Factors Associated With Coronary Angiography Performed Within 6 Months of Randomization to the Conservative Strategy in the ISCHEMIA Trial.

BACKGROUND: ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) did not find an overall reduction in cardiovascular events with an initial invasive versus conservative management strategy in chronic coronary disease; however, there were conservative strategy participants who underwent invasive coronary angiography early postrandomization (within 6 months). Identifying factors associated with angiography in conservative strategy participants will inform clinical decision-making in patients with chronic coronary disease. METHODS: Factors independently associated with angiography performed within 6 months of randomization were identified using Fine and Gray proportional subdistribution hazard models, including demographics, region of randomization, medical history, risk factor control, symptoms, ischemia severity, coronary anatomy based on protocol-mandated coronary computed tomography angiography, and medication use. RESULTS: Among 2591 conservative strategy participants, angiography within 6 months of randomization occurred in 8.7% (4.7% for a suspected primary end point event, 1.6% for persistent symptoms, and 2.6% due to protocol nonadherence) and was associated with the following baseline characteristics: enrollment in Europe versus Asia (hazard ratio [HR], 1.81 [95% CI, 1.14-2.86]), daily and weekly versus no angina (HR, 5.97 [95% CI, 2.78-12.86] and 2.63 [95% CI, 1.51-4.58], respectively), poor to fair versus good to excellent health status (HR, 2.02 [95% CI, 1.23-3.32]) assessed with Seattle Angina Questionnaire, and new/more frequent angina prerandomization (HR, 1.80 [95% CI, 1.34-2.40]). Baseline low-density lipoprotein cholesterol <70 mg/dL was associated with a lower risk of angiography (HR, 0.65 [95% CI, 0.46-0.91) but not baseline ischemia severity nor the presence of multivessel or proximal left anterior descending artery stenosis >70% on coronary computed tomography angiography. CONCLUSIONS: Among ISCHEMIA participants randomized to the conservative strategy, angiography within 6 months of randomization was performed in <10% of patients. It was associated with frequent or increasing baseline angina and poor quality of life but not with objective markers of disease severity. Well-controlled baseline low-density lipoprotein cholesterol was associated with a reduced likelihood of angiography. These findings point to the importance of a comprehensive assessment of symptoms and a review of guideline-directed medical therapy goals when deciding the initial treatment strategy for chronic coronary disease. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01471522.

Factors associated with coronary angiography performed within 6 months of randomization to the conservative strategy in the ISCHEMIA Trial

BACKGROUND: ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) did not find an overall reduction in cardiovascular events with an initial invasive versus conservative management strategy in chronic coronary disease; however, there were conservative strategy participants who underwent invasive coronary angiography early postrandomization (within 6 months). Identifying factors associated with angiography in conservative strategy participants will inform clinical decision-making in patients with chronic coronary disease. METHODS: Factors independently associated with angiography performed within 6 months of randomization were identified using Fine and Gray proportional subdistribution hazard models, including demographics, region of randomization, medical history, risk factor control, symptoms, ischemia severity, coronary anatomy based on protocol-mandated coronary computed tomography angiography, and medication use. RESULTS: Among 2591 conservative strategy participants, angiography within 6 months of randomization occurred in 8.7% (4.7% for a suspected primary end point event, 1.6% for persistent symptoms, and 2.6% due to protocol nonadherence) and was associated with the following baseline characteristics: enrollment in Europe versus Asia (hazard ratio [HR], 1.81 [95% CI, 1.14­2.86]), daily and weekly versus no angina (HR, 5.97 [95% CI, 2.78­12.86] and 2.63 [95% CI, 1.51­4.58], respectively), poor to fair versus good to excellent health status (HR, 2.02 [95% CI, 1.23­3.32]) assessed with Seattle Angina Questionnaire, and new/more frequent angina prerandomization (HR, 1.80 [95% CI, 1.34­2.40]). Baseline low-density lipoprotein cholesterol <70 mg/dL was associated with a lower risk of angiography (HR, 0.65 [95% CI, 0.46­0.91) but not baseline ischemia severity nor the presence of multivessel or proximal left anterior descending artery stenosis >70% on coronary computed tomography angiography. CONCLUSIONS: Among ISCHEMIA participants randomized to the conservative strategy, angiography within 6 months of randomization was performed in <10% of patients. It was associated with frequent or increasing baseline angina and poor quality of life but not with objective markers of disease severity. Well-controlled baseline low-density lipoprotein cholesterol was associated with a reduced likelihood of angiography. These findings point to the importance of a comprehensive assessment of symptoms and a review of guideline-directed medical therapy goals when deciding the initial treatment strategy for chronic coronary disease.

Effects of Long-Term Sertraline Use on Pediatric Growth and Development: The Sertraline Pediatric Registry for The Evaluation of Safety (SPRITES).

Objective: To describe the results of the Sertraline Pediatric Registry for The Evaluation of Safety (SPRITES) outcome measures of cognitive, emotional, and physical development following long-term treatment with sertraline (for up to 3 years) in children and adolescents aged 6-16 years. Methods: SPRITES was a long-term, multicenter, open-label, prospective observational study designed to compare physical and psychological development in pediatric patients exposed to sertraline (with or without psychotherapy) or psychotherapy alone in usual care settings. Data were summarized descriptively, and outcomes were evaluated using a marginal structural model. Results: Between April 2012 and September 2020, 941 patients across 44 U.S. sites participated in the study. At baseline, 695 participants were exposed to sertraline (physician prescribed) with or without psychotherapy, and 245 participants were exposed to psychotherapy alone. Of these, 432 participants (46.0%) completed the full 3-year study follow-up. No significant changes across time were found in standardized height, BRIEF (Behavior Rating Inventory of Executive Function), Trails B, and Tanner stage based on cumulative sertraline exposure or exposure since the last visit. Change in mean standardized weight across time was positively associated with both cumulative sertraline exposure (p = 0.02) and exposure since the last visit (p = 0.029). The mean changes from baseline across time in standardized weight were standard deviations of 0.02, 0.03, 0.16, and 0.17 at months 3, 6, 30, and 36, respectively. However, this finding was not observed in the mean change across time in standardized body mass index, which was not statistically significant. Conclusions: Results are consistent with normal development. Although a statistically significant finding for standardized weight was observed in comparative analyses, the magnitude of the change is small and observed at higher doses of sertraline only. No other significant differences were observed between the "sertraline" group and the "no pharmacological therapy" group on other primary outcome measures. ClinicalTrials.gov identifier: NCT01302080.

At-home testing to mitigate community transmission of SARS-CoV-2: protocol for a public health intervention with a nested prospective cohort study.

BACKGROUND: The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve as a global health crisis. Although highly effective vaccines have been developed, non-pharmaceutical interventions remain critical to controlling disease transmission. One such intervention-rapid, at-home antigen self-testing-can ease the burden associated with facility-based testing programs and improve testing access in high-risk communities. However, its impact on SARS-CoV-2 community transmission has yet to be definitively evaluated, and the socio-behavioral aspects of testing in underserved populations remain unknown. METHODS: As part of the Rapid Acceleration of Diagnostics-Underserved Populations (RADx-UP) program funded by the National Institutes of Health, we are implementing a public health intervention titled "Say Yes! COVID Test" (SYCT) involving at-home self-testing using a SARS-CoV-2 rapid antigen assay in North Carolina (Greenville, Pitt County) and Tennessee (Chattanooga City, Hamilton County). The intervention is supported by a multifaceted communication and community engagement strategy to ensure widespread awareness and uptake, particularly in marginalized communities. Participants receive test kits either through online orders or via local community distribution partners. To assess the impact of this intervention on SARS-CoV-2 transmission, we will conduct a non-randomized, ecological study using community-level outcomes. Specifically, we will evaluate trends in SARS-CoV-2 cases and hospitalizations, SARS-CoV-2 viral load in wastewater, and population mobility in each community before, during, and after the SYCT intervention. Individuals who choose to participate in SYCT will also have the option to enroll in an embedded prospective cohort substudy gathering participant-level data to evaluate behavioral determinants of at-home self-testing and socio-behavioral mechanisms of SARS-CoV-2 community transmission. DISCUSSION: This is the first large-scale, public health intervention implementing rapid, at-home SARS-CoV-2 self-testing in the United States. The program consists of a novel combination of an at-home testing program, a broad communications and community engagement strategy, an ecological study to assess impact, and a research substudy of the behavioral aspects of testing. The findings from the SYCT project will provide insights into innovative methods to mitigate viral transmission, advance the science of public health communications and community engagement, and evaluate emerging, novel assessments of community transmission of disease.

Sertraline Pediatric Registry for the Evaluation of Safety: Design and Clinical Characteristics of Pediatric Patients Prescribed Sertraline.

Objectives: To describe the study design and clinical characteristics of patients in the Sertraline Pediatric RegIstry for The Evaluation of Safety (SPRITES). Methods: SPRITES is an open-label postmarketing study of development and safety outcomes in patients aged 6 to 16 years treated with sertraline (with or without psychotherapy) compared with psychotherapy alone for up to 3 years in the United States. Baseline data included demographics and psychiatric history. Primary outcomes included measures of cognitive and emotional development (Trails B, Behavior Rating Inventory of Executive Function [BRIEF]), physical development (height and weight), and pubertal status (Tanner Stage). Data were also collected on present/lifetime risk of suicide-related events using the Columbia-Suicide Severity Rating Scale. Results: SPRITES enrolled 941 patients between the ages of 6 and 16 years. Patients' baseline mean age was 11.9 years (2.9), 57.2% were female, and 84.8% were white. Most patients (78.4%) had an anxiety disorder, and 15.6% were diagnosed with obsessive-compulsive disorder. The mean age at onset of first mental illness was 7.9 years. A higher percentage of sertraline-treated patients compared with patients who received no pharmacological treatment received prior psychotherapy (59.0% vs. 34.4%, p < 0.001), psychotropic medications for a psychiatric disorder (14.1% vs. 3.3%, p < 0.001), and other non-sertraline selective serotonin reuptake inhibitors (8.6% vs. 1.2%, p < 0.001). Most patients were moderately ill on the Clinical Global Impressions-Severity scale, and a higher (p < 0.001) percentage of sertraline-treated patients had a moderate-to-severe mental illness score compared with the no pharmacological treatment group (73.0% vs. 57.8%, respectively). Although patients at high and imminent risk of a suicidal event were excluded at study entry, the sertraline-treated patients reported higher levels of lifetime suicidal behavior compared with patients treated with no pharmacological treatment (5.8% vs. 2.5%, p = 0.039). Conclusions: Baseline data from this nonrandomized observational study suggest that patients prescribed sertraline are reflective of a more mentally ill study population compared with patients receiving psychotherapy. ClinicalTrials.gov identifier: NCT01302080.

Management of Coronary Disease in Patients with Advanced Kidney Disease.

BACKGROUND: Clinical trials that have assessed the effect of revascularization in patients with stable coronary disease have routinely excluded those with advanced chronic kidney disease. METHODS: We randomly assigned 777 patients with advanced kidney disease and moderate or severe ischemia on stress testing to be treated with an initial invasive strategy consisting of coronary angiography and revascularization (if appropriate) added to medical therapy or an initial conservative strategy consisting of medical therapy alone and angiography reserved for those in whom medical therapy had failed. The primary outcome was a composite of death or nonfatal myocardial infarction. A key secondary outcome was a composite of death, nonfatal myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. RESULTS: At a median follow-up of 2.2 years, a primary outcome event had occurred in 123 patients in the invasive-strategy group and in 129 patients in the conservative-strategy group (estimated 3-year event rate, 36.4% vs. 36.7%; adjusted hazard ratio, 1.01; 95% confidence interval [CI], 0.79 to 1.29; P = 0.95). Results for the key secondary outcome were similar (38.5% vs. 39.7%; hazard ratio, 1.01; 95% CI, 0.79 to 1.29). The invasive strategy was associated with a higher incidence of stroke than the conservative strategy (hazard ratio, 3.76; 95% CI, 1.52 to 9.32; P = 0.004) and with a higher incidence of death or initiation of dialysis (hazard ratio, 1.48; 95% CI, 1.04 to 2.11; P = 0.03). CONCLUSIONS: Among patients with stable coronary disease, advanced chronic kidney disease, and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of death or nonfatal myocardial infarction. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA-CKD ClinicalTrials.gov number, NCT01985360.).

What is the best ST-segment recovery parameter to predict clinical outcome and myocardial infarct size? Amplitude, speed, and completeness of ST-segment recovery after primary percutaneous coronary intervention for ST-segment elevation myocardial infarction.

AIMS: ST-segment recovery (STR) is a strong mechanistic correlate of infarct size (IS) and outcome in ST-segment elevation myocardial infarction (STEMI). Characterizing measures of speed, amplitude, and completeness of STR may extend the use of this noninvasive biomarker. METHODS AND RESULTS: Core laboratory continuous 24-h 12-lead Holter ECG monitoring, IS by single-photon emission computed tomography (SPECT), and 30-day mortality of 2 clinical trials of primary percutaneous coronary intervention in STEMI were combined. Multiple ST measures (STR at last contrast injection (LC) measured from peak value; 30, 60, 90, 120, and 240min, residual deviation; time to steady ST recovery; and the 3-h area under the time trend curve [ST-AUC] from LC) were univariably correlated with IS and predictive of mortality. After multivariable adjustment for ST-parameters and GRACE risk factors, STR at 240min remained an additive predictor of mortality. Early STR, residual deviation, and ST-AUC remained associated with IS. CONCLUSIONS: Multiple parameters that quantify the speed, amplitude, and completeness of STR predict mortality and correlate with IS.

Comparison of Clinical Characteristics and Outcomes of Patients With Versus Without Diabetes Mellitus and With Versus Without Angina Pectoris (from the Duke Databank for Cardiovascular Disease).

Angina pectoris (AP) has different prognostic implications in various populations. Patients with diabetes mellitus (DM) may experience neuropathy such that AP may not be perceived in the setting of coronary artery disease (CAD). The prognostic utility of AP in DM patients with CAD is not well known. We analyzed patients with CAD who underwent coronary angiography at Duke University from 2002 to 2011 and compared patients with and without AP within the previous 6 weeks stratified by DM status. We used multivariable Cox regression to assess the association between AP and the outcomes of cardiovascular (CV) hospitalization/revascularization, all-cause mortality/myocardial infarction/revascularization, and all-cause mortality. Of 17,211 patients with CAD, 5,284 (31%) had DM and AP was present in 69% of DM and 67% of non-DM. After risk adjustment, the risk of CV hospitalization/revascularization and all-cause mortality/myocardial infarction/revascularization in patients with and without AP was similar regardless of DM status (all p ≥0.05). In patients with or without DM, AP was associated with lower all-cause mortality compared with no AP (adjusted hazard ratio 0.89, 95% confidence interval 0.82 to 0.97, p = 0.005 for DM patients). The relation between AP status and clinical outcomes was not dependent on DM status (all interaction p >0.10). In conclusion, in patients with CAD, AP was associated with similar risk for CV hospitalization and revascularization and lower all-cause mortality compared with patients without AP regardless of DM status. Future studies are needed to assess whether these findings are related to increased severity of disease in those without AP or whether AP leads to differential management that improves survival.

Race and Sex Differences in QRS Interval and Associated Outcome Among Patients with Left Ventricular Systolic Dysfunction.

BACKGROUND: Prolonged QRS duration is associated with increased mortality among heart failure patients, but race or sex differences in QRS duration and associated effect on outcomes are unknown. METHODS AND RESULTS: We investigated QRS duration and morphology among 2463 black and white patients with heart failure and left ventricular ejection fraction ≤35% who underwent coronary angiography and 12-lead electrocardiography at Duke University Hospital from 1995 through 2011. We used multivariable Cox regression models to assess the relationship between QRS duration and all-cause mortality and investigate race-QRS and sex-QRS duration interaction. Median QRS duration was 105 ms (interquartile range [IQR], 92-132) with variation by race and sex (P<0.001). QRS duration was longest in white men (111 ms; IQR, 98-139) followed by white women (108 ms; IQR, 92-140), black men (100 ms; IQR, 91-120), and black women (94 ms; IQR, 86-118). Left bundle branch block was more common in women than men (24% vs 14%) and in white (21%) versus black individuals (12%). In black patients, there was a 16% increase in risk of mortality for every 10 ms increase in QRS duration up to 112 ms (hazard ratio, 1.16; 95% CI, 1.07, 1.25) that was not present among white patients (interaction, P=0.06). CONCLUSIONS: Black individuals with heart failure had a shorter QRS duration and more often had non-left bundle branch block morphology than white patients. Women had left bundle branch block more commonly than men. Among black patients, modest QRS prolongation was associated with increased mortality.

Antianginal medications and long-term outcomes after elective catheterization in patients with coronary artery disease.

BACKGROUND: Antianginal medications are a class I recommendation by the American College of Cardiology/American Heart Association guidelines for stable ischemic heart disease. We sought to better understand guidance in drug selection and real-life outcomes of antianginal medication use. HYPOTHESIS: In patients with stable ischemic heart disease, antianginal medications lower mortality. METHODS: We evaluated 5608 patients with obstructive coronary artery disease (CAD) on elective cardiac catheterization with follow-up through self-administered questionnaires. Patients were classified as being prescribed a particular medication if they received that medication at index catheterization, or within 3 months postcatheterization. The association between antianginal medication use and outcomes was evaluated using Cox proportional hazards models. RESULTS: Compared with the 11% not prescribed any antianginal medication, patients prescribed antianginal medication were more likely to be older and female; have a history of hypertension, diabetes mellitus, peripheral vascular disease, or 3-vessel CAD; have lower adjusted mortality (hazard ratio [HR]: 0.75, 95% confidence interval [CI]: 0.63-0.89); and experience mortality or myocardial infarction (HR: 0.83, 95% CI: 0.71-0.98). Compared with patients not taking ß-blockers (17%), those taking ß-blockers had a lower risk of mortality (HR: 0.76, 95% CI: 0.66-0.88). Patients prescribed calcium channel blockers or long-acting nitrates had a higher risk of mortality compared with nonusers (HR: 1.16, 95% CI: 1.04-1.29; HR: 1.20, 95% CI: 1.08-1.34; respectively). CONCLUSIONS: Antianginal medications are not universally prescribed among obstructive CAD patients; nonuse was associated with higher mortality. For CAD patients with or without prior myocardial infarction, ß-blockers were associated with improved long-term survival.

Everolimus versus sunitinib for patients with metastatic non-clear cell renal cell carcinoma (ASPEN): a multicentre, open-label, randomised phase 2 trial.

BACKGROUND: Non-clear cell renal cell carcinomas are histologically and genetically diverse kidney cancers with variable prognoses, and their optimum initial treatment is unknown. We aimed to compare the mTOR inhibitor everolimus and the VEGF receptor inhibitor sunitinib in patients with non-clear cell renal cell carcinoma. METHODS: We enrolled patients with metastatic papillary, chromophobe, or unclassified non-clear cell renal cell carcinoma with no history of previous systemic treatment. Patients were randomly assigned (1:1) to receive everolimus (10 mg/day) or sunitinib (50 mg/day; 6-week cycles of 4 weeks with treatment followed by 2 weeks without treatment) administered orally until disease progression or unacceptable toxicity. Randomisation was stratified by Memorial Sloan Kettering Cancer Center risk group and papillary histology. The primary endpoint was progression-free survival in the intention-to-treat population using the RECIST 1.1 criteria. Safety was assessed in all patients who were randomly assigned to treatment. This study is registered with ClinicalTrials.gov, number NCT01108445. FINDINGS: Between Sept 23, 2010, and Oct 28, 2013, 108 patients were randomly assigned to receive either sunitinib (n=51) or everolimus (n=57). As of December, 2014, 87 progression-free survival events had occurred with two remaining active patients, and the trial was closed for the primary analysis. Sunitinib significantly increased progression-free survival compared with everolimus (8·3 months [80% CI 5·8-11·4] vs 5·6 months [5·5-6·0]; hazard ratio 1·41 [80% CI 1·03-1·92]; p=0·16), although heterogeneity of the treatment effect was noted on the basis of histological subtypes and prognostic risk groups. No unexpected toxic effects were reported, and the most common grade 3-4 adverse events were hypertension (12 [24%] of 51 patients in the sunitinib group vs one [2%] of 57 patients in the everolimus group), infection (six [12%] vs four [7%]), diarrhoea (five [10%] vs one [2%]), pneumonitis (none vs five [9%]), stomatitis (none vs five [9%]), and hand-foot syndrome (four [8%] vs none). INTERPRETATION: In patients with metastatic non-clear cell renal cell carcinoma, sunitinib improved progression-free survival compared with everolimus. Future trials of novel agents should account for heterogeneity in disease outcomes based on genetic, histological, and prognostic factors. FUNDING: Novartis and Pfizer.

Uso de agentes antiarrítmicos y resultados clínicos en pacientes añosos con fibrilación auricular y enfermedad coronaria concomitante

Objetivo: la fibrilación auricular (FA) y la enfermedad coronaria (EC) son comunes en los pacientes añosos. En este estudio nos propusimos describir el uso de agentes antiarrítmicos (AAA) y los resultados clínicos en estos pacientes. Métodos y resultados: se analizó el tratamiento con AAA y los resultados observados en 1.738 pacientes mayores (edad ³65) con FA y EC registrados en el Banco de Datos para Enfermedad Cardiovascular de Duke. Los resultados primarios fueron mortalidad y rehospitalización al año y a los cinco años. En términos generales, 35% de los pacientes recibían un AAA al inicio, 43% eran mujeres y 85% eran blancos. Fueron frecuentes los antecedentes de infarto de miocardio (IM, 31%) e insuficiencia cardíaca (41%). La amiodarona era el AAA más frecuente (21%), seguida de agentes de Clase III pura (sotalol 6,3%, dofetilida 2,2%). La persistencia de los AAA fue baja (35% al año). Luego del ajuste, el uso de AAA al inicio no se asoció con la mortalidad al año (cociente de riesgo ajustado (HR) 1,23, intervalo de confianza (IC) 95%: 0,94-1,60) o con la mortalidad cardiovascular (HR ajustado 1,27, IC 95% 0,90-1,80). Sin embargo, el uso de AAA sí se asoció con un aumento de la rehospitalización por todas las causas (HR ajustado 1,20, IC 95%: 1,03-1,39) y rehospitalización cardiovascular (HR ajustado 1,20, IC 95% 1,01-1,43) al año. Esta asociación no se mantiene a los cinco años; sin embargo, estos pacientes tuvieron un elevado riesgo de muerte (55% para los >75 años y que recibían AAA) y rehospitalización (87% para aquellos >75 años que recibían AAA) a los cinco años. Conclusiones: en pacientes añosos que padecen FA y EC, la terapia antiarrítmica se acompañó de aumento de la rehospitalización al año. En términos generales, estos pacientes presentan un alto riesgo de internación y muerte a largo plazo. Se necesitan desarrollar terapias más seguras, mejor toleradas y que brinden un control de los síntomas más eficaz en esta población de alto riesgo.

Predictors of long-term clinical endpoints in patients with refractory angina.

BACKGROUND: Clinical outcomes in patients with refractory angina (RA) are poorly characterized and variably described. Using the Duke Database for Cardiovascular Disease (DDCD), we explored characteristics that drive clinical endpoints in patients with class II to IV angina stabilized on medical therapy. METHODS AND RESULTS: We explored clinical endpoints and associated costs of patients who underwent catheterization at Duke University Medical Center from 1997 to 2010 for evaluation of coronary artery disease (CAD) and were found to have advanced CAD ineligible for additional revascularization, and were clinically stable for a minimum of 60 days. Of 77 257 cardiac catheterizations performed, 1908 patients met entry criteria. The 3-year incidence of death; cardiac rehospitalization; and a composite of death, myocardial infarction, stroke, cardiac rehospitalization, and revascularization were 13.0%, 43.5%, and 52.2%, respectively. Predictors of mortality included age, ejection fraction (EF), low body mass index, multivessel CAD, low heart rate, diabetes, diastolic blood pressure, history of coronary artery bypass graft surgery, cigarette smoking, history of congestive heart failure (CHF), and race. Multivessel CAD, EF<45%, and history of CHF increased risk of mortality; angina class and prior revascularization did not. Total rehospitalization costs over a 3-year period per patient were $10 185 (95% CI 8458, 11912) in 2012 US dollars. CONCLUSIONS: Clinically stable patients with RA who are medically managed have a modest mortality, but a high incidence of hospitalization and resource use over 3 years. These findings point to the need for novel therapies aimed at symptom mitigation in this population and their potential impact on health care utilization and costs.

Clinical outcome as a function of the PR-interval-there is virtue in moderation: data from the Duke Databank for cardiovascular disease.

AIMS: Recently, a U-shaped association between PR-interval and the risk of developing atrial fibrillation was described, with higher risk in patients with long and short PR-intervals. Little is known regarding the association of PR-interval duration and mortality. The objective of the current study was to explore the relationship between PR-interval and major cardiovascular outcomes in patients with known coronary heart disease. METHODS AND RESULTS: Patients in sinus rhythm, undergoing coronary angiography at Duke University Medical Center between 1989 and 2010, who had significant stenosis in at least one native coronary artery, were included. Patients with arrhythmia, second- or third-degree AV-block, QRS > 120 ms were excluded. A total of 9,637 patients were included (median age 63, IQR 55-71 years, 67% men). After adjustment for relevant covariates, the risk of a CV event increased with a decreasing PR-interval (10 ms decrements) for PR-interval values <162 ms (all-cause mortality; HR 1.057, 95% CI 1.019-1.096, P = 0.0030, composite of death or stroke; HR 1.047, 95% CI 1.011-1.085, P = 0.0095 and composite of cardiovascular death or cardiovascular rehospitalization; HR 1.032, 95% CI 1.002-1.063, P = 0.0387). No statistically significant changes in the risk associated with PR-interval for values >162 ms were seen for any of the studied endpoints. CONCLUSION: In patients with coronary heart disease, a prolongation of the PR-interval was not independently associated with poor outcomes, but a PR-interval shorter than normal was associated with increased all-cause mortality and other major cardiovascular events.

Persistent angina pectoris in ischaemic cardiomyopathy: increased rehospitalization and major adverse cardiac events.

AIMS: The impact of refractory angina pectoris (AP) in patients with ischaemic cardiomyopathy (ICM) is unknown. We investigated the characteristics and outcomes of ICM patients with persistent AP following cardiac catheterization. METHODS AND RESULTS: Patients who underwent coronary angiography at Duke from 2000 to 2009 with an EF <40% and ICM with persistent AP were compared with similar patients without persistent AP. Persistent AP was defined by patient report of ischaemic symptoms within 1 year of index catheterization. Time-to-event was examined using Kaplan-Meier or cumulative incidence and Cox proportional hazards modelling methods for death/myocardial infarction (MI)/revascularization [i.e. major adverse cardiac events (MACE)], death/MI, death, and cardiovascular death/hospitalization. Of 965 ICM patients, 298 (31%) had persistent AP. These patients were younger and had more previous revascularization than patients without persistent AP. Both groups had high use of aspirin, beta-blockers, ACE inhibitors, and statins, but modest nitrate use. Over a median follow-up of >5 years, patients with persistent AP had increased rates of MACE, and cardiovascular death/hospitalization compared with patients without persistent AP [5-year cumulative event rates of 53% vs. 46% (P = 0.013) and 73% vs. 60% (P < 0.0001), respectively], but similar rates of death (P = 0.59) and death/MI (P = 0.50). After multivariable adjustment, persistent AP remained associated with increased MACE [hazard ratio (HR) 1.30; 95% confidence interval (CI) 1.08-1.57], and cardiovascular death/hospitalization (HR 1.36; 95% CI 1.14-1.62). CONCLUSION: Persistent AP is common despite medical therapy in patients with ICM and is independently associated with increased long-term MACE and rehospitalization. Future prospective studies of persistent AP in ICM patients are warranted.

Use of antiarrhythmic drug therapy and clinical outcomes in older patients with concomitant atrial fibrillation and coronary artery disease.

AIMS: Atrial fibrillation (AF) and coronary artery disease (CAD) are common in older patients. We aimed to describe the use of antiarrhythmic drug (AAD) therapy and clinical outcomes in these patients. METHODS AND RESULTS: We analysed AAD therapy and outcomes in 1738 older patients (age ≥65) with AF and CAD in the Duke Databank for cardiovascular disease. The primary outcomes were mortality and rehospitalization at 1 and 5 years. Overall, 35% of patients received an AAD at baseline, 43% were female and 85% were white. Prior myocardial infarction (MI, 31%) and heart failure (41%) were common. Amiodarone was the most common AAD (21%), followed by pure Class III agents (sotalol 6.3%, dofetilide 2.2%). Persistence of AAD was low (35% at 1 year). After adjustment, baseline AAD use was not associated with 1-year mortality [adjusted hazard ratio (HR) 1.23, 95% confidence interval (CI) 0.94-1.60] or cardiovascular mortality (adjusted HR 1.27, 95% CI 0.90-1.80). However, AAD use was associated with increased all-cause rehospitalization (adjusted HR 1.20, 95% CI 1.03-1.39) and cardiovascular rehospitalization (adjusted HR 1.20, 95% CI 1.01-1.43) at 1 year. This association did not persist at 5 years; however, these patients were at very high risk of death (55% for those >75 and on AAD) and all-cause rehospitalization (87% for those >75 and on AAD) at 5 years. CONCLUSIONS: In older patients with AF and CAD, antiarrhythmic therapy was associated with increased rehospitalization at 1 year. Overall, these patients are at high risk of longer-term hospitalization and death. Safer, better-tolerated, and more effective therapies for symptom control in this high-risk population are warranted.