Emily C. O'Brien

The ORBIT bleeding score: a simple bedside score to assess bleeding risk in atrial fibrillation

Background Therapeutic decisions in atrial fibrillation (AF) are often influenced by assessment of bleeding risk. However, existing bleeding risk scores have limitations. Objectives We sought to develop and validate a novel bleeding risk score using routinely available clinical information to predict major bleeding in a large, community-based AF population. Methods We analysed data from Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF), a prospective registry that enrolled incident and prevalent AF patients at 176 US sites. Using Cox proportional hazards regression, we identified factors independently associated with major bleeding among patients taking oral anticoagulation (OAC) over a median follow-up of 2 years (interquartile range = 1.6–2.5). We also created a numerical bedside risk score that included the five most predictive risk factors weighted according to their strength of association with major bleeding. The predictive performance of the full model, the simple five-item score, and two existing risk scores (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile INR, elderly, drugs/alcohol concomitantly, HAS-BLED, and anticoagulation and risk factors in atrial fibrillation, ATRIA) were then assessed in both the ORBIT-AF cohort and a separate clinical trial population, Rivaroxaban Once-daily oral direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation (ROCKET-AF). Results Among 7411 ORBIT-AF patients taking OAC, the rate of major bleeding was 4.0/100 person-years. The full continuous model (12 variables) and five-factor ORBIT risk score (older age [75+ years], reduced haemoglobin/haematocrit/history of anaemia, bleeding history, insufficient kidney function, and treatment with antiplatelet) both had good ability to identify those who bled vs. not (C-index 0.69 and 0.67, respectively). These scores both had similar discrimination, but markedly better calibration when compared with the HAS-BLED and ATRIA scores in an external validation population from the ROCKET-AF trial. Conclusions The five-element ORBIT bleeding risk score had better ability to predict major bleeding in AF patients when compared with HAS-BLED and ATRIA risk scores. The ORBIT risk score can provide a simple, easily remembered tool to support clinical decision making.

Prehospital Notification by Emergency Medical Services Reduces Delays in Stroke Evaluation Findings From the North Carolina Stroke Care Collaborative

Background and Purpose— Individuals with stroke-like symptoms are recommended to receive rapid diagnostic evaluation. Emergency medical services (EMS) transport, compared with private modes, and hospital notification before arrival may reduce delays in evaluation. This study estimated associations between hospital arrival modes (EMS or private and with or without EMS prenotification) and times for completion and interpretation of initial brain imaging in patients with presumed stroke. Methods— Among patients with suspected stroke identified and enrolled by the North Carolina Stroke Care Collaborative registry in 2008 to 2009, we analyzed data on arrival modes, meeting recommended targets for brain imaging completion and interpretation times (<25 minutes and <45 minutes since hospital arrival, respectively) and patient- and hospital-level characteristics. We used modified Poisson regression to estimate adjusted risk ratios and 95% CIs. Results— Of 13 894 eligible patients, 21% had their brain imaging completed and 23% had their brain imaging interpreted by a physician within target times. Arrival by EMS (versus private transport) was associated with both brain imaging completed within 25 minutes of arrival (EMS with prenotification: risk ratio, 3.0; 95% CI, 2.1 to 4.1; EMS without prenotification: risk ratio, 1.9; 95% CI, 1.6 to 2.3) and brain imaging interpreted within 45 minutes (EMS with prenotification: risk ratio, 2.7; 95% CI, 2.3 to 3.3; EMS without prenotification: risk ratio, 1.7; 95% CI, 1.4 to 2.1). Conclusions— Patients with presumed stroke arriving to the hospital by EMS were more likely to receive brain imaging and have it interpreted by a physician in a timely manner than those arriving by private transport. Moreover, EMS arrivals with hospital prenotification experienced the most rapid evaluation.

Association of Preceding Antithrombotic Treatment With Acute Ischemic Stroke Severity and In-Hospital Outcomes Among Patients With Atrial Fibrillation

Importance Antithrombotic therapies are known to prevent stroke for patients with atrial fibrillation (AF) but are often underused in community practice. Objectives To examine the prevalence of patients with acute ischemic stroke with known history of AF who were not receiving guideline-recommended antithrombotic treatment before stroke and to determine the association of preceding antithrombotic therapy with stroke severity and in-hospital outcomes. Design, Setting, and Participants Retrospective observational study of 94 474 patients with acute ischemic stroke and known history of AF admitted from October 2012 through March 2015 to 1622 hospitals participating in the Get With the Guidelines–Stroke program. Exposures Antithrombotic therapy before stroke. Main Outcomes and Measures Stroke severity as measured by the National Institutes of Health Stroke Scale (NIHSS; range of 0-42, with a higher score indicating greater stroke severity and a score ≥16 indicating moderate or severe stroke), and in-hospital mortality. Results Of 94 474 patients (mean [SD] age, 79.9 [11.0] years; 57.0% women), 7176 (7.6%) were receiving therapeutic warfarin (international normalized ratio [INR] ≥2) and 8290 (8.8%) were receiving non–vitamin K antagonist oral anticoagulants (NOACs) preceding the stroke. A total of 79 008 patients (83.6%) were not receiving therapeutic anticoagulation; 12 751 (13.5%) had subtherapeutic warfarin anticoagulation (INR <2) at the time of stroke, 37 674 (39.9%) were receiving antiplatelet therapy only, and 28 583 (30.3%) were not receiving any antithrombotic treatment. Among 91 155 high-risk patients (prestroke CHA2DS2-VASc score ≥2), 76 071 (83.5%) were not receiving therapeutic warfarin or NOACs before stroke. The unadjusted rates of moderate or severe stroke were lower among patients receiving therapeutic warfarin (15.8% [95% CI, 14.8%-16.7%]) and NOACs (17.5% [95% CI, 16.6%-18.4%]) than among those receiving no antithrombotic therapy (27.1% [95% CI, 26.6%-27.7%]), antiplatelet therapy only (24.8% [95% CI, 24.3%-25.3%]), or subtherapeutic warfarin (25.8% [95% CI, 25.0%-26.6%]); unadjusted rates of in-hospital mortality also were lower for those receiving therapeutic warfarin (6.4% [95% CI, 5.8%-7.0%]) and NOACs (6.3% [95% CI, 5.7%-6.8%]) compared with those receiving no antithrombotic therapy (9.3% [95% CI, 8.9%-9.6%]), antiplatelet therapy only (8.1% [95% CI, 7.8%-8.3%]), or subtherapeutic warfarin (8.8% [95% CI, 8.3%-9.3%]). After adjusting for potential confounders, compared with no antithrombotic treatment, preceding use of therapeutic warfarin, NOACs, or antiplatelet therapy was associated with lower odds of moderate or severe stroke (adjusted odds ratio [95% CI], 0.56 [0.51-0.60], 0.65 [0.61-0.71], and 0.88 [0.84-0.92], respectively) and in-hospital mortality (adjusted odds ratio [95% CI], 0.75 [0.67-0.85], 0.79 [0.72-0.88], and 0.83 [0.78-0.88], respectively). Conclusions and Relevance Among patients with atrial fibrillation who had experienced an acute ischemic stroke, inadequate therapeutic anticoagulation preceding the stroke was prevalent. Therapeutic anticoagulation was associated with lower odds of moderate or severe stroke and lower odds of in-hospital mortality.

Effects of Left Ventricular Assist Device Support on Biomarkers of Cardiovascular Stress, Fibrosis, Fluid Homeostasis, Inflammation, and Renal Injury

OBJECTIVES The purpose of this study was to examine changes in a broad panel of biomarkers following left ventricular assist device (LVAD) support in advanced heart failure (HF). BACKGROUND LVAD therapy mechanically unloads the failing heart and may result in reversal of certain aspects of the end-stage HF phenotype. Changes in markers of myocardial stress, fibrosis, inflammation, fluid homeostasis, and renal injury in this setting are unknown. METHODS Amino-terminal pro-B-type natriuretic peptide (NT-proBNP), galectin-3, ST2, copeptin, growth differentiation factor (GDF)-15, C-reactive protein (CRP), and neutrophil gelatinase associated lipocalin (NGAL) levels were measured in frozen plasma collected from 37 individuals prior to continuous flow LVAD implantation and a median of 136 (interquartile range: 94 to 180) days after implantation. RESULTS The median age of patients was 68 years old. LVAD therapy was associated with significant decreases in NT-proBNP (3,093 to 2,090 pg/ml; p = 0.02), ST2 (67.5 to 45.2 ng/ml, p <0.01), galectin-3 (24.7 to 22.0 ng/ml; p = 0.04), GDF-15 (3,232 to 2,613 ng/l;p <0.001), hs-CRP (22.4 to 11.9 mg/l; p = 0.01), and copeptin (103 to 94 pmol/l; p = 0.003) but not NGAL (132 to 135 ng/ml; p = 0.06). Despite improvement over time, absolute values of each biomarker remained extremely abnormal. Greater reductions in biomarkers were noted in individuals with >25% decrease in NT-proBNP concentrations but reached statistical significance only in the case of galectin-3 (p = 0.01). CONCLUSIONS The biomarker profile in patients after LVAD placement improves but nonetheless remains significantly abnormal. Our results suggest the need for targeted therapeutic interventions to mitigate such abnormalities and potentially increase rates of myocardial recovery.

Compliance With Acute Stroke Care Quality Measures in Hospitals With and Without Primary Stroke Center Certification: The North Carolina Stroke Care Collaborative

Background Organized stroke care is associated with improved outcomes. Data are limited on differences in changes in the quality of acute stroke care at The Joint Commission–certified Primary Stroke Centers (PSCs) versus non‐PSCs over time. Methods and Results We compared compliance with the Joint Commissions 10 acute stroke care performance measures and defect‐free care in PSCs and non‐PSCs participating in the Registry of the North Carolina Stroke Care Collaborative from January 2005 through February 2010. We included 29 654 cases presenting at 47 hospitals—10 PSCs, 8 preparing for certification, and 29 non‐PSCs—representing 43% of North Carolinas non–Veterans Affairs, acute care hospitals. Using a non‐PSC referent, odds ratios and 95% CIs were calculated using logistic regression and generalized estimating equations accounting for clustering of cases within hospitals. Time trends were presented graphically using simple linear regression. Performance measure compliance increased for all measures for all 3 groups in 2005–2010, with the exception of discharge on antithrombotics, which remained consistently high. PSCs and hospitals preparing for certification had better compliance with all but 2 performance measures compared with non‐PSCs (each P<0.01). Defect‐free care was delivered most consistently at hospitals preparing for certification (52.8%), followed by PSCs (45.0%) and non‐PSCs (21.9%). Between 2005 and 2010, PSCs and hospitals preparing for certification had a higher average annual percent increase in the provision of defect‐free care (P=0.01 and 0.04, respectively) compared with non‐PSCs. Conclusions PSC certification is associated with an overall improvement in the quality of stroke care in North Carolina; however, room for improvement remains.

Ventricular Conduction and Long-Term Heart Failure Outcomes and Mortality in African Americans: Insights From the Jackson Heart Study

Background—QRS prolongation is associated with adverse outcomes in mostly white populations, but its clinical significance is not well established for other groups. We investigated the association between QRS duration and mortality in African Americans. Methods and Results—We analyzed data from 5146 African Americans in the Jackson Heart Study stratified by QRS duration on baseline 12-lead ECG. We defined QRS prolongation as QRS≥100 ms. We assessed the association between QRS duration and all-cause mortality using Cox proportional hazards models and reported the cumulative incidence of heart failure hospitalization. We identified factors associated with the development of QRS prolongation in patients with normal baseline QRS. At baseline, 30% (n=1528) of participants had QRS prolongation. The cumulative incidences of mortality and heart failure hospitalization were greater with versus without baseline QRS prolongation: 12.6% (95% confidence interval [CI], 11.0–14.4) versus 7.1% (95% CI, 6.3–8.0) and 8.2% (95% CI, 6.9–9.7) versus 4.4% (95% CI, 3.7–5.1), respectively. After risk adjustment, QRS prolongation was associated with increased mortality (hazard ratio, 1.27; 95% CI, 1.03–1.56; P=0.02). There was a linear relationship between QRS duration and mortality (hazard ratio per 10 ms increase, 1.06; 95% CI, 1.01–1.12). Older age, male sex, prior myocardial infarction, lower ejection fraction, left ventricular hypertrophy, and left ventricular dilatation were associated with the development of QRS prolongation. Conclusions—QRS prolongation in African Americans was associated with increased mortality and heart failure hospitalization. Factors associated with developing QRS prolongation included age, male sex, prior myocardial infarction, and left ventricular structural abnormalities.

Clinical Effectiveness of Statin Therapy after Ischemic Stroke: Primary Results from the Statin Therapeutic Area of the Patient-Centered Research into Outcomes Stroke Patients Prefer and Effectiveness Research (PROSPER) Study

Background— In patients with ischemic stroke, data on the real‐world effectiveness of statin therapy for clinical and patient‐centered outcomes are needed to better inform shared decision making. Methods and Results— Patient‐Centered Research Into Outcomes Stroke Patients Prefer and Effectiveness Research (PROSPER) is a Patient‐Centered Outcomes Research Institute‐funded research program designed with stroke survivors to evaluate the effectiveness of poststroke therapies. We linked data on patients ≥65 years of age enrolled in the Get With The Guidelines‐Stroke Registry to Medicare claims. Two‐year to postdischarge outcomes of those discharged on a statin versus not on a statin were adjusted through inverse probability weighting. Our coprimary outcomes were major adverse cardiovascular events and home time (days alive and out of a hospital or skilled nursing facility). Secondary outcomes included all‐cause mortality, all‐cause readmission, cardiovascular readmission, and hemorrhagic stroke. From 2007 to 2011, 77‐468 patients who were not taking statins at the time of admission were hospitalized with ischemic stroke; of these, 71% were discharged on statin therapy. After adjustment, statin therapy at discharge was associated with a lower hazard of major adverse cardiovascular events (hazard ratio, 0.91; 95% confidence interval, 0.87‐0.94), 28 more home‐time days after discharge (P<0.001), and lower all‐cause mortality and readmission. Statin therapy at discharge was not associated with increased risk of hemorrhagic stroke (hazard ratio, 0.94; 95% confidence interval, 0.72‐1.23). Among statin‐treated patients, 31% received a high‐intensity dose; after risk adjustment, these patients had outcomes similar to those of recipients of moderate‐intensity statin. Conclusion— In older ischemic stroke patients who were not taking statins at the time of admission, discharge statin therapy was associated with lower risk of major adverse cardiovascular events and nearly 1 month more home time during the 2‐year period after hospitalization.

Do patients treated at academic hospitals have better longitudinal outcomes after admission for non–ST-elevation myocardial infarction?

BACKGROUND Prior studies have found that academic hospitals provide more consistent use of guideline-recommended therapies in patients with non-ST-segment myocardial infarction (NSTEMI) compared with nonacademic centers, yet it is unclear whether these care differences translate into longer-term outcome differences. METHODS Using data from the CRUSADE Registry linked to Center for Medicare & Medicaid Services claims, we compared 30-day and 1-year all-cause mortality among 12,194 older patients with NSTEMI (age ≥65 years) treated at 103 academic centers and 28,335 patients treated at 302 nonacademic centers from February 2003 to December 2006. Outcomes were first adjusted for clinical characteristics, followed by adjustment for hospital performance, on 13 acute and discharge guideline-recommended therapies using a shared frailty model (an extension of the Cox proportional hazard model). RESULTS Compared with older patients with NSTEMI treated at nonacademic hospitals, those treated at academic hospitals had greater and more consistent use of evidence-based acute and discharge therapies, were more likely to receive in-hospital revascularization (61.1% vs 54.2%; P < .0001), and had modestly lower risk-adjusted 30-day mortality after adjustment for patient-level clinical characteristics (8.9% vs 10.2%, adjusted hazard ratio [HR] 0.89, 95% CI 0.80-0.99). These differences were attenuated (HR 0.94, 95% CI 0.83-1.02) after further adjustment for hospital delivery of evidence-based treatments, yet did not persist out to 1 year (unadjusted HR 0.92, 95% CI 0.84-1.01, P = .089). CONCLUSIONS Patients with NSTEMI treated at academic centers are more likely to receive guideline-recommended therapies and had modestly better 30-day outcomes. Nevertheless, these differences do not persist out to 1 year.

Clinical Characteristics, Oral Anticoagulation Patterns, and Outcomes of Medicaid Patients With Atrial Fibrillation: Insights From the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT‐AF I) Registry

Background Whereas insurance status has been previously associated with care patterns, little is currently known about the association between Medicaid insurance and the clinical characteristics, treatment, or outcomes of patients with atrial fibrillation (AF). Methods and Results We used data from adults with AF enrolled in the Outcomes Registry for Better Informed Treatment of AF (ORBIT‐AF), a national outpatient registry conducted at 176 community, multispecialty sites. The primary outcome of interest was the proportion of patients prescribed any oral anticoagulation (OAC; warfarin or novel oral anticoagulants [NOAC]). Secondary outcomes of interest included the proportion of patients prescribed NOACs (dabigatran or rivaroxaban); time in therapeutic range (TTR) for warfarin users, all‐cause mortality, stroke/systemic embolism, and major bleed. Of 10 133 patients, N=470 (4.6%) had Medicaid insurance. Medicaid patients were similarly likely to receive OAC at baseline (72.8% vs 76.3%; unadjusted P=0.079), but less likely to receive NOAC at baseline or follow‐up (12.1% vs 16.3%; unadjusted P=0.019). After risk adjustment, Medicaid status was associated with lower use of OAC at baseline among patients with high stroke risk (odds ratio [OR]=0.68; 95% CI=0.49, 0.94), but was not associated with OAC use overall (OR=0.82; 95% CI=0.61, 1.09). Among warfarin users, median TTR was lower among Medicaid patients (60% vs 68%; P<0.0001; adjusted TTR difference, −2.9; 95% CI=−5.7, −0.2; P=0.04). Use of an NOAC over 2 years of follow‐up was not statistically different by insurance. Compared with non‐Medicaid patients, Medicaid patients had higher unadjusted rates of mortality, stroke/systemic embolism, and major bleeding; however, these differences were attenuated following adjustment for clinical characteristics. Conclusions In a contemporary AF cohort, use of OAC overall and use of NOACs were not significantly lower among Medicaid patients relative to others. However, among warfarin users, Medicaid patients spent less time in therapeutic range compared with those with other forms of insurance.

Stroke Mortality, Clinical Presentation and Day of Arrival: The Atherosclerosis Risk in Communities (ARIC) Study

Background. Recent studies report that acute stroke patients who present to the hospital on weekends have higher rates of 28-day mortality than similar patients who arrive during the week. However, how this association is related to clinical presentation and stroke type has not been systematically investigated. Methods and Results. We examined the association between day of arrival and 28-day mortality in 929 validated stroke events in the ARIC cohort from 1987–2004. Weekend arrival was defined as any arrival time from midnight Friday until midnight Sunday. Mortality was defined as all-cause fatal events from the day of arrival through the 28th day of followup. The presence or absence of thirteen stroke signs and symptoms were obtained through medical record review for each event. Binomial logistic regression was used to estimate odds ratios and 95% confidence intervals (OR; 95% CI) for the association between weekend arrival and 28-day mortality for all stroke events and for stroke subtypes. The overall risk of 28-day mortality was 9.6% for weekday strokes and 10.1% for weekend strokes. In models controlling for patient demographics, clinical risk factors, and event year, weekend arrival was not associated with 28-day mortality (0.87; 0.51, 1.50). When stratified by stroke type, weekend arrival was not associated with increased odds of mortality for ischemic (1.17, 0.62, 2.23) or hemorrhagic (0.37; 0.11, 1.26) stroke patients. Conclusions. Presence or absence of thirteen signs and symptoms was similar for weekday patients and weekend patients when stratified by stroke type. Weekend arrival was not associated with 28-day all-cause mortality or differences in symptom presentation for strokes in this cohort.