed in 2007 and 2008 from the National Electronic Injury Surveillance System, collected January 1, 2004, through December 31, 2005, to estimate the number of emergency department visits resulting from unintentional medication overdoses among children aged <or=18 years in the U.S. These data were analyzed by patient demographics, overdose cause, and implicated products, and compared to visits for nonpharmaceutical consumer product poisonings. RESULTS Based on 3034 cases, an estimated 71,224 emergency department visits for medication overdoses were made annually by children aged <or=18 years, representing 68.9% of emergency department visits for unintentional pediatric poisonings. The rate of unintentional poisonings from medications was twice the rate of those from nonpharmaceutical consumer products (9.2 visits per 10,000 individuals per year [95% CI=7.3, 11.0] vs 4.2 per 10,000 individuals per year [95% CI=3.3, 5.0]). Four fifths (82.2%) of visits for medication overdoses were from unsupervised ingestions (children accessing medications on their own); medication errors and misuse resulted in 14.3% of visits. Most visits (81.3%) involved children aged <or=5 years, and commonly available over-the-counter medications were implicated in one third (33.9%) of visits. CONCLUSIONS Medication overdoses among children, notably unsupervised ingestions, represent a substantial burden in terms of emergency department visits and hospitalizations. New efforts to prevent pediatric medication overdoses are needed.

US Emergency Department Visits for Outpatient Adverse Drug Events, 2013-2014

Importance The Patient Protection and Affordable Care Act of 2010 brought attention to adverse drug events in national patient safety efforts. Updated, detailed, nationally representative data describing adverse drug events can help focus these efforts. Objective To describe the characteristics of emergency department (ED) visits for adverse drug events in the United States in 2013-2014 and describe changes in ED visits for adverse drug events since 2005-2006. Design, Setting, and Participants Active, nationally representative, public health surveillance in 58 EDs located in the United States and participating in the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance project. Exposures Drugs implicated in ED visits. Main Outcomes and Measures National weighted estimates of ED visits and subsequent hospitalizations for adverse drug events. Results Based on data from 42 585 cases, an estimated 4.0 (95% CI, 3.1-5.0) ED visits for adverse drug events occurred per 1000 individuals annually in 2013 and 2014 and 27.3% (95% CI, 22.2%-32.4%) of ED visits for adverse drug events resulted in hospitalization. An estimated 34.5% (95% CI, 30.3%-38.8%) of ED visits for adverse drug events occurred among adults aged 65 years or older in 2013-2014 compared with an estimated 25.6% (95% CI, 21.1%-30.0%) in 2005-2006; older adults experienced the highest hospitalization rates (43.6%; 95% CI, 36.6%-50.5%). Anticoagulants, antibiotics, and diabetes agents were implicated in an estimated 46.9% (95% CI, 44.2%-49.7%) of ED visits for adverse drug events, which included clinically significant adverse events, such as hemorrhage (anticoagulants), moderate to severe allergic reactions (antibiotics), and hypoglycemia with moderate to severe neurological effects (diabetes agents). Since 2005-2006, the proportions of ED visits for adverse drug events from anticoagulants and diabetes agents have increased, whereas the proportion from antibiotics has decreased. Among children aged 5 years or younger, antibiotics were the most common drug class implicated (56.4%; 95% CI, 51.8%-61.0%). Among children and adolescents aged 6 to 19 years, antibiotics also were the most common drug class implicated (31.8%; 95% CI, 28.7%-34.9%) in ED visits for adverse drug events, followed by antipsychotics (4.5%; 95% CI, 3.3%-5.6%). Among older adults (aged ≥65 years), 3 drug classes (anticoagulants, diabetes agents, and opioid analgesics) were implicated in an estimated 59.9% (95% CI, 56.8%-62.9%) of ED visits for adverse drug events; 4 anticoagulants (warfarin, rivaroxaban, dabigatran, and enoxaparin) and 5 diabetes agents (insulin and 4 oral agents) were among the 15 most common drugs implicated. Medications to always avoid in older adults according to Beers criteria were implicated in 1.8% (95% CI, 1.5%-2.1%) of ED visits for adverse drug events. Conclusions and Relevance The prevalence of emergency department visits for adverse drug events in the United States was estimated to be 4 per 1000 individuals in 2013 and 2014. The most common drug classes implicated were anticoagulants, antibiotics, diabetes agents, and opioid analgesics.

Adverse Events From Cough and Cold Medications in Children

BACKGROUND. Adverse drug events in children from cough and cold medications have been identified as a public health issue with clinical and policy implications. Nationally representative morbidity data could be useful for targeting age-appropriate safety interventions. OBJECTIVE. To describe emergency department visits for adverse drug events from cough and cold medications in children. METHODS. Emergency department visits for adverse drug events attributed to cough and cold medications among children aged <12 years were identified from a nationally representative stratified probability sample of 63 US emergency departments from January 1, 2004, through December 31, 2005. RESULTS. Annually, an estimated 7091 patients aged <12 years were treated in emergency departments for adverse drug events from cough and cold medications, accounting for 5.7% of emergency department visits for all medications in this age group. Most visits were for children aged 2 to 5 years (64%). Unsupervised ingestions accounted for 66% of estimated emergency department visits, which was significantly higher than unsupervised ingestions of other medications (47%), and most of these ingestions involved children aged 2 to 5 years (77%). Most children did not require admission or extended observation (93%). CONCLUSIONS. Timely national surveillance data can help target education, enforcement, and engineering strategies for reducing adverse events from cough and cold medications among children. Engineering innovations could be particularly helpful in addressing unsupervised ingestions, which is the most frequent cause of adverse events. These innovations could be applicable to other childrens medications.

Emergency department visits for overdoses of acetaminophen-containing products.

BACKGROUND Limited national data on the circumstances of acetaminophen overdoses have hindered identification and implementation of prevention strategies. PURPOSE To estimate the frequency of and characterize risks for emergency department visits for acetaminophen overdoses that were not related to abuse in the U.S. METHODS Data were collected from two components of the National Electronic Injury Surveillance System from January 1, 2006, through December 31, 2007, and analyzed from 2009 to 2010 to estimate the annual number of emergency department visits for non-abuse-related acetaminophen overdose by patient demographics, treatments, and type and amount of acetaminophen-containing product ingested. RESULTS There were an estimated 78,414 emergency department visits (95% CI=63655, 93172) annually for non-abuse-related overdoses of acetaminophen-containing products. Most emergency department visits for acetaminophen overdose were for self-directed violence (69.8%, 95% CI=66.4%, 73.2%), with the highest rate among patients aged 15-24 years (46.4 per 100,000 individuals per year). Unsupervised ingestions by children aged <6 years accounted for 13.4% (95% CI=11.0%, 15.9%) of visits for acetaminophen overdoses (42.5 per 100,000 individuals per year). Therapeutic misadventures accounted for 16.7% (95% CI=14.0%, 19.5%) of visits and most involved overuse for medicinal effects (56.1%, 95% CI=50.6%, 61.6%) rather than use of multiple acetaminophen-containing products or dose confusion. CONCLUSIONS Non-abuse-related overdoses of acetaminophen products lead to many emergency department visits each year, particularly emergency department visits for self-directed violence. Acetaminophen overdose prevention efforts will likely need to be multidimensional.

National Estimates of Emergency Department Visits for Hemorrhage-Related Adverse Events From Clopidogrel Plus Aspirin and From Warfarin

BACKGROUND Dual antiplatelet therapy (DAT) with clopidogrel plus aspirin is a well-established antithrombotic strategy, with hemorrhage being the chief adverse event (AE) of concern. Outside of clinical trials, few published data describe the magnitude and nature of hemorrhage-related AEs from DAT. METHODS To estimate the numbers and rates of emergency department (ED) visits for hemorrhage-related AEs (hemorrhage or evaluation for potential hemorrhage) from DAT in the United States and put them in the context of those from warfarin, we analyzed AEs from the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance project, 2006-2008, and outpatient prescribing from the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey, 2006-2007. RESULTS Based on 384 cases, there were an estimated 7654 (95% confidence interval [CI], 3325-11 983) ED visits annually for hemorrhage-related AEs from DAT compared with 2926 cases and an estimated 60 575 (36 117-85 033) ED visits from warfarin. Approximately 60% of ED visits for DAT consisted of epistaxis or other minor hemorrhages (eg, bleeding from small cuts). The risk of hospitalization for ED visits involving acute hemorrhages was not significantly different between DAT and warfarin (risk ratio, 0.73; 95% CI, 0.38-1.08). The estimated rate of ED visits involving acute hemorrhages from DAT was 1.2 per 1000 outpatient prescription visits vs 2.5 per 1000 outpatient prescription visits for warfarin (risk ratio, 0.49; 95% CI, 0.15-0.83). CONCLUSIONS These findings indicate that the acute hemorrhagic risk with DAT is clinically significant and reinforce the importance of practitioners and patients recognizing and anticipating this risk.